1. HPV Sample Taker Training South West Regional Cytology Training Centre Southmead Hospital Bristol

2. Human Papilloma Virus (HPV) How is it transmitted?How is it transmitted?

3. HPV Infection Lifetime risk of acquiring genital HPV is 80%Lifetime risk of acquiring genital HPV is 80% Most are asymptomaticMost are asymptomatic Infections are usually transientInfections are usually transient Most will clear within 12 monthsMost will clear within 12 months Some persistSome persist

4. Cervical cancer - Risk Persistent infection with high risk HPVPersistent infection with high risk HPV Integration of viral genes into host cell DNAIntegration of viral genes into host cell DNA Other co-factorsOther co-factors

5. Increases the risk HPV

6. Natural history of Cervical Cancer HPV DNA Epithelial cell E6 E7 Integrated DNA pRb p53

7. How does HPV affect the cells? Faulty cells Protective genes Cells stop multiplying and dividing Cell death Faulty cells HPV Protective genes Faulty cells continue to divide and multiply Cancer

9. High-risk HPV types that cause cervical cancer in Europe HPV type Percentage of cervical cancer cases caused by HPV type Cumulative percentage 1658.1%58.1% 1815.7%73.8% 334.4%78.2% 314.0%82.2% 452.9%85.1% 351.6%86.7% 581.2%87.9% 561.0%88.9% 520.6%89.5% 390.2%89.7% 510.2%89.9% 680.3%90.2% 590.1%90.3% Other1.4%91.7% No type identified 8.3%100% Adapted from Smith JS et al., 2007; Int J Cancer. 121(3):621-32.

10. HPV Triage & Test of Cure (TOC)

11. Triage & TOC Bristol since 2008Bristol since 2008 National Rollout April 2012National Rollout April 2012

12. HPV Testing Test detect presence of a range of different HR HPVTest detect presence of a range of different HR HPV Detects active infectionDetects active infection Very sensitiveVery sensitive Many women have HPV but no cervical abnormalityMany women have HPV but no cervical abnormality Very common infectionVery common infection

13. HPV Triage Triage women with minor/low grade abnormalityTriage women with minor/low grade abnormality Management determined by HPV resultManagement determined by HPV result

14. HPV Triage Borderline Changes/ Low grade abnormality HPV Test HPV Negative Routine recall HPV Positive Refer to colposcopy

15. HPV positive rates by age group and initial cytology result BorderlineMildTotal Age Grp No of women HPV + n (%) No of women HPV + n (%) No of women HPV + n (%) 25-34 3121 2144 (68.7) 2203 1964 (89.2) 5324 4108 (77.2) 35-49 2783 1165 (41.9) 1129 869 (77.0) 3912 2034 (52.0) 50-64 603 187 (31.0) 212 141 (66.5) 815 328 (40.2) Total 6507 3496 (53.7) 3544 2974 (83.9) 10051 6470 (64.4)

16. Test of Cure Women treated for CIN are tested to see if they no longer have active infection Management based on HPV test North Bristol NHS Trust/Avon Cervical screening programme

17. HPV Test Of Cure Negative/low grade TOC HPV Negative 3 year recall HPV Positive Refer back to colp Cervical sample taken post treatment of cervical abnormality

18. Test of cure – not eligible No proven CINNo proven CIN CancerCancer

19. HPV Primary Screening

20. HPV test as a primary screening test Primary screening for HPVPrimary screening for HPV Sample tested for HPV as the primary testSample tested for HPV as the primary test Being piloted in soma areas in EnglandBeing piloted in soma areas in England

21. HPV Primary Screening Pilot Sites BristolBristol LondonLondon NorwichNorwich ManchesterManchester LiverpoolLiverpool SheffieldSheffield

22. HPV primary screening Quantitative test, not subjectiveQuantitative test, not subjective People with an HPV negative test are less likely to have CIN3 or worse than people with a negative Pap test (NPV 93.8-99.7%)People with an HPV negative test are less likely to have CIN3 or worse than people with a negative Pap test (NPV 93.8-99.7%) HPV positive test identifies women at increased risk of subsequent CIN3+HPV positive test identifies women at increased risk of subsequent CIN3+

23. HPV Primary Screening Women who do not have HPV will have a degree of reassurance they will not develop cervical cancerWomen who do not have HPV will have a degree of reassurance they will not develop cervical cancer More sensitive first line test than cytology for the future vaccinated populationMore sensitive first line test than cytology for the future vaccinated population

24. Bristol Trial started Sept 2013Trial started Sept 2013 Only certain GP practices (20K women)Only certain GP practices (20K women) Information leaflets for invited womenInformation leaflets for invited women

25. HPV Primary Screening

26. Primary Screening Pilot Majority of samples are HPV negative No slide made for cytology (a few exceptions) About 20% of samples are HPV positive Cytology slide made & assessed

27. Primary screening pilot Women in follow up for inv ca/HIV+ will have annual HPV test HPV primary screening will not detect non- cervical lesions May miss some high grade lesions (no more than cytology would)

28. HPV Vaccination

29. Preventative vaccination confers protectionPreventative vaccination confers protection No therapeutic effect for existing infectionNo therapeutic effect for existing infection 2008 UK programme started (Cervarix)2008 UK programme started (Cervarix) –HPV 16 & 18 2011 – UK prog changed to Gardasyl2011 – UK prog changed to Gardasyl –HPV 16 & 18, 6 & 11

30. HPV Vaccination UK

31. HPV Vaccination Data Should be added to Exeter database for future cervical screeningShould be added to Exeter database for future cervical screening Will provide protection against some but not all cases of cervical cancerWill provide protection against some but not all cases of cervical cancer Cervical screening to continue to ensure protectionCervical screening to continue to ensure protection

32. Summary HPV Triage HPV Test of cure HPV Primary Screening trial HPV vaccination

33. Any questions?