HUMAN PAPILLOMA VIRUS and CERVICAL CARCINOMA Roger J

HUMAN PAPILLOMA VIRUS Cervical cancer epidemiology • Coital exposure • Coitus at an early

HUMAN PAPILLOMA VIRUS • One of the most common STDs • 20 - 46%

HUMAN PAPILLOMA VIRUS 3 year study of college women : • 60% infected at

HUMAN PAPILLOMA VIRUS • CIN / HPV association in 76% of cases • HPV

HUMAN PAPILLOMA VIRUS • High risk (Oncogenic) 16, 18, 45, 56 • Low risk

HUMAN PAPILLOMA VIRUS • Infection induces cell proliferation and delay of cellular differentiation •

HUMAN PAPILLOMA VIRUS HPV oncogenes : - • E 6 • E 7 Binds

HUMAN PAPILLOMA VIRUS • High risk types have a high binding affinity for p

HUMAN PAPILLOMA VIRUS • Other cofactors Smoking • Other oncogenes Over expression of epidermal

HUMAN PAPILLOMA VIRUS Primary screening • 25% of high grade lesions are -ve for

HUMAN PAPILLOMA VIRUS Triage of mild dyskaryosis and borderline smears • Disease progression is

HUMAN PAPILLOMA VIRUS Treatment • Nothing worthwhile for the active infection • Vaccination

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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

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, 40 s • 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 E 6 and E 7

HUMAN PAPILLOMA VIRUS HPV oncogenes : - • E 6 • E 7 Binds to p 53 Binds to Retinoblastoma (RB) gene Tumour suppressor proteins are inactivated

HUMAN PAPILLOMA VIRUS • High risk types have a high binding affinity for p 53 and RB • p 53 expression blocks entry to the cell cycle until DNA damage is repaired • p 53 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