ANALISIS JURNAL CA SERVIKS

Update On Prevention And Screening Of Cervival Cancer (Update Pada Pencegahan dan
Skrining Kanker Serviks) dan Hubungan Pemakaian Kontrasepsi Hormonal dan Non Hormonal
Dengan Kejadian Kanker Serviks di Ruang D Atas BLU, PROF, Dr, R. D. Kandau Manado.

Disusun Oleh :

Neni Rochmayati Satuhu

NPM 220112160110

FAKULTAS KEPERAWATAN

UNIVERSITAS PADJADJARAN

BANDUNG

2016
 DAFTAR ISI

BAB I PENDAHULUAN..................................................................................................... 1

BAB II ANALISIS JURNAL.............................................................................................. 3

BAB III PEMBAHASAN.................................................................................................... 9

BAB IV SIMPULAN DAN SARAN................................................................................... 11

DAFTAR PUSTAKA

LAMPIRAN JURNAL
 BAB I

PENDAHULUAN

Kanker serviks adalah penyakit akibat tumor ganas pada daerah mulut rahim sebagai

akibat dari adanya pertumbuhan jaringan yang tidak terkontrol dan merusak jaringan normal di

sekitarnya (FKUI, 1990; FKKP, 1997). Kanker serviks merupakan penyebab paling umum pada

penyakit kanker, perempuan di dunia. Penyakit kanker serviks ini merupakan penyakit terbesar

ke tiga di dunia, WHO memperkirakan bahwa setiap tahun 530.000 perempuan di seluruh dunia

mengidap kanker serviks dan 275.000 perempuan meninggal karena penyakit tersebut. (World

Journal Of Clinical Oncology, 2014).

Berdasarkan data yang diambil dari Badan Litbangkes Kementrian Kesehatan RI tahun

2013, kanker serviks merupakan penyakit kanker dengan prevalansi tertinggi di indonesia

dengan estimasi jumlah diagnosa dokter 0,8% dengan estimasi jumlah 98.692 orang. Provinsi

Kepulauan Riau, Provinsi Maluku Utara dan Provinsi D.I Yogyakarta memiliki prevalansi

kanker serviks tertinggi yaitu 1,5%.

Kanker serviks merupakan sejenis kanker yang 99,7% disebabkan oleh Human Papilloma

Virus (HPV) onkogenik, yang menyerang pada leher rahim. Kelompok yang paling beresiko

terserang penyaik kanker serviks ialah pada perempuan diatas usia 30 tahun yang memiliki

banyak anak dengan perilaku menjaga kesehatan reproduksi yang kurang.

Penyakit kanker serviks ini belum diketahui penyebabnya secara pasti, yang di duga

antara lain yaitu melakukan hubungan seksual pertamakali di bawah umur 20 tahun, pasangan

seksual dua orang atau lebih, merokok, higiene perorangan yang rendah, kemiskinan, melahirkan

anak pada usia muda, prekuensi koitus yang tinggi, peradangan, paritas lebih dari tiga dan

1
 2

adanya bahan- bahan mutagen yang di duga dapat merubah sel-sel di jaringan rahim secara

genetik misalnya kontrasepsi hormonal (Rauf, 2006).

Langkah untuk menurunkan kejadian dan kematian akibat dari kanker serviks dengan

melaksanakan berbagai pencegahan dan deteksi atau identifikasi. Dewasa ini telah dikenal

beberapa metode skrining dan deteksi dini kanker serviks, yaitu tets pap smear, IVA, pembesaran

IVA dengan gineskopi, koloskopi, servikografi, thin Prep dan tes HPV (Wilgin & Christin,

2011). Namun yang sesuai dengan kondisi di negara berkembang termasuk Indonesia adalah

menggunakan metode IVA karena tekniknya sederhana, biayanya murah, dan tingkat

sensitifitasnya tinggi. Oleh karena itu, tes IVA dianjurkan bagi semua perempuan berusia 30-50

tahun dan perempuan yang sudah melakukan hubungan seksual (Departemen Kesehatan

Republik Indonesia, 2007).

 BAB II

ANALISIS JURNAL

Kanker serviks adalah tumor ganas primer yang berasal dari sel epitel skuamosa. Pada

penyakit ini sebelum terjadinya kanker, akan di dahului oleh keadaa yang disebut lesi pra kanker

atau neoplasia intraepitel serviks (NIS). Sebagian besar perempuan yang mengidap kanker

serviks datang untuk memeriksakan keadaan nya pada stadium lanjut, karena pada stadium awal

tidak menimbulkan gejala. Kanker serviks disebabkan oleh Human Papilloma Virus (HPV)

onkogenik, yang menyerang pada leher rahim, infeksi HPV merupakan penyebab utama pada

penyakit ini.

Estimasi terbaru dari jumlah genotip HPV adalah 200 dengan 18 genotipe yang secara

langsung berhubungan dengan kanker serviks. Lima belas jenis HPV yang memiliki potensi

onkogenik yang kuat termasuk HPV 16, 18, 31, 33, 35,39, 45, 51, 52, 56, 58,59,68, 73, dan 82.

Jenis HPV ini dapat bersifat pra-insvasif dan infasif, HPV tipe 16 mendominasi infeksi (50-60%)

pada penderita kanker leher rahim disusul dengan tipe 18 (10-15%). HPV kanker serviks dengan

hasil yang negatif sangat jarang ditemui akan tetapi telah ditemukan, kemungkinan hal ini

disebabkan keterbatasan dengan metode deteksi atau mungkin karena hilangnya DNA HPV

selama perkembangan kanker.

Faktor resiko dapat terjadinya kanker serviks yaitu belum diketahui secara pasti sehingga

sangat sulit untuk dilakukannya deteksi dini, yang dapat di duga menjadi penyebab kanker

serviks antara lain aktivitas atau hubungan seksual pada usia dini kurang dari 18 tahun, pasangan

seksual dua orang atau lebih, cerai atau pisah dengan hubungan seksual yang tidak stabil,

melahirkan anak pada usia muda (kurang dari 18 tahun), hygiene perorangan yang rendah,

3
 4

kemiskinan, rangsangan terus menerus pada leher rahim misalnya frekuensi koitus yang tinggi,

peradangan, paritas yang tinggi (lebih dari 3), dan adanya bahan-bahan mutagen yang di duga

dapat merubah sel-sel pada jaringan rahim secara genetik misalnya sperma yang mengandung

bahan rokok, penggunaan kontrasepsi hormonal selama lebih dari lima tahun dan penyakit

infeksi menular (Klamidia, HIV, Herpes Simplek, Trikomonas Vaginalis).

Dari hasil penelitian yang dilakukan oleh Abdullah, Bawotong dan Hamel, 2013

menyatakan bahwa berdasarkan 42 responden dimana semuanya menggunakan kontrasepsi

hormonal dan non hormonal. Analisa berdasarkan umur paling banyak responden berada pada

usia 41-57 tahun dan paling sedikit pada kelompok umur 31-35 tahun. Berdasarkan tingkat

pendidikan paling banyak pada tingkat SMA dan paling sedikit pada S1, berdasarkan pekerjaan

pada kelompok IRT. Berdasarkan distribusi frekuensi distribusi analisis data pemakaian

kontrasepsi hormonal paling banyak responden yang terkena kanker serviks dimana responden

berada pemakaian pil dan paling sedikit pengguna suntik maupun implan. Sehingga dapat

disimpulkan bahwa terdapat hubungan yang signifikan antara pemakaian alat kontrasepsi

hormonal dengan kejadian kanker serviks dan kemungkinan terjadinya kanker serviks untuk ibu

dengan pemakaian kontrasepsi hormonal adalah 0,18 kali.

Tanda dan gejala yang dapat dilihat dari kanker serviks pada awal stadium invasif adalah

perdarahan di luar siklus haid, yang dimulai sedikit demi sedikit yang semakin lama semakin

banyak atau terjadi pendarahan diantara 2 masa haid, keputihan, nyeri pinggul dan gangguan

yang biasanya unilateral yang menjalar ke paha dan seluruh panggul atau bahkan tidak bisa

buang air kecil, nyeri di rasa ketika berhubungan seksual dan konstipasi.
 5

Pemeriksaan kanker serviks:

a. Pemeriksaan Fisik

Pemeriksaan serviks dilakukan untuk melihat perubahan portio vaginalis dan mengambil

bahan apus untuk pemeriksaan sitologi ataupun biopsi, pemeriksaan dilakukan lebih lanjut

pada palpasi bimanual vagina dan rektum untuk mengetahui massa pada rektum dan anus.

b. Test Pap Smear

Test papsmear konvensional terdapat dua jenis yaitu thin prep pap pada pemeriksaan ini

sample lendir diambil pada pemeriksaan dengan alat khusus (cerviks brush) bukan dengan

spatula kayu dan hasilnya tidak disapukan ke object-glas melainkan disemprot cairan khusus

untuk memisahkan kontaminan (darah dan lendir) sehingga hasil pemeriksaan lebih akurat.

Kedua ialaha Thin prep plus test HPV DNA, pada pemeriksaan ini sample di periksa apakah

mengandung DNA virus HPV.

c. Metode IVA

Untuk deteksi dini kanker serviks selain papsmear yaitu metode IVA (inspeksi visual asetat).

Persyaratan untuk dilakukan IVA test yaitu tidak sedang datang bulan atau haid dan 24 jam

sebelumnya tidak melakukan hubungan seksual.

Cara pemeriksaan teknik IVA menggunakan spekulum untuk melihat serviks yang telah

dipulas dengan asam asetat 3-5% . Hasil (+) pada lesi pankreas terlihat warna bercak putih

disebut : Aceti White Epitelium. Tindak lanjut IVA (+). Biopsi kategori pemeriksaan IVA

ada beberapa kategori yang digunakan, salah satunya ialah:

IVA negatif : Serviks normal

IVA radang : serviks dengan radang (servisitis) atau kelainan jinak lainya (polip

serviks)
 6

IVA positif : ditemukan bercak putih (aceto white ephitelium). Pada kelompok ini

merupakan sasaran untuk dilakukannya skrining kanker serviks dan merupakan untuk

temuan stadium kanker serviks.

d. Yodium atau Schillen test

Dalam klinis serviks yang terpapar oleh spekulum vagina, setelah menyeka lendir

permukaan, memoleskan larutan yodium, ke serviks dan forniks, bila ditemukan adanya

daerah yodium-negatif abnormal, bisa melakukan biopsi dan pemeriksaan patologis untuk

daerah ini.

e. Kolposkopi

Pemeriksaan dengan kolposkopi, merupakan pemeriksaan dengan pembesaran, melihat

kelainan epitel serviks, pembuluh darah setelah pemberian asam asetat. Pemeriksaan

kolposkopi tidak hanya terbatas pada serviks, tetapi pemeriksaan meliputi vulva dan vagina.

Pemeriksaan kolposkopi merupakan pemeriksaan standar bila ditemukan pap smear yang

abnormal.

f. Biopsi

g. USG

h. Penanda tumor

i. Radiologi

j. Endoskopi

k. Cystoscopy

l. Proktoskopi

m. Cek darah lengkap

n. MRI
 7

o. CT Scan

p. Bone Scan

q. BNO, IVP

Pencegahan Kanker Serviks dengan HPV Vaksinasi

Cara lain yang potensial untuk mencegah kanker serviks adalah menggunakan vaksinasi

HPV untuk mencegah infekasi HPV resiko tinggi yang selanjutnya menjadi kanker serviks. Jenis

vaksin yang disetujui oleh BPOM pada tahun 2006 yaitu Gardasil vaksin HPV quadrivalent

rekombinan. Jenis vaksin ini memiliki kemampuan mencegah inveksi HPV 16 dan 18 selain

HPV 6 dan 11, serta dapat digunakan pada perempuan 9-26 tahun. Vaksin ini memiliki

kemampuan untuk mencegah kanker serviks jika diberikan dalam jangka waktu tiga vaksinasi

yaitu dalam waktu 0 bulan, 1 sampai dengan 2 bulan dan 6 bulan. Gardasil memiliki kemampuan

untuk menyampaikan perlindungan terhadap vulva, kanker vagina dan neoplasma intra epitel.

Vaksin jenis ini memiliki perlindungan dengan massa 5 tahun pasca vaksinasi.

