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Volume 8 No 24; 20 June 2014

Declines in genital warts since start of the HPV immunisation programme

Genital warts (GW) diagnoses in genitourinary medicine (GUM) clinics (collected in the GUM Clinic Activity Dataset (GUMCADv2)) among 15-19 year-old females in 2013 were 6% lower than in 2012 (511 vs 544/100,000). This continues the trend seen since 2008 of declining GW among females eligible for HPV immunisation.

The United Kingdom was the first country to introduce (in September 2008) a national human papillomavirus (HPV) immunisation programme using the bivalent HPV 16/18 vaccine (Cervarix; GlaxoSmithKline). This vaccine was used until September 2012. The programme has attained high coverage, with reported three-dose coverage in the routine cohorts, vaccinated at age 12-13 years, of more than 80% and approximately 40% or greater in the oldest catch-up cohorts, immunised at age 17 years [1-3].

The quadrivalent HPV 6/11/16/18 vaccine (Gardasil; Sanofi Pasteur MSD) which replaced Cervarix in the UK immunisation programme from September 2012 [4] has been shown to be highly effective in preventing GW (mostly caused by low risk HPV types 6 and 11), both in clinical trials and in practice in high-coverage immunisation programmes [5]. However, no impact on GW was anticipated from the use of the bivalent HPV 16/18 vaccine in the immunisation programme in England [6].

A slight but notable decrease in the number of GW diagnoses in GUM clinics among young females was observed in data from 2008 to 2011[7]. Subsequent more detailed ecological analyses, and similar analyses of GW diagnoses in General Practice, found the size and pattern of the declines strongly suggestive of an unexpected, moderately protective effect of HPV 16/18 vaccination against GW [8].

Data to the end of 2013 show a rise in numbers of GW diagnoses (at all ages) in the last 10 years in males, and in females a parallel rise up to 2008 followed by a decline [9]. This overall levelling of GW diagnoses in females in the past 10 years was due to continuation of the declines seen since 2008 among young females. There was a significant decrease of 28% (95% CI 26%-30%) in the number of GW diagnoses at GUM clinics per 100,000 population (using mid-year population denominators) between 2008 and 2013 for females aged 15 to 19 years, and of 9% (95% CI 7%-11%) for females aged 20-24 years. A decrease of 17% (95%CI13%-21%) was seen for 15-19 year old males over the same time period (see figure). The greatest declines were seen among 15, 16 and 17 year old females (43.7%, 37.9%, and 40.9% respectively). Females aged 15-17 years in 2013 would have been aged 9-14 years at the start of the vaccination programme in 2008, and therefore largely eligible for routine HPV vaccination (with reported coverage of >80%). The percentage declines lessen with increasing age, as does the estimated vaccine coverage (and the age at vaccination increases). In females above the age eligible for HPV immunisation, and same aged males, diagnoses rates showed no similar declines (see figure).

The factors that might be contributing to declines in GW in young females have been discussed previously, with analysis of data to end 2011 [8]. This updated analysis of data to the end of 2013 shows greater decreases in GW diagnoses and a strengthening of the association with coverage of the bivalent HPV16/18 immunisation. A post hoc analysis of the PATRICIA (PApilloma TRIal against Cancer In young Adults) trial has shown moderate efficacy for the bivalent HPV16/18 vaccine against persistent infection with a number of low risk HPV types, and estimated efficacy for six-month persistent infection with HPV 6/11 of 34.9% (9.1 to 53.7) [10]. There is some biological plausibility for broad cross protection from the bivalent vaccine [11]. No other sufficient explanations for the pattern and size of the declines in females have come to light. We are conducting a case-control analysis of GW among females eligible for bivalent vaccination to investigate this further. The smaller declines in young males are suggestive of a herd-protective effect from cross-protection against 6/11 in females receiving the bivalent vaccine. However, the other factors that may be contributing to declines in females, including private use of the quadrivalent vaccine, imported herd-protection from quadrivalent vaccine use abroad and herd-protection against a proportion of GW caused by HPV16/18, could if summed explain the declines among males within probable ranges of uncertainty.

Rates of first genital wart diagnosis in females (with error bars showing 95% confidence intervals) and human papillomavirus immunisation coverage in England, by age and year

References

1. http://webarchive.nationalarchives.gov.uk/20130123170526/http://immunisation.dh.gov.uk/annual-hpv-vaccine-coverage-in-england-in-201011-report/.

2. Department of Health. Annual HPV vaccine coverage in England in 2011/12 report. http://webarchive.nationalarchives.gov.uk/20130123170526/http:/immunisation.dh.gov.uk/tag/hpv-vaccine-uptake/.

3. Public Health England. Annual HPV vaccine coverage 2012 to 2013: by PCT and SHA. https://www.gov.uk/government/publications/annual-hpv-vaccine-coverage-2012-to-2013-by-pct-and-sha.

4. HPV immunisation programme: change of vaccine to Gardasil from September 2012. HPR 6(4), December 2012.

5. Ali H, Donovan B, Wand H, Read TR, Regan DG, Grulich AE, Fairley CK, Guy RJ. Genital warts in young Australians five years into national human papillomavirus vaccination programme: national surveillance data. BMJ 2013; 346:f2032.

6. Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus vaccination in the United Kingdom. BMJ 2008; 337:a769.

7. Sexually transmitted infections in England, 2011. HPR 6(22), 1 June 2012.

8. Howell-Jones R, Soldan K, Wetten S, Mesher D, Williams T, Gill ON, Hughes G. Declining genital Warts in young women in England associated with HPV 16/18 vaccination: an ecological study. J Infect Dis. 2013 Nov 1; 208(9):1397-403.

9. Sexually transmitted infections and chlamydia screening in England, 2013. HPR 8(24), Advanced Access report published on 17 June 2014.

10. Szarewski A, Skinner SR, Garland S, et al. Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low risk HPV types (PATRICIA randomised trial): an unexpected observation. J Infect Dis. 2013; 208:13916.

11. Hepburn HM, Seipel M, Schwarz T, Pawlita M, Waterboer T, Kaufmann AM. Ex vivo monitoring of cellular memory responses in young women immunized with either Gardasil or Cervarix four years prior to enrollment, IPV 2009, Malmo [P-13.13].