1. HUMAN PAPILLOMA VIRUS and CERVICAL CARCINOMA
Roger J Rand

2. Cervical cancer epidemiology
HUMAN PAPILLOMA VIRUS
Cervical cancer epidemiology
Coital exposure
Coitus at an early age
Cervical morphology
Metaplasia in young women

3. HUMAN PAPILLOMA VIRUS One of the most common STDs
% of young women

4. 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

5. 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

6. HUMAN PAPILLOMA VIRUS High risk (Oncogenic) 16, 18, 45, 56 Low risk
Intermediate risk
31,33,35,51,52

7. 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

8. HUMAN PAPILLOMA VIRUS HPV oncogenes :- E6 Binds to p53
E Binds to Retinoblastoma (RB) gene
Tumour suppressor proteins are inactivated

9. 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

10. HUMAN PAPILLOMA VIRUS Other cofactors Smoking Other oncogenes
Over expression of epidermal growth factor receptor (EGFR) may allow for progression from low grade CIN

11. 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)

12. HUMAN PAPILLOMA VIRUS Triage of mild dyskaryosis and borderline smears
Disease progression is more likely if high risk types are present

13. HUMAN PAPILLOMA VIRUS Treatment
Nothing worthwhile for the active infection
Vaccination