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Abstract
Objectives In 2008, a national human papillomavirus (HPV) vaccination programme for females was introduced in England using the bivalent vaccine (HPV16 and 18 only). In 2012, the programme changed to offer the quadrivalent vaccine that includes protection against the two HPV types that cause the majority of anogenital warts (AGW; HPV6 and 11). We present data reporting AGW diagnoses in sexual health clinics (SHCs) in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine.
Methods Using data from all SHCs across England, we performed ecological analyses to consider rates of AGW diagnoses by age, gender and sexual orientation. We tested for trends over time of diagnoses of AGW in young females, heterosexual males, and men who have sex with men (MSM) between the ages of 15 and 24 years during both bivalent (2009 to 2013) and quadrivalent (2014 to 2017) vaccine time periods using Poisson regression.
Results Between 2014 and 2017, there was strong evidence for a decreasing trend in the rate of AGW diagnoses at SHC among females aged 15–17 years from 257.5 to 45.7 per 100 000 population (82.3% decline) and same aged heterosexual males from 59.1 to 19.1 per 100 000 population (67.7% decline). The reductions in the incidence of AGW diagnoses in MSM aged 15–17 years were less clear (decreased by 13.6% between 2014 and 2017, from 129.9 to 112.2 per 100 000 population).
Conclusions The moderate, unexpected declines in AGW seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.
- HPV
- vaccination
- anogenital warts
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Introduction
A national human papillomavirus (HPV) vaccination programme was introduced in the UK in September 2008, initially offering the bivalent HPV vaccine that has high efficacy against the two main HPV types that cause cervical cancer, HPV types 16 and 18.1 Vaccination is offered annually to females aged 12–13 years (those who turn 13 on or after first September, and are therefore due to be in school year 8) and females remain eligible for vaccination up to 18 years of age if they are not vaccinated when first offered. In addition, a catch-up campaign ran in the early years to offer vaccination to all females up to 18 years for the first 2 years of the programme. Vaccination has been primarily delivered in schools. Coverage for the vaccination programme has been high, with figures showing over 85% completion of the full HPV vaccination course in routine cohorts over the last 5 years.2 In 2012, the programme changed to offer the quadrivalent vaccine that has high efficacy against HPV16 and 18 and, additionally, has high efficacy against the two HPV types that cause approximately 90% of anogenital warts (AGWs), HPV types 6 and 11.3 4
Additionally, a targeted HPV vaccination pilot programme for men who have sex with men (MSM) ran from June 2016 to end March 2018 in 42 specialist sexual health clinics (SHCs) and HIV clinics across England. The experience of this pilot supported the decision to proceed to a phased national rollout of targeted HPV vaccination for MSM attending SHC and HIV clinics, from April 2018.5
Prior to 2008, cases of AGW diagnosed in SHC, which include genitourinary medicine (GUM) services and integrated GUM/sexual and reproductive health (SRH) services, had been increasing since the early 1970s.6 7 However, reductions in AGW diagnoses were initially reported in young females from 2009.8 More recently, we have reported data from England to end 2014 showing unexpected, modest declines in AGW diagnoses at SHC since the introduction of HPV vaccination. These declines were associated with coverage levels of the bivalent vaccine and suggested a potential cross-protective effect of the bivalent vaccine against AGW.8–10
Marked falls in AGW have been reported from multisite studies in other countries with high coverage of the quadrivalent vaccine.11–13 Here, we present data reporting AGW diagnoses in SHC in England to the end of 2017, including diagnoses among birth cohorts offered the quadrivalent vaccine. England has a comprehensive national surveillance system of all STI diagnoses across all SHCs. These results add to the existing evidence base on evaluation of the impact of national HPV vaccination, within a unique setting relating to vaccination uptake and sexual behaviours as compared with other countries.
Methods
Data collection
Data were obtained from the GUMCAD STI Surveillance System (hereafter referred to as GUMCAD).14 GUMCAD is a national, mandatory surveillance system. Since 2008, GUMCAD has collected patient-level records of all attendances, tests and diagnoses at all SHCs (GUM and integrated GUM/SRH services) in England. Prior to 2008, clinics reported aggregate data. These surveillance data are collected by SHC and submitted to Public Health England (PHE) on a quarterly basis.15 Since 2012, GUMCAD has also included returns from non-specialist clinics such as SRH and young people’s services. History of attendances, tests and diagnoses by the same individual can be tracked within data from each clinic, but not between clinics.