Pada tahun 2008 telah ditemukan vaksin ke dua yaitu cervarix HPV bivalen, cevarik di

indikasikan untuk digunakan pada wanita berusia 10 sampai dengan 25 tahun. Diberikan dalam

waktu tiga kali vaksinasi yaitu pada bulan 0, 1 sampai 2 dan bulan ke 6. Perlindungan pada jenis

vaksin ini terhadap HPV 16 dan 18 serta pra kanker yang terkait lesi untuk HPV 6 yaitu 4 tahun

pasca vaksinasi.

Skreening Kanker Serviks

Tujuan utama dilakukannya skrining kanker serviks adalah dengan menemukan tanda lesi

prekursor pada kanker dan awal asimtomatik invasif kanker serviks. Skreening dilakukan untuk

pemahaman vaksin HPV dan perannya dalam pencegahan kanker serviks. Skrining dilakukan

pada perempuan berusia 21 tahun, hal ini dikarenakan pada perempuan usia 21-29 tahun perlu
 8

mendapatkan papsmear konvensional atau cairan sitologi. Papsmear konvensional dapat

dilakukan setiap 2-3 tahun untuk perempuan lebih dari 30 tahundengan tiga kali negatif tes

sitologi. Skrining dihentikan pada perempuan yang berusia lebih dari 65 tahun dengan hasil

skrining sebelumnya negatif, dan tidak ada tes abnormal sebelumnya selama 10 tahun tahun

terakhir.

Pada tahap ini juga terdapat penatalaksanaan keperawatan promotif yaitu melakukannya

penyuluhan kesehatan masyarakat tentang kesehatan reproduksi wanita dan langkah-langkah

pencegahan kanker serviks hal ini bertujuan untuk meningkatkan kesadaran perempuan

pentingnya menjaga kesehatan reproduksi, serta pendidikan seksual yang baik dan benar

(penjelasan mengenai alat kontrasepsi dan perilaku seksual yang sehat).

 BAB III

PEMBAHASAN

Pada dasarnya melihat berdasarkan fenomena yang ada pada masyarakat, para wanita

kurang begitu peduli akan deteksi dini pada kanker serviks. Sehingga sangat diperlukan

skreening mengenai kanker serviks sedini mungkin yaitu pada usia remaja karena pada tahap ini

mereka mempersiapkan diri untuk menjadi wanita dewasa (McGraw, Ferrante, 2014). Akan

tetapi pada artikel yang di tulis oleh McGraw, Ferrante, 2014 tidak menyebutkan secara lengkap

langkah-langkah apa saja yang di lakukan pada tahap skrining tersebut, sehingga prosedur

skrining kurang jelas. Pada skrining ini dapat dilakukan konseling atau penyuluhan mengenai

pentingnya kebersihan sistem organ wanita dan hubungan seksual yang sehat untuk merubah

pola prilaku wanita pada hari-harinya, sehingga dapat mencegah peningkatan kejadian pada

penyakit kanker serviks. Selain skrining artikel tersebut menyarankan untuk pencegahan secara

dini dengan menggunakan HPV Vaksinasi, namun pada kenyataan yang ada vaksinasi tersebut

belum tersosialisasikan pada masyarakat dan belum terdapat dalam program pemerintah

sehingga membutuhkan biaya yang cukup besar untuk mendapatkan vaksinasi tersebut.

Pada jurnal yang di tulis oleh Abdullah, Bawotong dan Hamel, 2013. Terdapat hubungan

yang bermakna dengan pemakaian KB hormonal dengan kejadian kanker serviks dan dapat

beresiko 0,18 pada pengguna KB hormonal untuk terkena kanker serviks. Hal tersebut

merupakan salah satu faktor resiko terjadinya kanker serviks yaitu penggunaan KB hormonal

dalam jangka waktu lebih dari 5 tahun. Kekurangan pada penelitian ini tidak melihat jangka

waktu pemakaian alat kontrasepsi masa lampau dan apakah pemakaian digunakan secara terus

menerus atau diselang dengan menggunakan kontrasepsi non hormonal. Sehingga perlunya

9
 10

dilakukan skreening penggunaan alat kontrasepsi jenis dan jangka waktu pada wanita yang telah

menikah, dan memberikan pendidikan kesehatan mengenai alat kontrasepsi yang aman dengan

jangka waktu tertentu serta menyarankan pada wanita menikah lebih dari 30 tahun pentingnya

melakukan papsmear dan IVA test dalam jangka waktu 3 tahun atau 5 tahun sekali.
 BAB IV

SIMPULAN DAN SARAN

A. Simpulan

Kanker serviks merupakan penyebab paling umum pada penyakit kanker, perempuan di

dunia. Kanker serviks adalah tumor ganas primer yang berasal dari sel epitel skuamosa. Pada

penyakit ini sebelum terjadinya kanker, akan di dahului oleh keadaa yang disebut lesi pra kanker

atau neoplasia intraepitel serviks (NIS). Sebagian besar perempuan yang mengidap kanker

serviks datang untuk memeriksakan keadaan nya pada stadium lanjut, karena pada stadium awal

tidak menimbulkan gejala. Kanker serviks disebabkan oleh Human Papilloma Virus (HPV)

onkogenik, yang menyerang pada leher rahim, infeksi HPV merupakan penyebab utama pada

penyakit ini. yang dapat di duga menjadi penyebab kanker serviks antara lain aktivitas atau

hubungan seksual pada usia dini kurang dari 18 tahun, pasangan seksual dua orang atau lebih,

cerai atau pisah dengan hubungan seksual yang tidak stabil, melahirkan anak pada usia muda

(kurang dari 18 tahun), hygiene perorangan yang rendah, kemiskinan, rangsangan terus menerus

pada leher rahim misalnya frekuensi koitus yang tinggi, peradangan, paritas yang tinggi (lebih

dari 3), dan adanya bahan-bahan mutagen yang di duga dapat merubah sel-sel pada jaringan

rahim secara genetik misalnya sperma yang mengandung bahan rokok, penggunaan kontrasepsi

hormonal selama lebih dari lima tahun dan penyakit infeksi menular (Klamidia, HIV, Herpes

Simplek, Trikomonas Vaginalis). Test dasar yang digunakan untuk pemeriksaan gejala awal

pada kanker serviks yaitu dengan pemeriksaan fisik, papsmear dan IVA test. Pencegahan kanker

serviks dapat dilakukan dengan imunisasi atau vaksinasi HPV secara rutin berdasarkan masa

11
 12

perlindungannya dan skrining secara dini sangat diperlukan untuk menekan peningkatan

penyakit kanker serviks pada wanita.

B. Saran

Adapun yang perlu diperhatikan:

Sosialisasi mengenai pencegahan kanker serviks dengan vaksinasi HPV .

Selama melakukan skreening: perlu dilakukannya penjaringan pada wanita usia 21 tahun

terutama yang akan menjelang ke jenjang pernikahan, serta perlunya dilakukan pendidikan

kesehatan mengenai pentingnya kebersihan organ reproduksi wanita serta faktor resiko yang

dapat menimbulkan penyakit kanker serviks.

Diperlukan adanya SOP yang jelas untuk skreening serta tahapan selama skreening kanker

baik pada lingkungan masyarakat atau tenaga kesehatan.

Memberikan pendidikan kesehatan mengenai alat kontrasepsi yang aman dalam jangka

waktu yang diperlukan.

Menyarankan pasien dalam lingkungan pelayanan kesehatan masyarakat atau wanita yang

telah menikah di usia lebih dari 30 tahun untuk melakukan papsmear atau IVA test secara

rutin selama 3 atau 5 tahun sekali.

 DAFTAR PUSTAKA

Abdullah, Bawotong, Hamel. 2013. Hubungan Pemakaian Kontrasepsi Hormonal dan Non
Hormonal Dengan Kejadian Kanker Serviks di Ruang D Atas BLU, PROF, Dr, R. D.
Kandau Manado. www.download.portalgaruda.org. tanggal 01 September 2016.

McGraw, Ferrante. 2014. Update On Prevention And Screening Of Cervival Cancer.

www.ncbi.nim.nih.gov. Diunduh tanggal 01 September 2016.

Septadina, Kesuma, Handayani, dkk. 2014. Upaya Pencegahan Kanker Serviks Melalui
Peningkatan pengetahuan Kesehatan Reproduksi Wnita Dan Pemeriksaan Metode IVA
(Inspeksi Visual Asam Asetat) di Wilayah Kerja Peskesmas Kenten Palembang. www.
Journal.unsri.ac.id.Di unduh tanggal 01 September 2016.

Rauf, Syarul, 2006. Penanggulangan Kanker Leher Rahim. Makasar: WIDI

 LAMPIRAN JURNAL
World Journal of
Clinical Oncology
Submit a Manuscript: http://www.wjgnet.com/esps/
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx
DOI: 10.5306/wjco.v5.i4.744
WJCO 5th Anniversary Special Issues (3): Cervical cancer
Update on prevention and screening of cervical cancer
Shaniqua L McGraw, Rutgers-Robert Wood Johnson Medical
School, Department of Family Medicine and Community Health,
Somerset, New Jersey 08873, United States
Jeanne M Ferrante, Department of Family Medicine and Com-
munity Health, Rutgers-Robert Wood Johnson Medical School,
Cancer Institute of New Jersey, New Brunswick, New Jersey
08903, United States
Author contributions: McGraw SL performed the research,
drafted the article, and approved the final version to be published;
Ferrante JM conceived and designed the research, performed
research, critically revised the article, and approved the final ver-
sion to be published.
Correspondence to: Jeanne M Ferrante, MD, MPH, Depart-
ment of Family Medicine and Community Health, Rutgers-Rob-
ert Wood Johnson Medical School, Somerset, New Jersey 08873,
United States. jeanne.ferrante@rutgers.edu
Telephone: +1-732-7433222 Fax: +1-732-7433395
Received: December 28, 2013 Revised: April 11, 2014
Accepted: May 13, 2014
Published online: October 10, 2014
Abstract
Cervical cancer is the third most common cause of
cancer in women in the world. During the past few
decades tremendous strides have been made toward
decreasing the incidence and mortality of cervical can-
cer with the implementation of various prevention and
screening strategies. The causative agent linked to
cervical cancer development and its precursors is the
human papillomavirus (HPV). Prevention and screening
measures for cervical cancer are paramount because
the ability to identify and treat the illness at its pre-
mature stage often disrupts the process of neoplasia.
Cervical carcinogenesis can be the result of infections
from multiple high-risk HPV types that act synergisti-
cally. This imposes a level of complexity to identifying
and vaccinating against the actual causative agent.
Additionally, most HPV infections spontaneously clear.
Therefore, screening strategies should optimally weigh
the benefits and risks of screening to avoid the discov-
ery and needless treatment of transient HPV infections.
WJCO|www.wjgnet.com
World J Clin Oncol 2014 October 10; 5(4): 744-752
ISSN 2218-4333 (online)
2014 Baishideng Publishing Group Inc. All rights reserved.
TOPIC HIGHLIGHT
This article provides an update of the preventative
and screening methods for cervical cancer, mainly HPV
vaccination, screening with Pap smear cytology, and
HPV testing. It also provides a discussion of the new-
est United States 2012 guidelines for cervical cancer
screening, which changed the age to begin and end
screening and lengthened the screening intervals.
2014 Baishideng Publishing Group Inc. All rights reserved.
Key words: Cervical cancer; Cancer screening; Pap
smear; Human papillomavirus; Papillomavirus vaccines
Core tip: Screening is the best method to prevent cervi-
cal cancer. Screening strategies should weigh the bene-
fits and risks of screening to avoid discovery and need-
less treatment of transient human papillomavirus (HPV)
infections. Current United States guidelines recommend
Pap smear screening with conventional or liquid-based
method no frequent than every 3 years, or every 5
years in women greater than age of 30 if done in con-
junction with HPV testing. Screening is not recommend
in females younger than 21 years, regardless of age at
initiation of sex. In this population, options for preven-
tion include HPV vaccination and decreasing other risk
factors associated with HPV infection.
McGraw SL, Ferrante JM. Update on prevention and screen-
ing of cervical cancer. World J Clin Oncol 2014; 5(4): 744-752
Available from: URL: http://www.wjgnet.com/2218-4333/full/
v5/i4/744.htm DOI: http://dx.doi.org/10.5306/wjco.v5.i4.744
INTRODUCTION
The World Health Organization estimates that yearly,
about 530000 women worldwide are identified with cer-
vical cancer and 275000 women die from the disease[1].
Cervical cancer is heralded as being the third most com-
mon cause of cancer among women in the world and
744 October 10, 2014|Volume 5|Issue 4|

