INFEKSI VIRUS EPSTEIN-BARR SEBAGAI FAKTOR ETIOLOGI KARSINOMA NASOFARING

Oleh Nur Hidayah J500 050 007 Dian Ardiani Jati 7500 050 008
Pembimbing : dr.Iwan Setiawan, Sp.THT

Pendahuluan
Karsinoma nasofaring (KNF) adalah keganasan jenis karsinoma yang berasal dari epitel atau mukosa dan kripta yang melapisi permukaan nasofaring kanker yg paling sering di THT. Nasopharyngeal malignancies
SCCA (nasopharyngeal carcinoma) Lymphoma Salivary gland tumors Sarcomas

Anatomy
Anterior : nasal cavity Posterior : basis cranii and vertebral cervicalis 1,2 Inferior : oropharynx and palatum molle Lateral :
Tuba Eustachius Fossa Rosenmuller - most common location

Anatomy
Berhubungan dekat dg Foramen Basis cranii. Mucosa
Epithel transisional, peralihan antara :
Epitel squamous kompleks Epitel pseudokompleks columnar.

Dibawah epitel byk jaringan Lymphoid.

Epidemiology
Chinese native > Chinese immigrant > North American native
Both genetic and environmental factors

Genetic
HLA histocompatibility loci possible markers

Epidemiology
Environmental
Viruses
EBV- KNF type II and III HPV - possible factor pada type I

Nitrosamines ikan asin Others - polycyclic hydrocarbons, infeksi hidung kronis, hygiene yg kurang, ventilation yg tidak bagus.

Etiology Virus Epstein-Barr

Group : Group I (dsDNA) Family : Herpesviridae Subfamily: Gammaherpesvirinae Genus : Lymphocryptovirus Species : Human herpesvirus 4 (HHV-4)

Patofisiology
EBV merupakan virus DNA mampu menstimulasi limfosit B dan sel epitel faring. Masuk tubuh mll reseptor CR2/CD21 Punya beberapa Ag : VCA, EA, LMP, nuclear antigen dan Dnase. Dpt memicu timbulnya respon imun seluler maupun humoral.

Antibodi spesifik untuk EBV dalam tubuh IgA-anti VCA, IgG-anti EBV-EA sehingga dapat digunakan untuk memantau keberadaan virus EB didalam tubuh

Bukti kuat yg menunjukkan infeksi virus EB sebagai salah satu faktor etiologi utama dari KNF yaitu ditemukannya - DNA virus EB di sirkulasi darah - antigen virus EB (EBNA, LMP, ZEBRA) di dalam sel KNF - genom virus Epstein Barr dalam bentuk plasmid di jaringan KNF - DNA virus EB dan mRNA-EBV (EBERs) di sel kanker nasofaring.

Classification
WHO classes Type I - Karsinoma sel skuamosa dengan berkeratinisasi (25 %) Type II - Karsinoma sel skuamosa tanpa keratinisasi (12%) Type III - Karsinoma tanpa diferensiasi
60 % dari KNF, terbanyak pd usia muda.

Classification
Perbedaan antara type I dan types II & III
5 year survival live
Type I - 10% Types II, III - 50%

Resiko Recurren Jangka panjang, Type II &III Virus Penyebab :

Type I HPV (Human Papiloma Virus) Types II, III EBV (Ebstein-Barr Virus)

Clinical Presentation
Initial symptoms
unilateral HL Nyeri, pembesaran massa leher secara pelan2.

Larger lesions
Obstruksi hidung epistaxis Keterlibatan Nervi Cranialis.

Clinical Presentation
Xerophthalmia Facial pain n. Trigeminal Diplopia N. VI Ophthalmoplegia N. III, IV, dan VI
cavernous sinus or superior orbital fissure

CNs IX, X, XI, XII - extensive skull base

Presentasi Klinis
Pemeriksaan Nasopharyng
Fossa of Rosenmuller most common location Variable appearance - exophytic, submucosal NP bisa terlihat normal

Regional spread
Biasanya ipsilateral tapi bisa juga bilateral

Distant spread - rare (<3%), pulmo, hepar, tulang.

Role Of EBV
Infeksi Latent Bisa terjadi di Awal2 Kehidupan Definite role in types II & III
Full EBV genome present in all NPC epithelial cells

Variable role in type I

Associated in endemic regions, but not others Tobacco, Alcohol & HPV implicated
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Serological Markers
EBV in epithelial and B Lymphocyte cells
Humoral immune response multiple anti-EBV serology, includes:
IgG & IgA against VCA & EA Anti-EBNA IgG Antibodies against EBV replicator protein ZEBRA Circulating EBV DNA (by PCR) Oncogenes under investigation
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What is the role of EBV Titres

Potential uses of:
VCA, EA & EBV DNA

Diagnosis
VCA & EA

Diagnosis & Monitoring

EBV DNA

Peter Ross, Nasophayrngeal Carcinoma

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Laboratory evaluation
Special diagnostic tests (for types II & III)
IgA antibodies for viral capsid antigen (VCA) IgG antibodies for early antigen (EA)

Special prognostic test (for types II & III)

antibody-dependent cellular cytotoxicity (ADCC) assay
higher titers indicate a better long-term prognosis

Treatment
External beam radiation
Dose: 6500-7000 cGy Primary, upper cervical nodes, pos. lower nodes Consider 5000 cGy prophylactic tx of clinically negative lower neck

Adjuvant brachytherapy
mainly for residual/recurrent disease

Treatment
External beam radiation - complications
More severe when repeat treatments required Include
xerostomia, tooth decay ETD - early (SOM), later (patulous ET) Endocrine disorders - hypopituitarism, hypothyroidism, hypothalamic disfunction Soft tissue fibrosis including trismus Ophthalmologic problems Skull base necrosis

Treatment
Surgical management Mainly diagnostic - Biopsy
consider clinic bx if cooperative patient must obtain large biopsy clinically normal NP - OR for panendo and bx

Surgical treatment
primary lesion regional failure with local control ETD

Treatment
Surgical management Primary lesion
consider for residual or recurrent disease approaches
infratemporal fossa transparotid temporal bone approach transmaxillary transmandibular transpalatal

Treatment
Surgical management Regional disease
Neck dissection may offer improved survival compared to repeat radiation of the neck

ETD
BMT if symptomatic prior to XRT Post XRT
observation period if symptoms not severe amplification may be more appropriate

Treatment
Chemotherapy
Variety of agents Chemotherapy + XRT - no proven long term benefit Mainly for palliation of distant disease

Immunotherapy
Future treatment?? Vaccine??

Conclusion
Rare in North America, more common in China 40% overall survival at 5 years Complete H&P, careful otologic, neurologic, cervical and NP exams Three WHO types - all from NP epithelium Types II, III - better prognosis, EBV assoc. Treatment is primarily XRT

Diagnosis - Summary
Serology can provide an adjuvant test in the diagnosis of NPC More than one titre is required Biopsy + viral detection in biopsy is still the gold standard
There is insufficient evidence for serological diagnosis or screening alone

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