Information on individual vaccination status was not available. Vaccination coverage was therefore estimated using annual PHE national HPV vaccination programme reports, which are available for each school year routine cohort, as well as for past catch-up cohorts.2 16 Bivalent and quadrivalent vaccination coverage was assigned by single year of age and calendar year based on vaccination cohorts. Because females of a given single year of age could have a date of birth spanning a 24-month period, and could therefore fall within more than one vaccination cohort, vaccination coverage was estimated as a composite for each single year of age and calendar year.
Data analysis
Data for attendances between January 2009 and December 2017 were extracted from GUMCAD. Data from non-specialist clinics was excluded from the analysis, as these have only been reported since 2012 and represent only 3.4% of AGW diagnoses in subjects 15–24 years old. We calculated the number of diagnoses of first episodes of AGW among subjects 15–24 years old. Diagnoses of recurrent AGW were excluded. The data were stratified by age groups (based on age at attendance date) and gender. GUMCAD records sexual orientation as heterosexual, homosexual or bisexual. Males were stratified by sexual orientation as follows: heterosexuals and MSM, the latter defined as any man who had reported being either homosexual or bisexual on at least one clinic attendance (since disaggregate reporting began).
The incidence of AGW diagnoses per 100 000 population was calculated using published midyear population estimates by age and sex for England, with the 2016 population estimates taken as a proxy for 2017 as 2017 data were not yet available at time of analysis.17 For MSM, the population estimate was calculated as 2.9% of the total male population based on data published in the Natsal-3 study of sexual attitudes and lifestyles in the UK on the proportion of males 16–24 years old reporting at least one male sexual partner in the past 5 years.18 The remaining 97.4% of the male population was used as the population denominator for heterosexual males. In addition, we conducted sensitivity analyses of our findings to calculate rates of AGW by age group, gender and sexual orientation using total numbers of attendances at SHC for each of these groups as the denominator.
Percent declines in the rates of AGW diagnoses were calculated during two time periods: between 2009 and 2013, during which all females included in this analysis would have been offered the bivalent vaccine, and between 2014 and 2017, during which most females would have been offered the quadrivalent vaccine. Poisson regression was used to test for trends in diagnoses of first episode AGW within each time period for each population and age group. Stata V.13 was used for all data analysis.
Results
Females
Between 2014 and 2017, there were substantial declines in the incidence of AGW diagnoses in SHC among females aged 15–17 years, from 257.5 per 100 000 population in 2014 to 45.7 per 100 000 population in 2017 (82.3% decline, p value for trend <0.001; table 1). Declines of 24.6% (from 841.5 to 634.2 per 100 000 population) and 19.7% (from 583.8 to 468.6 per 100 000 population) were seen during this same time period in females aged 18–20 and 21–24 years, respectively (p value for trend <0.001 for both). The largest decline between 2014 and 2017 was observed in 15-year-old females. The incidence rate of AGW diagnoses decreased by 92.0% in this group, from 75.9 in 2014 to 6.1 in 2017 per 100 000 population (p value for trend <0.001). Large declines were also seen in 16 and 17 years old females, with the incidence of AGW diagnoses decreasing by 91.4% and 76.6%, respectively (p value for trend <0.001).
Rate of AGW diagnoses and declines in SHC in England over 2009–2013 and 2014–2017 time periods
All females aged 15 and 16 years in 2017 would have been offered the quadrivalent vaccine when aged 12–13 years as part of the national programme, with approximately 85% having received a full course. Additionally, 57.5% and 14.4% of females aged 17 and 18 years in 2017, respectively, would have also received the quadrivalent vaccine when aged 12–13 years. Females 19 years and over in 2017 would have been offered the bivalent vaccine as part of the national programme (figure 1).
(A) Rate of anogenital warts (AGW) diagnoses and female human papillomavirus (HPV) vaccination coverage in England from 2009 to 2017 in subjects 15–17 years old. (B) Rate of AGW diagnoses and female HPV vaccination coverage in England from 2009 to 2017 in subjects 18–20 years old. (C) Rate of AGW diagnoses and female HPV vaccination coverage in England from 2009 to 2017 in subjects 21–24 years old.