the second most common form of cancer in women in
the developing world[2]. Cervical cancer is responsible for
the largest cause of mortality in women due to cancer in
most developing countries.
There has been a large decline in the incidence and
death rate of cervical cancer in industrialized countries
observed during the past few decades. This unfortunately,
has not been mirrored by a similar decline in developing
nations. An example of this is illustrated by the 70% de-
crease in mortality caused by cervical cancer in the Unit-
ed States from 1955 to 1992. Each year this initial decline
in death caused by cervical cancer has been sustained at
a rate of a 3% decrease in the incidence of cervical can-
cer[2]. Similarly, in the United Kingdom there has been a
70% decline in the mortality caused by cervical cancer
recorded in 2008 than was reported 30 years prior [2]. In
industrialized nations the age-adjusted incidence of cervi-
cal cancer is 10 out of 100000 per year; however in devel-
oping nations the incidence of the disease can be as high
as 40 out of 100000. By 2030, it is expected that cervical
cancer will be responsible for the death of 474000 wom-
en annually with over 95% of these deaths anticipated to
occur in low- and middle-income countries (LMICs)[3].
HPV infection and cervical cancer
Infection with HPV is the main causative agent in cervical
cancer. The latest estimation of the number of genotypes
of HPV was 200 with 18 genotypes that are directly relat-
ed to cervical cancer[4,5]. The fifteen HPV types that have
a strong oncogenic potential include HPV 16, 18, 31, 33,
35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82. These high-
risk HPV typess account for 95% of all cervical cancer.
It has been found that greater than one HPV type
can exist in pre-invasive and invasive cervical cancer[6].
This imposes a level of complexity in identifying which
one is the actual causative agent, with various genotypes
depending on geographical regions. While high-risk HPV
16 and 18 are accountable for around 90% of all cervical
cancer[7], there is greater than average presence of sub-
types 31 and 45 detected in the developing world[8]. There
is also a prominent presence of HPV 58 associated with
pre-invasive lesions in women in various countries, in-
cluding Thailand, Uganda, Zambia and Cameroon [9-12].
The most carcinogenic HPV genotype is HPV 16,
which mostly causes squamous cell carcinoma. HPV 18
mostly causes adenocarcinoma, a cancer that is less fre-
quently found but more aggressive, resulting from the
endocervical glandular[13]. However, cervical carcinogen-
esis may arise from infections with many high-risk types
that act synergistically[14]. The Bethesda classification en-
compasses the biological behavior of cervical squamous
intraepithelial lesions (SILS)[8]. The classification system
partitions abnormal squamous epithelial cells into four
categories: (1) atypical squamous cells of undermined sig-
nificance (ASCUS); (2) low grade squamous intraepithelial
lesions (LSILS), including light dysplasia/cervical intraepi-
thelial neoplasia (CIN) 1 in addition to HPV associated
cell changes; (3) high-grade squamous intraepithelial le-
WJCO|www.wjgnet.com
McGraw SL et al . Prevention and screening of cervical cancer
sions (HSIL), encompassing moderate dysplasia/CIN
2, severe dysplasia, and carcinoma in situ/CIN 3; and (4)
squamous cell carcinoma[8]. Almost 90% of infections
with HPV clear on its own within 1-2 years[15]. High-grade
cervical intraepithelial lesions that are classified as CIN
2 have a 40% chance of regression. High-grade cervical
intraepithelial lesions that do not regress are categorized
as CIN 3. These lesions have a 30% probability of pro-
gression to invasive cervical cancer[16]. HPV 16 is the most
persistent infection and the type that is most likely to
progress to CIN 3, carcinoma in situ, and invasive cervical
cancer. HPV negative cervical cancer is extremely rare,
but it has been found. This form of cervical cancer is be-
lieved to be due to an artifact caused by limitations in the
current detection methods or perhaps due to the loss of
HPV DNA during the progression to cancer.
Risk factors for cervical cancer
Sexually transmitted infection with HPV is the strongest
risk factor for development of cervical cancer. There are
multiple risk factors that have been connected with the
acquisition of HPV infection and cervical cancer (Table
1). HPV acquisition is most dependent on genital con-
tact. This prominent risk increases with higher number
of sexual partners of a woman or her partner [17-19]. Other
sexual and reproductive risk factors associated with
HPV infection and cervical cancer include: initiation of
sexual activity at an early age ( 18 years), earlier age at
first full-term pregnancy (< 18 years), high parity (4 or
greater vaginal deliveries), use of combined hormonal
oral contraceptives for longer than 5 years, and a history
of other sexually transmitted infections [e.g., chlamydia,
human immunodeficiency virus (HIV), herpes simplex
2][18,19]. The use of tobacco, both current and past, in-
creases the risk of squamous cell cervical carcinoma,
and the risk rises with quantity of cigarettes smoked per
day and number of years smoked[19]. Infection with HIV
is strongly associated with incidence and persistence of
HPV infection, and advancement to invasive cervical
cancer from squamous intraepithelial lesions [19]. In fact,
cervical cancer is one of the acquired immunodeficiency
syndrome (AIDS)-defining illness, i.e., a person with HIV
who develops cervical cancer is considered to have AIDS.
The acquisition of HPV is most dependent on contact
with the genital skin and condom use is associated with
reduced cervical cancer risk[19]. However, condom use is
only 70% effective in averting the transmission of HPV
since there is remaining contact with genital skin that is
not covered by the surface of the condom[17]. In sum-
mary, counseling for tobacco cessation, delaying initiation
of sexual intercourse, using condoms, and decreasing
number of sexual partners may prevent HPV infection
and help to reduce the risk of cervical cancer.
CERVICAL CANCER PREVENTION WITH
HPV VACCINATION
Another potential way to prevent cervical cancer is the
745 October 10, 2014|Volume 5|Issue 4|
 McGraw SL et al . Prevention and screening of cervical cancer
Table 1 Cervical cancer risk factors
Cervical cancer risk factors [17-19]
Genital Infection with high risk human papillomavirus
HIV infection
Smoking
Younger age at first sexual intercourse
Greater number of sexual partners
Oral contraceptives use greater than 5 yr
Having 4 or greater full-term pregnancies
History of sexual transmitted diseases
HIV: Human immunodeficiency virus.
use of HPV vaccination to prevent high risk HPV infec-
tion and subsequent cervical carcinogenesis. The Food
and Drug Administration (FDA) approved in 2006, Gar-
dasil, a recombinant quadrivalent HPV vaccine. This vac-
cine has the capability of preventing infection with HPV
16 and 18 in addition to HPV 6 and 11, and it is targeted
for use in females 9-26 years of age[20]. It has been mar-
keted as having the ability to prevent genital warts as well
as cervical cancer when given in three vaccinations, at
months 0, 1 to 2, and 6[21]. Gardasil also has the capabil-
ity to convey protection against vulvar, vaginal cancer
and intraepithelial neoplasia, and recently, for the deter-
rence of genital warts in males age 9-26 years[6]. Short to
medium clinical studies show the capability of Gardasil
to protective against HPV-16 and 18 infections and its as-
sociated precancerous lesions for up to 5 years post vac-
cination[6,8,13].
In 2008, a second vaccine, Cervarix, the HPV bivalent
vaccine targeting HPV 16 and 18 was approved[22]. Cer-
varix is indicated for use in females aged 10 to 25 years
when given in three vaccinations at months 0, 1 to 2, and
6[23]. Cervarix is effective against anogenital warts caused
by HPV, precancerous lesions, and cervical cancer[6].
Short to medium clinical studies show Cervarix conveys
protection against HPV-16/18 and its associated precan-
cerous lesions for 6.4 years post vaccination[2,10,15,20] .
The two HPV vaccines, Gardasil and Cervarix, are
currently approved in over 100 countries. In their indi-
vidual trials, the efficacy of Cervarix in protecting against
cervical cytologic abnormalities in HPV-nave women is
slightly higher than Gardasil[19]. Cervarix also seems to
have higher cross-protection against other nonvaccine
HPV types, as evidenced by its higher reduction in exci-
sional treatments for CIN 2/3 disease compared to Gar-
dasil, and its efficacy in decreasing incidence of genital
warts caused by HPV 6, 11, and 74[19]. However, clinically
significant differences in efficacy of Gardasil vs Cervarix
is difficult to discern and will not be apparent for many
years. Researchers believe that the differences will be re-
vealed with longer-term evaluations of women that were
vaccinated in countries with population-based registries
that can track HPV associated cervical lesions[8].
There are a cluster of symptoms that have been re-
ported most frequently in correlation to administration
WJCO|www.wjgnet.com
of the HPV vaccines including pain where injected (78%),
ecchymosis (17%), fainting (15%), and swelling (14%).
These side effects have been reported most commonly in
younger than older girls[24].
Routine HPV vaccination of girls is recommended
by the Centers for Disease Control and Preventions Ad-
visory Committee on Immunization Practices (ACIP) at
11 to 12 years of age with catch-up vaccinations at 13 to
26 years of age[25] (Table 2). However, the American Can-
cer Society has not found enough research evidence to
recommend for or against routine vaccination of females
age 19 to 26 years[24]. Young women are the targeted
group because immunological response is greatest in girls
aged 10-15 years, and the vaccine has greatest efficacy in
girls who havent initiated sex[26]. Estimations have been
made that only 7% of students in United States high
schools report having started sexual intercourse prior
to 13 years of age[26]. In the developing world there is a
much variation in the prevalence of virginity and the age
which women marry. Therefore, international vaccination
programs may have to change according to their country
s conditions and traditions[27].
Barriers to implementation of HPV vaccine
The acquisition of immunity of the entire population or
herd immunity has been met by a great deal of challeng-
es. Advocates for the vaccine estimate that approximately
70%-80% of girls that are pre-pubertal are required to be
vaccinated to obtain heard immunity. This level of im-
munity will be hard to reach in light of the fact that many
conservatives in the US have described the drug as the
promiscuity vaccine and have imposed their fears that
inoculating preteen girls will disrupt their message of ab-
stinence from pre-marital sexual intercourse via what they
have called the disinhibition effects[28]. All of this po-
litical rhetoric has resulted in a shift in public opinion of
the vaccine and resulted in a decline in the percentages of
parents that are in favor of the vaccine. Interestingly, the
intention to vaccinate with HPV is greatest when the vac-
cine is depicted that it is free or cheaply available and that
it prevents cancer, rather than preventing an infection
that is sexually transmitted[25]. Studies show that there are
still realist barriers in place as it pertains to the cost of
the vaccine as well as the stigma that is attached to it[27].
Advocates for the HPV vaccination also believe that
herd immunity will only authentically be obtained when
there is the existence of a gender-inclusive vaccination
policy[28]. There is a belief that men play a pivotal role
as carriers of HPV. However, there has been a limited
amount of clinical trials that have been carried out on
boys as it pertains to HPV vaccinations. This fact is even
reflected in the lack of attention given to administering
HPV vaccines to boys and men in United States newspa-
pers[29]. Positive strides have been made with regards to
boys and men immunization when the ACIP approved
the non-routine vaccination of Gardasil in boys age nine
to 18 years for the purpose of preventing genital warts[29].
While it is known that males represent a reservoir for fe-
746 October 10, 2014|Volume 5|Issue 4|
 McGraw SL et al . Prevention and screening of cervical cancer

Table 2 Recommendations for human papillomavirus vaccination by the Advisory Committee on Immunization Practices

Population Recommendation for HPV vaccination

Females 11-12 yr ofRoutine

age vaccination with 3 doses at 0, 1-2, and 6 mo of either HPV2 or HPV4. Can be initiated as early as age 9 and be
given up to age 26
Females 13-26 yr of ageCatch up immunization with 3 doses at 0, 1-2, and 6 mo of either HPV2 or HPV4
Males age 11-12 yrRoutine vaccination with HPV4 with 3 doses at 0, 1-2, and 6 mo. Can be initiated as young as age 9 and be given up to
age 26
Female or males withMinimum time between 1st and 2nd vaccine doses is 1 mo. Minimum time between the 2 nd and 3rd vaccine doses is 3 mo.
inadequate dose of HPV vaccine Insufficient receipt of HPV vaccine due to shorter than the recommended dosing interval should be re-administered
Females or males withHPV vaccination does not need to be restarted. The 2 nd dose should be administered as quick as possible if delayed
interrupted vaccine scheduleafter the 1st dose. The 2nd and 3rd dose should be separated by 3 mo. If just the 3 rd dose is late, it should be given as soon
as possible

