HPV and cervical screening Test of cure Dr Matt Hewitt

Cervical cancer in Ireland – key statistics 9th most frequently diagnosed cancer in women (278) 12th most common cause of cancer death in women (103) Average age diagnosis - 46 years Average age death - 56 years Survival in Ireland is slightly lower than the European average. The trends in mortality since 1978 show an increase of 1.5% per year. Ref: National Cancer Registry Ireland

Key points – prevention of deaths from cervical cancer Primary prevention Vaccination Secondary prevention Cervical cytology CervicalCheck screening programme Early Diagnosis Down staging of cancers at diagnosis Agreed assessment and referral for women with symptoms

CERVIX SQ – squamous epithelium COL – Columnar epithelium SQ COL COL

Acidic vagina Metaplasia

External os Glandular epithelium (Ectropion) New Sq Col Jun Transformation zone Area of metaplasia Native Sq Col Jun

HPV HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

Acidic vagina Metaplasia Acidic vagina Dysplasia

Natural history of HPV infection Transmission by sex Lifetime risk 80% - most within 18 months Exposure Transient Most resolve within 18 months Infection Less than 20% persist No antibodies detectable Persistence Virus integrates into host DNA Malignant Transformation Loss of tumour suppressor gene E2 Uncontrolled cells division CIN

Natural history of CIN Observe Treat (LLETZ)

Metaplasia Cancer CIN I CIN II CIN III

Use of HPV in screening In the management of women with low grade sears In the follow up of women who have had treatment Future use of HPV in screening HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

Low grade smears Very common Fill the colposcopy clinic with patients Majority of low grade CIN will resolve spontaneously Low grade CIN natural response to HPV infection Patient anxiety Cost How to overcome these problems? Use of HPV in low grade disease in colposcopy Use of HPV in primary care HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

Future screening protocols Incorporate HPV in primary care screening If Low grade smear and negative HPV avoid colp referral Advantages Cost saving Reduced anxiety in colposcopy referral Avoid unnecessary treatment HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85. Disadvantage Counselling women about HPV infection

Options for follow-up after treatment Cumulative incidence of CIN3+ Sensitivity of cytology is low with high false negatives Traditional schedules Compensate by repeated smears – annual for ten years HPV test with cytology has negative predictive value of> 90% Dillner, J. et al. BMJ 2008

Follow-up after treatment 6 month smear at Colposcopy 12 month smear 24 month smear 36 month smear 48 month smear 60 month smear 72 month smear 84 month smear 96 month smear 120 month smear Routine Recall Traditional strategy 6 Months HPV and Smear 18 months HPV and Smear Discharge to routine screening if double negative New strategy

HPV 16 and 18

Advantages of introducing the vaccine Reduced incidence of cervical cancer (adeno and squamous) Reduced incidence of genital warts Reduce the incidence of genital cancer Reduced incidence of some head and neck cancers Potential to stop the cervical cancer screening programme Greater impact in developing countries where there is no cervical screening HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

Disadvantages of introducing the vaccine Cost Only covers 70 – 75% of cervical cancers ?Increased promiscuity Ethical issues of vaccination of teenage girls Delivery to young girls – counselling issues Decreased uptake of smears in screening programme Future role of colposcopy services Long term efficacy Side effects Bad publicity HPV types in cervical cancer This graph shows the cumulative percentages of cervical cancer cases attributed to the most frequent HPV genotypes. In Europe and North America, types 16 and 18 together account for 71.5 per cent of all cervical cancer cases.1 The distribution of HPV types varies within countries and between regions. However, HPV 16 and HPV 18 are the first and second most common types in all regions, with some variation in their distribution. Reference: 1. Muñoz N et al. Int J Cancer 2004; 111: 278–85.

IMPACT OF VACCINE AND DURATION OF PROTECTION 5 4 10 year protection & no screening 3 MORTALITY FROM CERVICAL CANCER DEATHS (PER 100,000 PER YEAR) Screening & no vaccination 2 10 year protection & screening Lifelong & no screening 1 Lifelong protection & screening 10 20 30 40 50 TIME SINCE START OF VACCINATION PROGRAM

Thank You