There were also moderate declines in the incidence of AGW diagnoses in SHC between 2009 and 2013 among young females who would have received the bivalent vaccine (table 1). A trend was seen in 15–17 years old and 18–20 years old females within this time period, with the incidence of AGW diagnoses decreasing by 36.9% and 11.9%, respectively (p value for trend <0.001).
Heterosexual males
Between 2014 and 2017, declines in the incidence of AGW diagnoses were also seen among 15–17 years old heterosexual males (table 1). The incidence of AGW diagnoses in 15–17 years old heterosexual males was 67.7% lower in 2017 than 2014 (from 59.1 to 19.1 per 100 000 population) and 32.2% lower (from 516.7 to 350.3 per 100 000 population) and 22.1% lower (from 711.2 to 553.9 per 100 000 population) in heterosexual males aged 18–20 and 21–24 years, respectively. Strong evidence for trends were detected in all three age groups (p value for trend<0.001). The greatest trends in reductions of AGW diagnoses between 2014 and 2017 were observed in 15, 16, 17 and 18 years old heterosexual males(52.9%, 71.6%, 67.5% and 42.1%, respectively). There was evidence of reductions in the rate of AGW diagnoses in heterosexual males of all ages up to 24 years in the same time period, though as with same aged females declines were less substantial than in younger ages (figure 1).
Between 2009 and 2013, there were reductions in the incidence of AGW diagnoses in 15–17 years old males (5.8%), though unlike females the Poisson regression analysis showed no clear evidence for a trend (p value for trend 0.162) in this age group. Conversely, there was evidence for an increasing trend in the incidence of AGW diagnoses between 2009 and 2013 in both older age groups (p value for trend <0.001 and 0.004, respectively) (table 1).
Men who have sex with men
The crude incidence of AGW diagnoses in MSM aged 15–17 years decreased by 13.6%, from 129.9 in 2014 to 112.2 in 2017 per 100 000 population. The rate of AGW also decreased by 11.5% (from 1138.7 to 1007.7 per 100 000 population) and 6.6% (from 1842.0 to 1720.8 per 100 000 population) over the same time period for MSM 18–20 years old and 21–24 years old, respectively (figure 1). However, results from the Poisson regression analysis showed no clear evidence for decreasing trends in all three age groups (p value for trend 0.219, 0.193 and 0.232, respectively). There was, however, strong evidence for the decreasing trend seen from 2014 to 2017, 79.1% (from 53.6 to 11.2 per 100 000 population), in 15-year-old MSM (p value for trend 0.043).
In the earlier time period, between 2009 and 2013, increases in the incidence of AGW diagnoses were observed in MSM across all age groups (6.8%, 19.8% and 24.6% increases for males 15–17, 18–20 and 21–24 years old, respectively), though evidence for this increasing trend was only found for MSM 18–20 and 21–24 years old (p value for trend 0.847, <0.001 and <0.001 for MSM 15–17, 18–20 and 21–24 years old, respectively) (table 1).
Discussion
These ecological analyses demonstrate that the incidence of AGW diagnoses at SHC in England has reduced dramatically in young people since 2009, following a steady increase from the 1970s to 2008. Declines from 2009 to 2013 pre-date any impact of the use of the quadrivalent vaccine in the national programme, and these have been discussed elsewhere.8–10 Far greater declines have been seen from 2014 to 2017, particularly in young females who would have been offered the quadrivalent vaccine as part of the national female HPV vaccination programme. The reductions by age group and by estimated HPV vaccination coverage among females during the quadrivalent vaccine period strongly suggest that these declines are associated with the national HPV vaccination programme. Large declines have also been seen among young heterosexual males, which may suggest evidence of herd protection. Small declines have also been observed in MSM.
The most pronounced reductions between 2014 and 2017, over 90%, were observed in young females aged 15 and 16 years, the only groups included in this analysis who would have exclusively received the quadrivalent vaccine at age 12 or 13 years as part of the national programme. All other single age cohorts included either a combination of females who would have received the bivalent and quadrivalent vaccine, or only females who would have received the bivalent vaccine. However, there was also evidence of marked decreases in 17 and 18 years old females, most of whom would have also received the quadrivalent vaccine when aged 12 or 13 years. While declines were most salient in the youngest ages and 15-17 years age group, decreases in the rates of AGW diagnoses in females were also observed across all older ages and age groups.