HPV: Human papillomavirus vaccine; HPV2: Bivalent human papillomavirus vaccine (Cervarix); HPV4: Quadrivalent human papillomavirus vaccine (Gar-
dasil).

male HPV infections, HPV vaccination in boys is contro-
versial because there is no proof that it is cost-effective[29].
While the controversy over the cost-effectiveness of the
vaccine in males as well as the debate surrounding the use
of the vaccine in young girls continue, some question the
true effectiveness of the HPV vaccine. The Females United
to Unilaterally Reduce Endo/Ectocervical Disease (FU-
TURE) trials that validated the effectiveness of the vaccine
were only conducted over a three-year timeline[21]. However,
the average time from carcinogenic HPV infection to inva-
sive cervical cancer, if it happens, is at least 25-30 years[22,30].
Furthermore, it takes approximately five to seven years
from acquisition of HPV infection and the first incidence
of a pre-invasive cervical lesion[22]. As a result of this rea-
soning, some argue that to declare that the vaccine averted
the occurrence of cervical lesions after only a few years of
follow-up has the potential to be misleading.
Another factor that concerns the international com-
munity is the presence of serotypes that are not targeted
by the two HPV vaccines[31,32]. For example, the quadriva-
lent vaccine prevents infection from HPV 16, 18, 6 and
11, and the bivalent vaccine targets HPV 16 and 18, how-
ever, there are other genotypes of HPV that are prevalent
in other geographical regions. Consequently, a daunting
question is imposed on the effectiveness of the current
vaccines in these other regions.
CERVICAL CANCER SCREENING
The ultimate objective of cervical cancer screening is to
find high-grade cancer precursor lesions and early as-
ymptomatic invasive cervical cancer, while avoiding the
discovery and needless treatment of fleeting HPV infec-
tion and its resultant benign lesions. Since the majority
of HPV infections and many CIN 1 and CIN 2 cases
are transient, there is a large margin for harm that is as-
sociated with discovering these fleeting lesions, including
mental stress, physical discomfort incurred from extra
diagnostic and treatment measures (e.g., vaginal pain,
bleeding, infection), and a higher risk of maternity com-
plications such as preterm delivery after treatment[33,34].
The systemic screening with the Papanicolaou cy-
tological test (Pap smear) to find pre-invasive cervical
lesions and early stage cancer has drastically reduced the
incidence and death from cervical cancer in the United
States and other industrialized nations [34]. However,
cervical cancer still produces much morbidity and mor-
tality in certain sub-populations. In the United States,
approximately one-half of cervical cancer is diagnosed
in women who were never screened. Groups of the
population that participate least frequently in Pap smear
include: women who are less educated, older, uninsured,
or homeless; migrant workers who face language barriers;
and lesbians[24]. The segment of the United States popu-
lation at highest risk for cervical cancer is Hispanic and
African American women. Fortunately, these populations
have benefited from community-based awareness raising
programs, which have successfully resulted in a decline in
their prevalence of cervical cancer[35]. It is then practical
to reason that programs similar to the ones implemented
on Hispanic and African-American women should be ap-
plied to the various groups of the population where the
women are at greater risk to having cervical cancer due to
their lack of compliance with Pap smear screening.
Cervical cytology tests
There are two forms of Pap smears, conventional and
liquid-based cytology. In the conventional method cells
are obtained from the neck of the cervix and then the
cells are spread on a glass slide. In the liquid-based cytol-
ogy method, the cells are obtained from the neck of the
cervix, but instead of being spread on a glass slide, they
are placed in a small glass vial that contains preserving
fluid. There has been much debate with regards to which
form is superior. Current evidence indicates that no clini-
cally important differences in sensitivity or specificity ex-
ists when comparing liquid-based and conventional cytol-
ogy[36]. The United States Preventive Services Task Force
(USPSTF) considers both of these methods to be of
substantial net benefit when they are administered in the
appropriate age groups at the recommended interval[37].
HPV testing
Although the Pap test has proven to be a greatly effec-

WJCO|www.wjgnet.com 747 October 10, 2014|Volume 5|Issue 4|

 McGraw SL et al . Prevention and screening of cervical cancer
tive tool for screening in countries that have the capacity
to implement it to the majority of its population, one
problem with the test is its high rate of false positive
cytology[38]. The higher understanding of the correlation
between HPV and cervical cancer led to the develop-
ment of molecular tests for HPV with greater sensitivity
(approximately 90 percent)[39]. However, it has slightly
reduced specificity for CIN2 and CIN3 when compared
with cytology. The currently available DNA test detects
only the high-risk HPV types, and has greater reproduc-
ibility than cytology. The HPV test is a solution hybrid-
ization that has the capacity to amplify the DNA signal
in the assays of the 13 HPV high-risk types[14]. The HPV
test should be performed only in women age 30 years
or more because women less than 30 years have a high
prevalence of transient infection and a low prevalence of
underlying high-grade lesions[37]. Therefore, HPV DNA
testing in women under the age of 30 can lead to un-
needed evaluation and overtreatment[37].
At the present time HPV DNA testing has the high-
est sensitivity, which can additionally be used with Pap
smears (co-testing) for optimizing diagnosis of high-
grade cervical intraepithelial neoplasia[39]. In women with
mild or borderline abnormal Pap results, a Pap-plus-HPV
test may be better, since a negative HPV DNA test has
the potential to assure women that their Pap smear result
is probably untrue; whereas treatment for a positive HPV
DNA test may begin quicker in these women due to the
high sensitivity of this test[40].
Visual inspection with acetic acid
Low-and-middle-income countries (LMICs) are faced
with a lack of critical resources for health in general
and often an even larger deficit for preventative health
initiatives for women. To combat this, LMICs pursue
screening options that work within the various societal
confounds faced by women in their countries. The ma-
jority of these LMICs do not have the current capacity
to sustain cytology-based cervical cancer prevention
programs[41]. In these societies, the Pap test is hindered
by numerous operational factors that inhibit quality, in-
cluding the follow-up challenges of multiple visits for
screening and later post-diagnosis therapy, inefficient
recall and referral systems, inadequate resources for
screening and treatment, and competing priorities in the
healthcare systems[41]. A viable alternative to the Pap test
has been developed due its low cost and ability to see-
and-treat in one visit. This screening method, known as
visual inspection with acetic acid (VIA), partnered with
cryotherapy-based treatment of VIA-positive lesions is
a testing method that has been readily mastered by non-
physician providers and has been extensively studied as
a viable alternative to the Pap smear[41,42]. A method of
screening that is gaining increasing popularity in LMICs
is the combination of VIA-based see-and-treat plat-
forms with HPV DNA testing, given that they have the
benefit of same-visit benefit of triage by VIA-based
screening[43-45]. This opportunity is made possible with the
WJCO|www.wjgnet.com
ongoing development of low-cost, rapid molecular-assay
technologies for HPV that may function optimally in the
field[46,47] .
CURRENT GUIDELINES FOR CERVICAL
CANCER SCREENING
In the United States, there has recently been a shift in the
way that screening for cervical cancer is being conducted
with recognition that yearly screening was unnecessary
and caused higher rate of harms. This is due to greater
understanding of the pathological development of cervi-
cal cancer and the discovery of the HPV DNA test and
HPV vaccines that have occurred in the last decade. Con-
sequently, screening guidelines have evolved rapidly, and
many of the organizations that develop screening guide-
lines now agree on the screening recommendations[27,48,49].
The American Cancer Society (ACS), American Society
for Colposcopy and Cervical Pathology (ASCCP), and
the American Society of Clinical Pathology (ASCP) all
tasked expert panels within the past five years to review
the available evidence on cervical cancer screening and
jointly produce a new cervical cancer screening guideline.
At the same time, the United States Preventive Services
Task Force (USPSTF) developed an updated systematic
review of cervical cancer screening. On March 14, 2012,
The ACS/ASCCP/ASCP group[33] and the UPSTF[36] re-
leased their updated guidelines. The American Congress
of Obstetrics and Gynecologist (ACOG) issued their
updated guidelines for cervical cancer screening shortly
thereafter in November 2012[50]. The consensus of rec-
ommendations made by these organizations, as it pertains
to cervical cancer screening, are for the general popula-
tion only. The guidelines are not for women that are at
a high risk, as they may need more frequent screenings,
including women with a history of cervical cancer, who
are immunocompromised, or were exposed in utero to
diethylstilbestrol[50].
Table 3 presents the current guidelines for specific
age groups. These differ from previous recommenda-
tions most notably in when to begin screening and the
screening intervals. Women before the age of 21 years
should not have Pap smears, irrespective of the age when
they initiated sexual activity[37,48,49]. The previous guide-
lines by the ACS in 2002 and 2003 stated that Pap smears
should start 3 years following the initiation of sexual
intercourse[37,51]. There has been a call for lengthening the
screening intervals in two of the age classifications. The
updated ACS/ASCCP/ASCP and ACOG guidelines[51,52]
have increased the time between Pap smears to 3 years in
females between ages 21 to 29. Their previous guidelines
recommended screening be done every 2 years. The rea-
son behind this change in the guidelines is because 2-3
year screening of women before age 30 carry similar pre-
dicted lifetime risk of cervical cancer mortality (0.05 per
1000 women); however screening women every 2 years
increases the risk of colposcopies by 40% compared with
screening every 3 years[49]. Hence, 3 year screening in
748 October 10, 2014|Volume 5|Issue 4|
 McGraw SL et al . Prevention and screening of cervical cancer

Table 3 Comparison of cervical cancer screening guidelines

Population Current Guidelines Prior ACS guideline 2002/2003 Prior ACOG Prior USPSTF guideline 2003
ACS/ACOG/USPSTF 2012 guideline 2009

Females younger than Begin screening

Begin 3atyrage
following
21 the onset ofBegin 3 yr following Begin within 3 yr of onset
21 yr of age vaginal intercourse, but no later than 21 the onset of vaginal of sexual activity or age 21,
yrintercourse, but no whichever is earliest
later than 21 yr
Females age 2129 yr Conventional Pap or liquidConventional Pap: Annually; everyCytology every 2 yr
30 with 3 negativebased cytology alone every 3 2-3 yr for females
yrcytology tests Conventional Pap: At least every
Liquid-based cytology: Every 2 yr; 3 yr
every 2-3 yr for females 30 yr with 3 Liquid-based cytology:
negative cytology tests Insufficient evidence
If HPV testing used: If HPV testing used: Insufficient
Every 3 yr if HPV negative and evidence
cytology negative
Females age 3065 yr HPV and Pap smear co-testingHPV and cytology co-
every 5 yr or Pap smear alonetesting every 3 yr
every 3 yr. Do not use HPV
testing alone.
Women older than 65 Stop screening if adequateStop screening in Women 70 yr with Stop between 65 and
prior negative screening result 3 or more recent, consecutive negative 70 yr of age after > 3
and women not at high risktests and no abnormal tests in previous consecutive negative
10 yrcytology tests over
the past 10 yr
Women afterNo screening if removal ofDiscontinue if hysterectomy for benign Stop screening
hysterectomycervix and no prior high grade reasons and no previous high-grade
pre-cancer or cervical cancer CIN No screening if adequate prior
Women who wereSame as non-immunizedNo vaccines recommended for use atSame as non- negative screening result and
immunized with HPV womenthis time periodimmunized women women not at high risk

Discontinue if hysterectomy
done for benign reasons

No vaccines recommended for

use at this time period

ACS: American Cancer Society; ACOG: American Congress of Obstetricians and Gyenocologists; USPSTF: United States Preventive Services Task Force;
HPV: Human papillomavirus; CIN: cervical intraepithelial neoplasia.

