THE IMPLICATIONS OF HPV VACCINATIONS FOR COLPOSCOPY

hpv The implications of HPV vaccinations for colposcopy

HPV Vaccination Programme
In the UK, HPV vaccination of females aged 12 to 13 years started in September 2008.  A catch up campaign to target girls up to 18 years ran over the subsequent 2-3 years to extend the immunised cohort.  The bivalent HPV16/18 was used initially across the UK. The uptake rates for the HPV vaccine in the UK have been high: 90% of girls eligible for the vaccine in 2010/11 received all three doses.  The vaccine delivered in the school based programme changed to the quadrivalent vaccine in 2013 following the tendering process.  In 2014, the Department of Health, having considered evidence on the antibody response, announced that the vaccine schedule would change from three to two doses from September 2014. 
As girls who received the HPV immunization as part of school based programs, in which the coverage rates are very high, enter the UK cervical screening programs, further data on the impact of the immunization will emerge. The HPA and HPS are responsible for monitoring the uptake and safety of the vaccine and the impact of the programme on cervical screening and cervical disease.

Cervical Screening
In Scotland and Wales, immunised women started being invited to attend for cervical screening in late 2010 as the first invitation to screening starts at age 20 years.  In England and Northern Ireland, screening starts at age 25 and the immunised cohort will start attending for cervical screening later in 2015.
Cervical screening will remain an essential component of the programme both for unimmunised women and for all women who remain at risk from non-vaccine HPV types.  The performance of cervical cytology in terms of positive predictive value (PPV) for CIN is likely to reduce as a result of the falling prevalence of (CIN) and if cytology remains the primary screen, in maintaining skills and pattern recognition with the predicted fall in abnormalities.  Due to lower take rates in the HPV vaccine catch-up programme and also uptake of cervical screening of the youngest age group, the impact is to predicted to become evident in 2015 with a noticeable decline from 2020-2025.

Colposcopy
Colposcopy is used to identify CIN and target such lesions for biopsy and treatment.  It is more sensitive than cytology in identifying high grade CIN but less specific and the colposcopist’s opinion is significantly influenced by knowledge of the referral cytology. Recent evidence has suggested that colposcopic features which are characteristic of high grade CIN are significantly associated with the presence of HPV 16. If the colposcopic features regarded as high grade CIN, actually reflect HPV 16 infection, this could have a significant impact on the performance of colposcopy in the HPV immunised cohort.  Further work from the Netherlands and in immunised women in Scotland, have indicated that the presence of HPV16 does not affect the colposcopic opinion using conventional colposcopy and the effect HPV16 has on the definition of clinical features is dependent on the final histology results.
Emerging evidence of impact on cervical screening and disease prevention.
The impact of vaccination in the UK with high levels of uptake are predicted to result in a 10% decrease in abnormal cytology, 50% decrease in high grade CIN and 70% reduction in cervical cancer.
Data from Australia where the quadrivalent vaccine was introduced in April 2007 from women aged 13-26 years, has already demonstrated a dramatic decline in the proportion of young Australian women with genital warts in the post-vaccination period. The largest decline was of 92.6% (from 11.5% in 2007 to 0.85% in 2011) in women under 21 years (p<0.001). In this same age category, no women who reported prior vaccination were found to have genital warts in 2011. A decline in genital warts was also found in women aged 21-30. The proportion of women diagnosed with genital warts in this age category fell by 72.6% from 11.3% in 2007 to 3.1% in 2011 (p<0.001). No significant trend in the proportion of women diagnosed with genital warts was seen in women over the age of 30 years.   The proportion of men under age 21 being diagnosed with genital warts also significantly decreased by 81.8% from 12.2% to 2.2% in 2011 (p<0.001)  (although they were not a part of the free HPV vaccine programme at that time), suggesting herd immunity.
Data on the early effect of the HPV vaccination on cervical abnormalities from Victoria, Australia has already indicated a significant decrease in high grade cervical abnormalities in girls under the age of 18 years following the introduction of the HPV vaccine. There was no significant decrease in the incidence low grade cervical abnormalities in this same age category or in women aged 18-20 years. No significant decrease in high grade cervical abnormalities was detected in women aged over 21 years, who would have received the vaccine in the catch up programme
.
Evidence is now emerging from the UK on the performance of cytology and colposcopy in vaccinated women.  This indicates that in younger women who have received the vaccine, there is a significant reduction in low and high grade cytology and histology  compared with unvaccinated women.

Worldwide
In 2011, over 28 countries worldwide had implemented either HPV vaccine as part of their national immunization programs. Donations had also enabled over 17 developing countries to implement the vaccine at a sub-national level. In 2013, the GAVI Alliance announced that it had secured a deal to provide a sustainable supply of HPV vaccines to developing countries. By 2020, GAVI hopes to have vaccinated over 30 million girls in more than 40 developing countries.

BSCCP
As a society that aims to promote the highest standards of care in colposcopy, we need to continue to evaluate the evidence from the HPV immunisation programme and cervical screening to predict how it may impact on:
1. Manpower issues for number of colposcopists
2. Training of colposcopists
3. Performance of colposcopy and delivery of care
4. Information for colposcopists
5. Information for women
The remit of the sub-group needs to be ongoing with this evaluation and the issues identified reviewed at the CTC and IT committees.

References

1. Information Services Division. HPV Immunisation Uptake Rates: School Year 2011/12. 25 September 2012; Available at: http://www.isdscotland.org/Health-Topics/Child-Health/Publications/2012-09-25/2012-09-25-HPV-Uptake-Report.pdf?85877627135.
2. https://www.gov.uk/government/publications/hpv-vaccine-uptake-1-september-2012-to-31-may-2013
3. https://www.cas.dh.gov.uk/ViewandAcknowledgment/ViewAlert.aspx?AlertID=101694
4. Jeronimo J, Massad S, Schiffman M. Visual appearance of the uterine cervix: correlation with human papillomavirus detection and type. Am J Obstet Gynecol 2007; 197:47.e1-47.e8.
5. Louwers JA.  Kocken M.  van der Bijl JC.  Berkhof J.  Snijders PJ.  Meijer CJ.  Verheijen RH. Colposcopic characteristics of high-risk human papillomavirus-related cervical lesions. Journal of Lower Genital Tract Disease 2010; 14(1):49-55.
6. Zaal A, Louwers JA, Berkhof J, et al. Agreement between colposcopic impression and histological diagnosis among human papillomavirus type 16-positive women: a clinical trial using dynamic spectral imaging colposcopy. BJOG an International Journal of Obstetrics and Gynaecology.  119(5),537-544 (2012).
7. Munro A, Cruickshank M, Cotton S et al. The Impact of HPV Genotypes on Colposcopic Features in Women Offered HPV Immunisation. BSCCP Annual Scientific Meeting Glasgow 2013. https://www.bsccp.org.uk/assets/file/uploads/resources/BSCCP_Abstracts_2013.pdf.
8. Ali H, Donovan B, Wand H, et al. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ. (2013)

9. Brotherton JM, Fridman M, May CL, Chappell G, Saville AM and Gertig D. Early effect of HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 2011:377;2085.

10. Pollock KGJ, Kavanagh K, Potts A,  Love J, Cuschieri L, Cubie H, Robertson C, Cruickshank M, Palmer T, Robertson C and  Donaghy M. Reduction of low and high grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland. BJC 2014; 1–7 | doi: 10.1038/bjc.2014.479.

11. GAVI Alliance. Millions of girls in developing countries to be protected against cervical cancer thanks to new HPV vaccine deals. 2013; Available at: http://www.gavialliance.org/library/news/press-releases/2013/hpv-price-announcement/#