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HUMAN PAPILLOMA VIRUS and CERVICAL CARCINOMA. Roger J Rand. HUMAN PAPILLOMA VIRUS. Cervical cancer epidemiology Coital exposure Coitus at an early age Cervical morphology Metaplasia in young women . HUMAN PAPILLOMA VIRUS. One of the most common STDs 20 - 46% of young women.
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HUMAN PAPILLOMA VIRUS andCERVICAL CARCINOMA Roger J Rand
HUMAN PAPILLOMA VIRUS Cervical cancer epidemiology • Coital exposure • Coitus at an early age Cervical morphology • Metaplasia in young women
HUMAN PAPILLOMA VIRUS • One of the most common STDs • 20 - 46% of young women
HUMAN PAPILLOMA VIRUS 3 year study of college women :- • 60% infected at some time • Associated with :- younger age, more sexual partners, more sex, more alcohol • Mean duration of infection was 8 months • 34% resolved within 6 months • Only 11% resolved in the following 12 months • Persistence associated with :- High risk types, multiple types, not smoking
HUMAN PAPILLOMA VIRUS • CIN / HPV association in 76% of cases • HPV +ve women have a 9 fold higher incidence of CIN (higher still for high risk types) • High risk HPV types found in :- 32.7% No atypia 46% Mild atypia 60% High grade CIN
HUMAN PAPILLOMA VIRUS • High risk (Oncogenic) 16, 18, 45, 56 • Low risk 6,11,40s • Intermediate risk 31,33,35,51,52
HUMAN PAPILLOMA VIRUS • Infection induces cell proliferation and delay of cellular differentiation • This ability is dependent on the presence of the oncogenes E6 and E7
HUMAN PAPILLOMA VIRUS HPV oncogenes :- • E6 Binds to p53 • E7 Binds to Retinoblastoma (RB) gene Tumour suppressor proteins are inactivated
HUMAN PAPILLOMA VIRUS • High risk types have a high binding affinity for p53 and RB • p53 expression blocks entry to the cell cycle until DNA damage is repaired • p53 repression allows DNA mutations to accumulate and for subsequent cell transformation
HUMAN PAPILLOMA VIRUS • Other cofactors Smoking • Other oncogenes Over expression of epidermal growth factor receptor (EGFR) may allow for progression from low grade CIN
HUMAN PAPILLOMA VIRUS Primary screening • 25% of high grade lesions are -ve for HPV • Predictive value of a +ve test is relatively poor Therefore a useful addition, not a replacement for cytology (May prove be cost effective in older women in whom the prevalence of HPV declines)
HUMAN PAPILLOMA VIRUS Triage of mild dyskaryosis and borderline smears • Disease progression is more likely if high risk types are present
HUMAN PAPILLOMA VIRUS Treatment • Nothing worthwhile for the active infection • Vaccination