women younger than age 30 years has the optimal benefit
to risk ratio. In women 30 to 65 years of age, screening
can be done every 5 years if the womans result on co-
testing with Pap smear and HPV testing are negative,
since co-testing increases the sensitivity of screening, and
co-testing every 5 years results in fewer colposcopies and
comparable cancer risk than Pap smear screening every 3
years[52,53]. Cytology testing only at 3-year intervals is also
satisfactory in this patient population. The new guidelines
also recommend a decrease in the age that screening is
stopped, from 70 to 65 years[49,50,54]. The reason for this
is that studies show in women age 65 or older, new high-
risk HPV infection is associated with a extremely low
absolute risk of HPV persistence and progression to
CIN3[55,56].
There are some special circumstances that require
specific recommendations in the screening guidelines.
The new guidelines maintain previous recommendations
to not screen women that have received hysterectomies
with excision of the cervix for a benign cause and who
do not have prior history of cervical cytology higher than
CIN2[37,48,49]. This recommendation has been made in part
based on evidence produced by a large study of 5330
screening Pap smears in women with previous hysterec-
tomy where there was just one person found with dys-
plasia and none with cervical cancer[56]. Another unique
circumstance that has arisen since 2006 was the advent
of the HPV vaccine. Current guidelines recommend the
same screening strategy in individuals that have received
the vaccine as in individuals that have not had the vaccine
because it will be another decade or more before model-
ing studies predicting the effectiveness of the vaccine will
be available[57]. The guidelines also address the situation
when women have a negative Pap smear but a positive
HPV test. The ACS/ASCCP/ASCP and ACOG recom-
mend genotyping of HPV 16/18 and if positive, imme-
diate colposcopy[49]. However, evidence for HPV 16/18
genotyping is sparse; therefore, an acceptable alternative
option is to perform the combined HPV and cytology
testing again within 12 mo[49,58]. These recommendations
are based on results found in large cohort studies show-
ing that the risk of CIN 3 approximates 10% over 1 to
4 years when a womans test is evident for HPV 16, and
over 2 to 5 years if the womans test shows HPV 18[59,60].
DISCUSSION AND FUTURE PERSPECTIVE
ON CERVICAL CANCER PREVENTION
AND SCREENING
With the advent of the HPV vaccine and the limitless
screening possibilities that have been afforded by the
growing understanding of HPV and the role that it plays
in the evolution of cervical cancer, there is a real possibil-

WJCO|www.wjgnet.com 749 October 10, 2014|Volume 5|Issue 4|

 McGraw SL et al . Prevention and screening of cervical cancer
ity that cervical cancer can be eliminated in the future.
However, for that vision to become a reality there are
numerous complexities that have to be resolved with
regards to prevention as well as to screening for cervical
cancer. The innovative strides that have made been made
at the present time must be met by global efforts that are
tailored to various societal confines.
In the United States there has been a push by heath
care providers for immunization with HPV vaccine rou-
tinely in young women. This effort has not only been met
by opposition created from those challenging the moral-
ity and questioning the effectiveness of the vaccine; it has
also been met by exclusion of male counterparts in the
dissemination of this vaccine, as well as the ever present
lack of access of certain populations to adequate health
care. Individuals that are at higher risk of acquiring cer-
vical cancer are those that demonstrate less knowledge
of HPV and the HPV vaccine. Therefore, educational
outreach and program funding is needed that are targeted
at reaching the subgroups of the population with low
health care literacy and who are at risk of succumbing to
the morbidity and mortality of this preventable cancer.
The call to local and governmental officials to en-
hance the educational outreach and program funding
as a means to decrease the incidence of morbidity and
deaths due to cervical cancer is also at the frontline of
the dialogue in LMICs. Immunization of women with
HPV vaccine to potentially prevent cervical cancer in
these regions may take a back seat to other health care
issues in light of the cost and the unique blend of geno-
types that are present based on the geographical region.
Fortunately, officials in these regions are becoming more
knowledgeable of the advantages of implementing in-
novative cervical cancer see-and-treat programs. There
is a continued need for industrialized nations to lend aid
to these counties. This aid should not only be sent in the
form of the monetary contributions that have been made
by vaccine manufactures; they should continue sending
aid via providing the service of individuals that can train
their non-physician workforce who do a great deal to
treat the masses of women in their countries.
In both LMICs and developed countries, the advent
of HPV DNA testing has had a tremendous impact on
the way that screening for cervical cancer is conducted.
Affordable versions of this test are being developed, non-
physician providers can perform it independently, and
the results can be obtained the same day. More research
needs to be done to see if testing with this technology
should be conducted as the primary testing method,
especially in hard to reach populations, since compared
to cytology, it offers extended safety after a negative re-
sult. Some experts argue that because testing for HPV
has greater sensitivity than Pap smear, while Pap smear
screening has greater specificity, HPV testing should be
performed initially and then obtain Pap smear screen-
ing for patients testing positive for HPV. The potential
advantage to this was seen in a Canadian trial that found
that HPV testing followed by Pap smear caused lower re-
WJCO|www.wjgnet.com
ferrals for colposcopy than did either alone (1.1% vs 2.9%
with only Pap smear or 6.1% with just HPV testing)[59].
The greatest effect on mortality rates from cervi-
cal cancer is on women that are unscreened or under
screened. There is a huge need to continue with the in-
novative strides that have been made to overcome the
health care barriers crippling this population. If this
population is able to benefit from low-cost screening and
vaccinations subsidized by the government and contin-
ued efforts that are being made possible by the growing
dialogue surrounding cervical cancer, it is possible that
women in future generations will no longer succumb to
cancer of the cervix.
REFERENCES
1 Appleby P, Beral V, Berrington de Gonzlez A, Colin D,
Franceschi S, Goodhill A, Green J, Peto J, Plummer M, Sweet-
land S. Cervical cancer and hormonal contraceptives: collab-
orative reanalysis of individual data for 16,573 women with
cervical cancer and 35,509 women without cervical cancer
from 24 epidemiological studies. Lancet 2007; 370: 1609-1621
[PMID: 17993361 DOI: 10.1016/S0140-6736(07)61684-5]
Arbyn M, Castellsagu X, de Sanjos S, Bruni L, Saraiya M,
2
Bray F, Ferlay J. Worldwide burden of cervical cancer in
2008. Ann Oncol 2011; 22: 2675-2686 [PMID: 21471563 DOI:
10.1093/annonc/mdr015]
Saxena U, Sauvaget C, Sankaranarayanan R. Evidence-
based screening, early diagnosis and treatment strategy of
cervical cancer for national policy in low- resource countries:
3 example of India. Asian Pac J Cancer Prev 2012; 13: 1699-1703
[PMID: 22799391 DOI: 10.7314/APJCP.2012.13.4.1699]
Garland SM. Can cervical cancer be eradicated by prophy-
lactic HPV vaccination? Challenges to vaccine implementa-
tion. Indian J Med Res 2009; 130: 311-321 [PMID: 19901440]
Woodman CB, Collins SI, Young LS. The natural history of
4 cervical HPV infection: unresolved issues. Nat Rev Cancer
2007; 7: 11-22 [PMID: 17186016 DOI: 10.1038/nrc2050]
Choi YH, Chapman R, Gay N, Jit M. Potential overestima-
tion of HPV vaccine impact due to unmasking of non-vac-
5
cine types: quantification using a multi-type mathematical
model. Vaccine 2012; 30: 3383-3388 [PMID: 22480925 DOI:
10.1016/j.vaccine.2012.03.065]
6 Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kum-
mer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muoz N.
Human papillomavirus is a necessary cause of invasive
cervical cancer worldwide. J Pathol 1999; 189: 12-19 [PMID:
10451482 DOI: 10.1002/(SICI)1096-9896(199909)189: 1<12: :
AID-PATH431>3.0.CO; 2-F]
Clifford GM, Rana RK, Franceschi S, Smith JS, Gough G,
7
Pimenta JM. Human papillomavirus genotype distribu-
tion in low-grade cervical lesions: comparison by geo-
graphic region and with cervical cancer. Cancer Epidemiol
Biomarkers Prev 2005; 14: 1157-1164 [PMID: 15894666 DOI:
10.1158/1055-9965.EPI-04-0812]
Sukasem C, Pairoj W, Saekang N, Pombubpha H, Srichun-
rasami C, Pongtippan A, Junyangdikul P, Chantratita W.
8 Molecular epidemiology of human papillomavirus geno-
type in women with high-grade squamous intraepithelial
lesion and cervical cancer: will a quadrivalent vaccine be
necessary in Thailand? J Med Virol 2011; 83: 119-126 [DOI:
10.1002/jmv.21948]
Odida M, de Sanjos S, Quint W, Bosch XF, Klaustermeier J,
Weiderpass E. Human Papillomavirus type distribution in
9 invasive cervical cancer in Uganda. BMC Infect Dis 2008; 8:
85 [PMID: 18577214 DOI: 10.1186/1471-2334-8-85]
10
750 October 10, 2014|Volume 5|Issue 4|

11 Sahasrabuddhe VV, Mwanahamuntu MH, Vermund SH,
Huh WK, Lyon MD, Stringer JS, Parham GP. Prevalence and
distribution of HPV genotypes among HIV-infected women
in Zambia. Br J Cancer 2007; 96: 1480-1483 [PMID: 17437020]
Desruisseau AJ, Schmidt-Grimminger D, Welty E. Epi-
12 demiology of HPV in HIV-positive and HIV-negative
fertile women in Cameroon, West Africa. Infect Dis Ob-
stet Gynecol 2009; 2009: 810596 [PMID: 20169094 DOI:
10.1155/2009/810596]
Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de
Sanjose S, Bruni L, Tortolero-Luna G, Kjaer SK, Muoz N.
13 Epidemiology and natural history of human papillomavirus
infections and type-specific implications in cervical neopla-
sia. Vaccine 2008; 26 Suppl 10: K1-16 [PMID: 18847553 DOI:
10.1016/j.vaccine.2008.05.064]
Trottier H, Mahmud S, Costa MC, Sobrinho JP, Duarte-
Franco E, Rohan TE, Ferenczy A, Villa LL, Franco EL. Hu-
man papillomavirus infections with multiple types and risk
of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2006;
14 15: 1274-1280 [PMID: 16835323 DOI: 10.1158/1055-9965.
EPI-06-0129]
Rodrguez AC, Schiffman M, Herrero R, Wacholder S,
Hildesheim A, Castle PE, Solomon D, Burk R. Rapid clear-
ance of human papillomavirus and implications for clinical
focus on persistent infections. J Natl Cancer Inst 2008; 100:
513-517 [PMID: 18364507 DOI: 10.1093/jnci/djn044]
15 Naucler P, Ryd W, Trnberg S, Strand A, Wadell G, Elfgren
K, Rdberg T, Strander B, Johansson B, Forslund O, Hans-
son BG, Rylander E, Dillner J. Human papillomavirus and
Papanicolaou tests to screen for cervical cancer. N Engl J
Med 2007; 357: 1589-1597 [PMID: 17942872 DOI: 10.1056/
NEJMoa073204]
16 Winer RL, Hughes JP, Feng Q, OReilly S, Kiviat NB, Hol-
mes KK, Koutsky LA. Condom use and the risk of genital
human papillomavirus infection in young women. N Engl
J Med 2006; 354: 2645-2654 [PMID: 16790697 DOI: 10.1056/
NEJMoa053284]
Wen LM, Estcourt CS, Simpson JM, Mindel A. Risk factors
for the acquisition of genital warts: are condoms protective?
Sex Transm Infect 1999; 75: 312-316 [PMID: 10616354 DOI:
17 10.1136/sti.75.5.312]
Harper DM, Demars LR. Primary Strategies for HPV
Infection and Cervical Cancer Prevention. Clin Obstet-
Gynecol 2014; 57:256-278 [PMID: 24686336 DOI: 10.1097/
GRF.0000000000000027]
FUTURE II Study Group. Quadrivalent vaccine against hu-
18 man papillomavirus to prevent high-grade cervical lesions.
N Engl J Med 2007; 356:1915-1927 [PMID: 17494925 DOI:
10.1056/NEJMoa061741]
Garland SM, Hernandez-Avila M, Wheeler CM, Perez G,
Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M,
19 Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson M,
Boslego J, Sattler C, Barr E, Koutsky LA. Quadrivalent vac-
cine against human papillomavirus to prevent anogenital
diseases. N Engl J Med 2007; 356: 1928-1943 [PMID: 17494926
DOI: 10.1056/NEJMoa061760]
20 Wheeler CM, Kjaer SK, Sigurdsson K, Iversen OE, Hernan-
dez-Avila M, Perez G, Brown DR, Koutsky LA, Tay EH,
Garca P, Ault KA, Garland SM, Leodolter S, Olsson SE,
Tang GW, Ferris DG, Paavonen J, Steben M, Bosch FX, Dill-
ner J, Joura EA, Kurman RJ, Majewski S, Muoz N, Myers
21 ER, Villa LL, Taddeo FJ, Roberts C, Tadesse A, Bryan J, Lu-
pinacci LC, Giacoletti KE, James M, Vuocolo S, Hesley TM,
Barr E. The impact of quadrivalent human papillomavirus
(HPV; types 6, 11, 16, and 18) L1 virus-like particle vaccine
on infection and disease due to oncogenic nonvaccine HPV
types in sexually active women aged 16-26 years. J Infect Dis
2009; 199: 936-944 [PMID: 19236277 DOI: 10.1086/597309]
ACIP Adult Immunization Work Group, Bridges CB, Woods
L, Coyne-Beasley T. Advisory Committee on Immunization
22
23
WJCO|www.wjgnet.com
McGraw SL et al . Prevention and screening of cervical cancer
Practices (ACIP) recommended immunization schedules for
adults aged 19 years and older- United States, 2013. MMWR
Surveill Summ 2013; 62 Suppl 1: 9-19 [PMID: 23364303]
Brankovic I, Verdonk P, Klinge I. Applying a gender lens on
24 human papillomavirus infection: cervical cancer screening,
HPV DNA testing, and HPV vaccination. Int J Equity Health
2013; 12:14 [PMID: 23394214 DOI: 10.1186/1475-9276-1214]
Calloway C, Jorgensen CM, Saraiya M, Tsui J. A content
analysis of news coverage of the HPV vaccine by U.S.
25 newspapers, January 2002-June 2005. J Womens Health
(Larchmt) 2006; 15: 803-809 [PMID: 16999634 DOI: 10.1089/
jwh.2006.15.803]
Saslow D, Castle PE, Cox JT, Davey DD, Einstein MH, Fer-
ris DG, Harper DM, Kinney W, Moscicki AB, Noller KL,
Wheeler CM, Ades T, Andrews KS, Doroshenk MK, Kahn
26 KG, Schmidt C, Shafey O, Smith RA, Partridge EE; Gyeno-
cologic Cancer Advisory Group, Garcia F. American Cancer
Society Guideline for human papillomavirus (HPV) vaccine
use to prevent cervical cancer and its precursors. CA Cancer
J Clin 2007; 57: 7-28 [PMID: 17237032 DOI: 10.3322/canj-
clin.57.1.7]
Casper MJ, Carpenter LM. Sex, drugs, and politics: the HPV
vaccine for cervical cancer. Sociol Health Illn 2008; 30: 886-899
[PMID: 18761509]
Leader AE, Weiner JL, Kelly BJ, Hornik RC, Cappella JN.
Effects of information framing on human papillomavirus
27 vaccination. J Womens Health (Larchmt) 2009; 18: 225-233
[PMID: 19183094 DOI: 10.1089/jwh.2007.0711]
Hull SC, Caplan AL. The case for vaccinating boys against
human papillomavirus. Public Health Genomics 2009; 12:
28 362-367 [PMID: 19684448 DOI: 10.1159/000214926]
Taira AV, Neukermans CP, Sanders GD. Evaluating human
papillomavirus vaccination programs. Emerg Infect Dis 2004;
10: 1915-1923 [PMID: 15550200 DOI:10.3201/eid1011.040222]
Schiffman M, Castle PE. The promise of global cervical-
29 cancer prevention. N Engl J Med 2005; 353: 2101-2104 [PMID:
16291978]
Ladner J, Besson MH, Hampshire R, Tapert L, Chirenje
M, Saba J. Assessment of eight HPV vaccination programs
30
implemented in lowest income countries. BMC Public Health
2012; 12: 370 [PMID: 22621342 DOI: 10.1186/1471-2458-12-3
70]
31 Saslow D, Solomon D, Lawson HW, Killackey M, Kulasin-
gam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wil-
bur DC, Wentzensen N, Downs LS, Spitzer M, Moscicki AB,
Franco EL, Stoler MH, Schiffman M, Castle PE, Myers ER.
32 American Cancer Society, American Society for Colposcopy
and Cervical Pathology, and American Society for Clinical
Pathology screening guidelines for the prevention and early
detection of cervical cancer. CA Cancer J Clin ; 62: 147-172
[PMID: 22422631 DOI: 10.3322/caac.21139]
Fisher JW, Brundage SI. The challenge of eliminating cervi-
33 cal cancer in the United States: a story of politics, prudish-
ness, and prevention. Women Health 2009; 49: 246-261 [PMID:
19533513 DOI: 10.1080/03630240902915101]
Peterson NB, Murff HJ, Cui Y, Hargreaves M, Fowke JH.
Papanicolaou testing among women in the southern United
States. J Womens Health (Larchmt) 2008; 17: 939-946 [PMID:
18582173 DOI: 10.1089/jwh.2007.0576]
Arbyn M, Bergeron C, Klinkhamer P, Martin-Hirsch P,
Siebers AG, Bulten J. Liquid compared with conventional
cervical cytology: a systematic review and meta-analysis.
Obstet Gynecol 2008; 111: 167-177 [PMID: 18165406 DOI:
34 10.1097/01.AOG.0000296488.85807.b3]
Moyer VA. Screening for cervical cancer: U.S. Preventive
Services Task Force recommendation statement. Ann Intern
Med 2012; 156: 880-891, W312 [PMID: 22711081 DOI: 10.732
6/0003-4819-156-12-201206190-00424]
35 Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM,
Rozendaal L, Heideman DA, Verheijen RH, Bulk S, Verweij
36
37
38
751 October 10, 2014|Volume 5|Issue 4|
 McGraw SL et al . Prevention and screening of cervical cancer
W, Snijders PJ, Meijer CJ. HPV DNA testing in population-
based cervical screening (VUSA-Screen study): results and
implications. Br J Cancer 2012; 106: 975-981 [PMID: 22251922
DOI: 10.1038/bjc.2011.581]
Stoler MH, Castle PE, Solomon D, Schiffman M. The ex-
39 panded use of HPV testing in gynecologic practice per AS-
CCP-guided management requires the use of well-validated
assays. Am J Clin Pathol 2007; 127: 335-337 [PMID: 17276947]
Vetter KM, Geller SE. Moving forward: human papillo-
mavirus vaccination and the prevention of cervical cancer.
40 J Womens Health (Larchmt) 2007; 16: 1258-1268 [PMID:
18001182 DOI:10.1089/jwh.2007.0493.]
Sankaranarayanan R, Budukh AM, Rajkumar R. Effective
screening programmes for cervical cancer in low- and mid-
dle-income developing countries. Bull World Health Organ
41 2001; 79: 954-962 [PMID: 11693978]
Sahasrabuddhe VV, Bhosale RA, Kavatkar AN, Nagwanshi
CA, Joshi SN, Jenkins CA, Shepherd BE, Kelkar RS, Sahay
S, Risbud AR, Vermund SH, Mehendale SM. Comparison
of visual inspection with acetic acid and cervical cytology
42 to detect high-grade cervical neoplasia among HIV-infected
women in India. Int J Cancer 2012; 130: 234-240 [PMID:
21387289 DOI: 10.1002/ijc.25971]
Wiwanitkit V. Screening for cervical cancer: which com-
mon technique is the most cost-effective choice? Asian Pac J
Cancer Prev 2009; 10: 531-532 [PMID: 19640204]
Shastri SS, Dinshaw K, Amin G, Goswami S, Patil S, Chi-
noy R, Kane S, Kelkar R, Muwonge R, Mah C, Ajit D,
Sankaranarayanan R. Concurrent evaluation of visual, cyto-
43
logical and HPV testing as screening methods for the early
detection of cervical neoplasia in Mumbai, India. Bull World
Health Organ 2005; 83: 186-194 [PMID: 15798842]
44 Cuzick J, Arbyn M, Sankaranarayanan R, Tsu V, Ronco
G, Mayrand MH, Dillner J, Meijer CJ. Overview of human
papillomavirus-based and other novel options for cervical
cancer screening in developed and developing countries.
Vaccine 2008; 26 Suppl 10: K29-K41 [PMID: 18847555 DOI:
10.1016/j.vaccine.2008.06.019]
Qiao YL, Sellors JW, Eder PS, Bao YP, Lim JM, Zhao FH,
Weigl B, Zhang WH, Peck RB, Li L, Chen F, Pan QJ, Lorincz
45 AT. A new HPV-DNA test for cervical-cancer screening in
developing regions: a cross-sectional study of clinical ac-
curacy in rural China. Lancet Oncol 2008; 9: 929-936 [PMID:
18805733 DOI: 10.1016/S1470-2045(08)70210-9]
Yang HP, Walmer DK, Merisier D, Gage JC, Bell L, Rang-
wala S, Shrestha N, Kobayashi L, Eder PS, Castle PE. A pilot
analytic study of a research-level, lower-cost human papillo-
46 mavirus 16, 18, and 45 test. J Virol Methods 2011; 176: 112-114
[PMID: 21640138 DOI: 10.1016/j.jviromet.2011.05.024]
ACOG Committee on Practice Bulletins--Gynecology.
ACOG Practice Bulletin no. 109: Cervical cytology screening.
Obstet Gynecol 2009; 114: 1409-1420 [PMID: 20134296 DOI:
10.1097/AOG.0b013e3181c6f8a4]
Saslow D, Solomon D, Lawson HW, Killackey M, Kulasin-
gam SL, Cain J, Garcia FA, Moriarty AT, Waxman AG, Wil-
47 bur DC, Wentzensen N, Downs LS Jr, Spitzer M, Moscicki
AB, Franco EL, Stoler MH, Schiffman M, Castle PE, Myers
ER; American Cancer Society; American Society for Colpos-
copy and Cervical Pathology; American Society for Clinical
48
49
WJCO|www.wjgnet.com
Patholog. American Cancer Society, American Society for
Colposcopy and Cervical Pathology, and American Society
for Clinical Pathology screening guidelines for the preven-
tion and early detection of cervical cancer. Am J Clin Pathol
2012; 137: 516-542 [PMID: 22431528 DOI: 10.1309/AJCPTG-
D94EVRSJCG]
Committee on Practice Bulletins-Gynecology. ACOG Prac-
tice Bulletin Number 131: Screening for cervical cancer. Obstet
50
Gynecol 2012; 120: 1222-1238 [PMID: 23090560 DOI: 10.1097/
AOG.0b013e318277c92a]
Smith RA, Cokkinides V, Brooks D, Saslow D, Brawley
OW. Cancer screening in the United States, 2010: a review
of current American Cancer Society guidelines and issues in
51
cancer screening. CA Cancer J Clin 2010; 60: 99-119 [PMID:
20228384 DOI: 10.3322/caac.20063]
Vijayaraghavan A, Efrusy MB, Mayrand MH, Santas CC,
Goggin P. Cost-effectiveness of high-risk human papilloma-
virus testing for cervical cancer screening in Qubec, Cana-
da. Can J Public Health 2010; 101: 220-225 [PMID: 20737813]
52 Koliopoulos G, Arbyn M, Martin-Hirsch P, Kyrgiou M,
Prendiville W, Paraskevaidis E. Diagnostic accuracy of hu-
man papillomavirus testing in primary cervical screening:
a systematic review and meta-analysis of non-randomized
studies. Gynecol Oncol 2007; 104: 232-246 [PMID: 17084886]
53 Saslow D, Runowicz CD, Solomon D, Moscicki AB, Smith
RA, Eyre HJ, Cohen C. American Cancer Society guideline
for the early detection of cervical neoplasia and cancer. CA
Cancer J Clin 2002; 52: 342-362 [PMID: 12469763]
Rodrguez AC, Schiffman M, Herrero R, Hildesheim A,
Bratti C, Sherman ME, Solomon D, Guilln D, Alfaro M,
54 Morales J, Hutchinson M, Katki H, Cheung L, Wacholder
S, Burk RD. Longitudinal study of human papillomavirus
persistence and cervical intraepithelial neoplasia grade 2/3:
critical role of duration of infection. J Natl Cancer Inst 2010;
102: 315-324 [PMID: 20157096 DOI: 10.1093/jnci/djq001]
55 Fox J, Remington P, Layde P, Klein G. The effect of hyster-
ectomy on the risk of an abnormal screening Papanicolaou
test result. Am J Obstet Gynecol 1999; 180: 1104-1109 [PMID:
10329862]
Cuzick J, Castan A, Sasieni P. Predicted impact of vac-
cination against human papillomavirus 16/18 on cancer in-
cidence and cervical abnormalities in women aged 20-29 in
the UK. Br J Cancer 2010; 102: 933-939 [PMID: 20104226 DOI:
10.1038/sj.bjc.6605528]
56
Wright TC, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ,
Solomon D. 2006 consensus guidelines for the management
of women with abnormal cervical screening tests. J Low Ge-
nit Tract Dis 2007; 11: 201-222 [PMID: 17917566]
57 Kjr SK, Frederiksen K, Munk C, Iftner T. Long-term ab-
solute risk of cervical intraepithelial neoplasia grade 3 or
worse following human papillomavirus infection: role of
persistence. J Natl Cancer Inst 2010; 102: 1478-1488 [PMID:
20841605 DOI: 10.1093/jnci/djq356]
Khan MJ, Castle PE, Lorincz AT, Wacholder S, Sherman M,
Scott DR, Rush BB, Glass AG, Schiffman M. The elevated
58 10-year risk of cervical precancer and cancer in women with
human papillomavirus (HPV) type 16 or 18 and the possible
utility of type-specific HPV testing in clinical practice. J Natl
Cancer Inst 2005; 97: 1072-1079 [PMID: 16030305]
59
60
P- Reviewer: Badano I, Harper DM, Thulaseedharan JV, Yokoya-
ma Y S- Editor: Ji FF L- Editor: A E- Editor: Lu YJ
752 October 10, 2014|Volume 5|Issue 4|
 Published by Baishideng Publishing Group Inc
8226 Regency Drive, Pleasanton, CA 94588, USA
Telephone: +1-925-223-8242
Fax: +1-925-223-8243
E-mail: bpgoffice@wjgnet.com
Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx
http://www.wjgnet.com
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013

HUBUNG AN PEM AKAI AN KON TR ASEPSI H ORMO N AL D AN

NON HO RMO N AL DENG AN KEJ AD IAN KAN KER SER VIKS
DI R U ANG D ATAS BLU , PROF, Dr, R . D. KAN DOU
M ANADO

Sarwenda Abdullah
Jeavery Bawotong
Rivelino Hamel
Program Studi Ilmu KeperawatanFakultas KedokteranUniversitas Sam Ratulangi
Manado
Emai l: Sarwenda.abdullah@yahoo.com

ABSTRACT : Cervical Cancer is the tumor malignant epithelial cells derived from
squamous. Based on the data Globacan, International Agency for Research on cancer (IARC)
in 2002, pathology examination in one of Indonesia declared most cancers are cervical cancer.
This disease is a major cause of cancer death in women, even every year about a quarter of a
million women die from this disease. Research is done in the hospital room D upper, BLU.
Prof. Dr. R. D. Kandou Manado To The Effect to know relationship hormonal contraceptive
use and non-hormonal with cervical cancer incidence. This observasional Type with Method
cases control. Sample taken using Quota sample as much 42 people which consists of a group
of cases (cervical cancer +) and control group (cervical cancer is not -). Observasional results
of this study indicate that the use of 21 hormonal contraceptives 18 people cervical cancer +
and 3 cervical cancer is not -. Meanwhile to of 21 non-hormonal contraceptives 2 people
cervical cencer + and 19 people cervicak cancer is not-.
Based on the statistic test conducted, there was a significant association with contraceptive
use hormone and non hormone with cancer cervical incidence, where the value p =0,00 which
means that (p<0,05) wiwth the value OR 0,18. Thus it can be concluded contraceptive
hormone more risk 0,18 times compared with contraceptive non-hormonal.
Key Words: Contraceptive Hormonal and Non-Hormone, Cervical Cancer.

ABSTRAK : Kanker serviks adalah tumor ganas primer yang berasal dari sel epitel
skuamosa. Berdasarkan data Globocan, International Agency for Research on Cancer (IARC)
tahun 2002, hasil pemeriksaan patologi di Indonesia menyatakan salah satu kanker terbanyak
adalah kanker serviks. Penyakit ini merupakan penyebab kematian utama kanker pada wanita,
bahkan tiap tahunnya sekitar seperempat juta wanita meninggal karena penyakit ini.
Penelitian ini dilakukan di ruang inap D atas BLU. RSUP. Prof. Dr. R. D Kandou Manado
dengan tujuan untuk mengetahui hubungan pemakaian kontrasepsi hormonal dan non
hormonal dengan kejadian kanker serviks. Jenis penelitian ini adalah observasional analitik
dengan Metode Kasus Kontrol. Sampel diambil menggunakan Quota sampel sebanyak 42
orang yang terdiri dari kelompok kasus (kanker serviks +) dan kelompok kontrol (tidak
kanker serviks -). Hasil penelitian ini menunjukan bahwa dari 21 pemakaian kontrasepsi
hormonal 18 orang kanker serviks + dan 3 tidak kanker serviks -. Sedangkan pada dari 21
pemakaian kontrasepsi non hormonal 2 kanker serviks + dan 19 tidak kanker serviks -.
Berdasarkan uji statistik yang dilakukan, ada hubungan yang bermakna dengan pemakaian
kontrasepsi hormonal dan non hormonal dengan kejadian kanker serviks dimana nilai p=0,00
yang artinya (p<0,05) dengan nilai OR 0,18. Sehingga dapat disimpulkan bahwa kontrasepsi
hormonal dan non hormonal lebih berisiko 0,18 kali.
Kata kunci : Kontrasepsi Hormonal dan Non Hormonal, Kanker Serviks.

1
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013
PENDAHULUAN
World Health Organization (WHO)
menyatakan bahwa penyakit kanker
merupakan masalah kesehatan di berbagai
Negara termasuk Indonesia. Berdasarkan
data Globocan, International Agency for
Research on Cancer (IARC) tahun 2002,
Di Indonesia, hasil pemeriksaan patologi
menyatakan lima kanker terbanyak adalah
kanker leher rahim, payudara, kelenjar
getahbening, kulit dan nasofaring
(Harianto, 2004).
Indonesia sebagai salah satu
Negara berkembang yang mempunyai
beberapa masalah kependudukan. Jumlah
kelahiran hidup di seluruh rumah sakit di
Indonesia pada tahun 2006 adalah 116.991
kelahiran. Upaya untuk menekan angka
kelahiransalahsatunyadengan
menurunkan tingkat kelahiran yaitu
melalui program keluarga berencana
(Wiknjosastro, 2005).
Pemberianlayanankeluarga
berencana hendaknya dipandang sebagai
suatu layanan kesehatan reproduksi wanita
dalam konteks yang lebih luas. Layanan
keluarga berencana berkualitas tinggi
mencakup penyediaanpilihan alat
kontrasepsi yang aman dan sesuai bagi
wanita (Wulansari, 2007).
Kontrasepsisuntikuntuk
kebutuhan keluarga berencana di Indonesia
terus berkembang dari tahun ke tahun
dengan berbagai jenis preparat kontrasepsi
suntik yang tersedia. Pada tahun 2001
WHO menyatakan bahwa prevalensi
penggunaankontrasepsisuntikdi
Indonesia sebesar 10% sedangkan di
seluruh dunia adalah 2%.1 Kontrasepsi
suntik(Depo-Provera)DMPA
danCyclofem (kombinasi DMPA dan
Estradiol sipionate) sering digunakan
karena memiliki kelebihan-kelebihan
antara lain: dapat dilakukan di luar klinik,
kemungkinan salah atau lupa kecil, jangka
waktupemakaiancukuplama,
reversibilitastinggidansebagian
masyarakat masih menganggap pemberian
obat secara suntik merupakan cara yang
paling mujarab (Harianto, 2004).
2
Kaitan hormon-hormon tertentu
dengan perkembangan kanker tertentu
telahterbukti.Hormonbukanlah
karsinogen, tetapi dapat mempengaruhi
karsinogenesis.Hormondapat
mengendalikanataumenambah
pertumbuhan tumor. Dasar pemberian
terapi hormon dan beberapa terapi
pembedahan-hipofisioktomidan
ooferoktomi adalah prinsip karsinogenesis
ini Juga telah terbukti bahwa jaringan yang
responsiveterhadap endokrin-seperti
payudara, endometrium, dan prostat tidak
memperolehkanker,kecualijika
distimulasiolehgrowth-promothing
hormone. Estrogen telah dikaitkan dengan
adenokarsinoma pada vagina, payudara,
uterus, dan tumor hepatic (Mary 2008).
Data dari Badan Koordinasi
Keluarga Berencana Nasional (BKKBN) di
Indonesia tahun 2000, hanya 54,84%
perempuan reproduksi yang memakai
kontrasepsi dan metode KB yang
terpopuler adalah suntikan (40,88%), pil
(28,48%),danAKDR(13,84%)
(Suwiyoga, 2004). Harian kompas
menyebutkan bahwa suntik hormonal
menjadi pilihan mayoritas ibu-ibu.
Kanker seviks adalah tumor ganas
primer yang berasal dari sel epitel
skuamosa. Sebelum terjadinya kanker,
akan didahului oleh keadaan yang disebut
lesi prakanker atau neoplasia intraepitel
serviks (NIS). Sebagian besar penderita
kanker serviks datang berobat pada
stadium lanjut, karena pada stadium awal
penyakit ini tidak menimbulkan gejala.
Penyakit ini merupakan penyebab
kematian utama kanker pada wanita di
negara-negaraberkembangtermasuk
Indonesia, bahkan tiap tahunnya sekitar
seperempat juta wanita meninggal karena
penyakit ini (Khasbiyah, 2004).
Penyakit kanker serviks ini belum
diketahui penyebabnya secara pasti,
sehingga sulit untuk dilakukan pencegahan
primer. Penyebabnya diduga antara lain
melakukan hubungan seksual pertama kali
di bawah umur 20 tahun, pasangan seksual
dua orang atau lebih, cerai atau pisah
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013
dengan hubungan seksual yang tidak stabil,
merokok, higiene perorangan yang rendah,
kemiskinan, melahirkan anak pada usia
muda, rangsangan terus-menerus pada
leher rahim misalnya pada frekuensi koitus
yang tinggi, peradangan, paritas lebih dari
tiga dan adanya bahan-bahan mutagen
yang diduga dapat merubah sel-sel di
jaringan rahim secara genetik misalnya
sperma yang mengandung bahan rokok,
penggunaankontrasepsihormonal,
komplemen histon, mikoplasma, klamidia,
virus herpes simpleks (HSV 2), human
papiloma virus tipe 16,18,31 (HPV 16, 18,
31), trikomonas vaginalis (Rauf, 2006).
Terjadinya pemaparan estrogen
dapat disebabkan oleh penggunaan
kontrasepsi hormonal yang mengandung
kombinasi hormon yaitu estrogen dan
progesteron. Di Indonesia penggunaan
hormon sebagai alat kontrasepsi sudah
populer dalam masyarakat. Pemakai
kontrasepsi hormonal terbanyak adalah
jenis suntikan dan pil (Harianto, 2004).
Dari hasil observasi di ruang inap
D atas BLU. RSUP. Prof. Dr. R. D.
Kandou Manado jumlah penyakit kanker
serviks dari bulan September 2012-bulan
april 2013 terdapat 48 pasien yang dirawat
inap, sesuai dengan registrasi pasien.
Dari uraian diatas peneliti ingin
mempelajari lebih dalam tentang hubungan
pemakaian kontrasepsi hormonal dan non
hormonal terhadap kejadian kanker serviks
karena salah satu efek samping dari
kontrasepsi hormonal dan non hormonal
yaitu meningkatkan kemungkinan kejadian
kanker serviks. Penelitian ini bertujuan
untuk mengetahui hubungan pemakaian
kontrasepsi hormonal dan non hormonal
dengan kejadian kanker serviks.
METODE PENELITIAN
Jenispenelitianadalahpenelitian
observasional analitik dengan pendekatan
Case Control Study (kasus kontrol).
Penelitian ini telah dilaksanakan di Ruang
Inap D Atas RSUP Prof. Dr. R. D. Kandou
Manado. Penelitian ini telah dilaksanakan
pada tanggal 3 s/d 28 juni 2013.
3
Populasi yaitu semua pasien yang
dirawat diruang inap D atas pada 1 tahun
terakhir dan Sampel dalam penelitian ini
dibagi dalam dua kelompok, yaitu kasus
adalah semua pasien yang dirawat
diruangan D atas 1 tahun terakhir
yang dinyatakan menderita kanker serviks
berdasarkan catatan rekammedik
sedangkan kontrol adalah semua
pasien yang dirawat diruangan D atas yang
dinyatakan tidak menderita kanker serviks
ataupun kanker lainnya berdasarkan
catatan buku diagnosa dan mempunyai
data lengkap mengenai variabel yang
diteliti. Teknik pengambilan sampel dalam
penelitian ini yaitu quota sampling,teknik
pengambilan sampel sesuai dengan
populasi yang di dapat di Ruang Inap D
Atas RSUP .Prof. Dr. R. D. Kandou
Manado berjumlah 48 pasien kanker
serviks. Sampel di ambil berdasarkan
kriteria inklusi dan eksklusi. Kriteria
Inklusi : Kelompok kasus,Wanita yang
menggunakan kontrasepsi hormonal dan
non hormonal dan mengalami kejadian
kanker serviks, wanita yangtidak
menggunakan kontrasepsi hormonal dan
non hormonal mengalami kejadian kanker
serviks. Kelompok kontrol , Wanita yang
menggunakan kontrasepsi hormonal dan
non hormonal dan mengalami kejadian
kanker serviks, Wanita yang tidak
menggunakan kontrasepsi hormonal dan
non hormonal mengalami kejadian kanker
serviks. Kriteria Eksklusi : Kelompok
kasus, Wanita yang tidak menggunakan
kontrasepsi hormonaldan non hormonal
tidak mengalami kejadian kanker serviks.
Kelompok kontrol : Wanita yang tidak
menggunakan kontrasepsi hormonal dan
non hormonal tidak mengalami kejadian
kanker serviks.
Rumus pengambilan sampel :
. . .
n= .(
). . .
Keterangan :
n: Besar Sampel
p:Estimatorproporsi
populasi jika tidak diketahui dianggap
(50%)
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013
q: 1- p (100% - p)
Z: Harga kurva normal yang
tergantung dari harga (Z 0.05 =
1,95).
N: Toleransi kesalahan yang
dipilih (d=0,05).
n=
(.) , ,
)(. )
, ( ( . )( .
= 42
Dari rumus sampel ini didapat
sampel 42 sampel yang akan diteliti.
Instrument dalam penelitian
ini melakukan Observasi yaitu
checklist dan rating scale dari
registrasi pasien yang dirawat di ruang
Inap D atas1 tahun terakhir, yang
berisi pertanyaan tentang data umum
responden.
Tahap Persiapan : Memilih tempat
penelitian, Malakukan koordinasi
dengantempatpenelitian,
Mendapatkan izin studi pendahuluan,
Melakukan studi pendahuluan dan
penjajakan awal untuk menentukan
masalah, Melakukan studi keputusan,
Menyusunproposalpenelitian,
Seminar proposal, Perbaikan proposal.
Tahap Pelaksanaan : Mendapatkan
izin penelitian, Persetujuan responden,
Pengumpulan data lewat observasi
atau checklist, Pengolahan data dan
anilisis data.
Tahap Akhir : Penyusunan laporan
penelitian, Seminar hasil penelitian,
Perbaikan hasil siding, Pengadaan
lampiran penelitian.
Pengolahan Data : editing, koding,
dan menggunakan analisis Univarit
dan Bivariat.
Dalam melakukan penelitian,
peneliti perlu mendapatkan adanya
rekomndasi dariinstitusinya atau
pihak lain dengan mengajukan
permohonanizinkepada
institusi/lembaga tempat penelitian.
Setelah mendapat persetujuan barulah
melakukanpenelitiandengan
Tabel 8. Distribusi responden berdasarkan
menekankan masalah etika yang
meliputi:Informedconcent,
Anonymity (tanpa mana), dan
Confidentiality.
HASIL DAN PEMBAHASAN
Berdasarkananalisis hubungan
pemakaian kontrasepsi hormonal dan
non hormonal dengan kejadian kanker
) serviks diperoleh dari 42 responden
dimana semuanya menggunakan
kontrasepsi hormonal dan non
hormonal,darihasilanalisa
berdasarkanumurresponden
menunjukan bahwa paling banyak
responden berada pada kelompok
umur 41-57 dan paling sedikit berada
padakelompokumur31-35.
Berdasarkantingkatpendidikan
dimana responden yang paling banyak
pada tingkat SMA dan paling sedikit
pada tingkatS1. Berdasarkan
kelompok pekerjaan responden paling
banyak berada pada kelompok IRT
dan paling sediki berada pada
kelompok pensiunan, lihat pada tabel
3. Sedangkan berdasarkan paritas
paling banyak rsponden memiliki 2
anak dan paling sedikit 6 anak.
Berdasarkanfrekuensidistribusi
analisa data pemakaian kontrasepsi
hormonal menunjukan paling banyak
responden yang kanker serviks
dimanaresponden berada pada
pemakaian kontrasepsi pil, dan paling
sedikit pemakaian kontrasepsi suntik
dan implant. Sedangkan Berdasarkan
distribusiferkuensipemakaian
kontrasepsinonhormonal
menunjukan paling banyak responden
berada pada pemakaian kontrasepsi
IUD dan paling sedikit system
kalender dan kondom.
4
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013
Tabel. 8 Pemakaian Kontrasepsi Hormonal
Dan Non Hormonal Dengan Kejadian
Kanker Serviks
Kejadian
Kontrasep Tota P Nila
si Tidak l i
Kanke Kanke
OR
r r
Servik Servik
s s
3 18
Hormonal 21
0,0 0,18
0 untuk ibu dengan pemakaian alat
Non 19 2 21
Hormonal
Total 22 20 42 100
Sumber : Data Primer 2013
Sebelum dilakukan uji Chi-square, terlebih
dahulu ditampilkan tabulasi silang (cross
tab) yang menggambarkan penyebaran data.
Tabulasi silang tersebut berdimensi 2x2
atau disebut tabel kontingensi 2x2. dapat
dilihat bahwa 42 responden yang di bagi
dalam dua kelompok yaitu kasus dan
kontrol, dimana kelompok kasus kanker
serviks dan kelompok kontrol tidak kanker
serviksdengan pemakaian kontrasepsi
hormonal sebanyak 18 kasus, dimana ibu
berada pada kelompok umur 23-57 dan
memiliki paritas 2-6, Sedangkan pada
pemakaiankontrasepsi non hormonal
sebanyak 2 kasus, dimana ibu berdada pada
kelompok umur 40-45 dan memiliki paritas
4-5.
Setelah dilakukan uji statistik
dengan uji chi-square di dapatkan bahwa
ada hubungan pemakaian kontrasepsi
hormonal dengan kejadian kanker serviks.
Dlihat pada nilai p. Hasil analisis Chi-
square pada tabel kontingensi 2x2 dengan
hubungan pemakaian kontrasepsi hormonal
dengan kejadian kanker serviks dengan
derajat kebebasan (df) 1 dan tingkat
signifikansi () sebesar 5% (0,05), maka H0
di tolak. Dengan demikian, maka
kesimpulannya adalah pada tingkat
kepercayaan 95% dan 0,05, terdapat
hubungan yang signifikan antara pemakaian
alat kontrasepsi hormonal dengan kejadian
kanker serviks.Hasil analisis statistika
5
dengan menggunakan uji chi-square di
peroleh bahwa ada hubungan antara
pemakaian kontrasepsi hormonal dengan
kejadian kanker serviks di ruang inap D atas
BLU, Prof. dr. R. D. Kandou Manado.
Setelah dilakukan perhitungan Odds Ratio,
pada pemakaian kontrasepsi hormonal
didapati nilai OR sebesar 0,18. Besar nilai
OR>1, ini menunjukkan bahwa pemakaian
alat kontrasepsi hormonal merupakan faktor
penyebab terjadinya kanker serviks.
Kemungkinan terjadinya kanker serviks
kontrasepsi hormonal adalah 0,18 kali. Di
bandingkan dengan pemakaian kontrasepsi
non hormonal.
Hasil penelitian tersebut relevan dengan
teori yang dikemukakan oleh Ali (2002),
bahwa pada penggunaan kontrasepsi
hormonal tidak jarang pula ditemukan
displasia serviks, sehingga selama masih
menggunakan kontrasepsi hormonal sangat
disarankan untuk melakukan pemeriksaan
ginekologiksecarateratur,seperti
pemeriksaan papsmear setiap 6 bulan
sampai 1 tahun sekali.
Hasil penelitian ini berkaitan
dengan penelitian yang telah dilakukan oleh
Mutia Rissa Pratiwi yaitu Ada Pengaruh
Pemakaian Kontrasepsi Estrogen Dan
Progesterone Dengan Kejadian Kanker
Serviks. Bahwa kemungkinan terjadinya
kanker leher rahim untuk pasien dengan
riwayat pemakaian kontrasepsi hormonal
kombinasi adalah 17,9 kali dibanding
dengan pasien yang tidak menggunakan
kontrasepsi hormonal kombinasi. Hal ini
berdasarkan dengan teori menurut Manuaba
bahwa salah satu peningkatan resiko kanker
serviks yaitu pemakaian KB Pil, dalam hal
ini KB Pil merupakan salah satu macam
dari alat kontrasepsi hormonal.
Berdasarkan hasil dan data
penelitian yang diperoleh dari 42 sampel
maka dapat disimpulkan bahwa pada
umumnya responden yang menggunakan
kontrasepsi hormonal lebih berisiko terkena
kanker serviks, melihat dampak yang terjadi
pada responden sebaiknya tenaga kesehatan
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013

memberikan informasibahwa pada penggunaan kontrasepsi hormonal, tidak

jarang pula ditemukan displasia serviks,

sehingga selama masih menggunakan

kontrasepsi hormonal sangat disarankan
untuk melakukan pemeriksaan ginekologik
secarateratur,sepertipemeriksaan
papsmear setiap 6 bulan sampai 1 tahun
sekali untuk deteksi dini kanker serviks.
Penelitianinimemilikibeberapa
keterbatasan, di antaranya pertanyaan dalam
lembar observasi yang dibuat oleh peneliti
kurang tajam untuk menganalisis adanya
hubungan antara pemakaian kontrasepsi
hormonal dengan non hormonal. Sebagai
contoh pertanyaan tentang pemakaian
kontrasepsi pil,suntik, implant, IUD dan
sebagainya yangditanyakanhanya
pemakaian saat ini bukan sewaktu sebelum
menderita Kanker serviks, selain itu lama
pemakaian serta apakah kontrasepsi pil
dipakai secara terus menerus atau diselingi
dengan kontrasepsi yang lainnya juga tidak
di tanyakan.

DAFTAR PUSATAKA
Ali, A, H, 2002. Kontrasepsi Hormonal.
Jakarta . YBP-SP. Glasier.
Harianto, Rina, M, dan Hery, S 2005,Risiko
penggunaan pil kontrasepsi kombinasi
terhadap kejadiankanker payudara pada
reseptorKBJakarta:MajalahIlmu
Kefarmasian,
KankerLeher
rahim(http://ejournal.akbidpurworejo.ac.id
/index.php/jkk1/article/view/43)
Diakses 5/3/2013 : 1:19 am
Rauf, Syarul, 2006. Penanggulangan
Kanker Leher Rahim. WIDI Cabang
Makassar.Edisi 4: 14-17.

Heriyanto.RisikoPenggunaanPil Sukaca. 2009. Penggunaan Kontrasepsi

Kontrasepsi Kombinasi Terhadap Kejadian
Kanker Payudara pada Reseptor KB
di Perjan RS Dr. Cipto Mangunkusumo.
April 2005
(www.jurnal.farmasi.ac.id.) diakses 6 mei
2013, 11:13 pm
PIL dalam jangka waktu. Jakarta. Sinar
baru.
Wiknjosastro H. 2005. Ilmu Kebidanan.
Jakarta: Yayasan Bina Pustaka Sarwono
Prawirodiharjo.

Mutia Rissa Pratiwi. 2010. Pengaruh Wulansari P, dkk. 2007. Ragam Metode
Pemakaian Alat Kontrasepsi Kombinasi Kontrasepsi. Jakarta: EGC.
Progesteron Estrogen Terhadap Kejadian

6
E-jurnal keperawatan (e-Kp) volume1 nomor1 agustus 2013