Similar patterns of decreases in AGW diagnoses were observed in heterosexual males. These ecological observations suggest that the high coverage female-only HPV vaccination programme is affording substantial herd protection to young males. There is also some evidence for herd protection affecting older individuals, in particular older heterosexual males. A slightly older age distribution of protection can be observed in heterosexual males as compared with females, most likely explained by known age differences in sexual partnerships.19 Similar patterns have been observed in age distributions for other STI diagnoses.20
In Australia, there was evidence of a reduction in AGW for MSM.12 In our analysis, small declines were also observed in MSM in all three age groups between 2014 and 2017, in contrast to the increases seen between 2009 and 2013 in this population, though there was no clear evidence for a decreasing trend when we performed a Poisson regression analysis. However, there was strong evidence of a decreasing trend when restricting to 15-year-old MSM, though absolute numbers of AGW diagnoses within this group were low and these results are still premature. Notably, similar declines in the incidence of other STIs have not been observed for MSM.21 Declines in the youngest MSM may be due to more bisexual sexual behaviours in young males, which may be affording young MSM with some degree of herd protection.18 Additionally, targeted vaccination of MSM is offered opportunistically at SHC and MSM may have been previously exposed to HPV6 or 11 prior to vaccination. Therefore, declines in AGW among MSM as a result of vaccination are not expected to be as dramatic as declines seen in females and may take longer to emerge.22 For completeness, we have compared diagnoses of AGW among MSM attending clinics participating in the HPV vaccination pilot with AGW diagnoses among MSM attending other SHC. As expected, given the relatively short duration since the start of the pilot, there was no evidence of stronger declines in pilot clinics versus non-pilot clinics. Within the timeframe of this analysis, the majority of MSM who would have been eligible for HPV vaccination as part of the pilot would be unvaccinated or have only received partial vaccination. Therefore, any declines in AGW seen in young MSM are not likely to be attributable to the targeted HPV vaccination pilot for MSM. Analyses to evaluate the impact of targeted HPV MSM vaccination on AGW will be considered in the future.
Surveillance data from other countries implementing national vaccination programmes have shown significant declines in AGW in both young females and heterosexual males following their introduction, both in the form of herd protection for males, as well as via direct protection through a gender-neutral programme.11 13 23–25 In contrast with similar analyses conducted in other countries with high-coverage national HPV vaccination programmes, this analysis benefits from national surveillance data which collects all diagnoses of AGW among all sexual health attendances in England. A major limitation of this analysis is the inability to link AGW diagnoses to individual vaccination status. Vaccination status in England for the female national HPV vaccination programme is not collected via GUMCAD, precluding the ability to accurately estimate vaccine effectiveness. In previous analyses, we have quantified the association between vaccination coverage and AGW diagnoses.8 9 This current analysis predominantly includes females from routine vaccination cohorts. As vaccination coverage for routine cohorts has been relatively stable over time (>80%), quantifying the association between vaccination coverage and AGW diagnoses provides little additional information to analyses comparing trends in diagnoses over time. A further limitation is that changes in the number of patients attending SHC could affect trends in AGW, particularly if patients were attending elsewhere for treatment of AGW (eg. general practitioners). Previous data have shown that the vast majority of AGW are seen and diagnosed in SHC.26 Additionally, the number of attendances at SHC has been shown to be relatively stable over time.27 However, to consider this further, we conducted sensitivity analyses of our findings to recalculate rates of AGW diagnoses by age group, gender and sexual orientation using total numbers of attendances at SHC as the denominator, rather than the total population. Results from the sensitivity analysis showed very similar results for declines of AGW during the quadrivalent period.
The marked declines in AGW diagnoses observed in this analysis are likely to have an impact on the costs of SHC and general practice care. Previous work has shown that the average cost of care per episode of AGW in England in 2008 was £113.26 28 If compared with an assumed steady continuation of the incidence of AGW as in 2009, there has been a total reduction of 14 817 diagnoses of AGW in England between 2014 and 2017, which amounts to a £1 674 321 cost saving over this time period. The reductions in AGW seen are consistent with the reductions predicted by mathematical models and therefore provide positive validation of this aspect of the cost-effectiveness analysis that have informed the national programme decisions.
Conclusions
The moderate, unexpected declines in AGW that we have seen since the introduction of a high-coverage HPV vaccination programme using the bivalent vaccine are being followed, as expected, by much larger declines among females offered the quadrivalent vaccine and same-aged heterosexual males. Surveillance plans are in place to continue to monitor AGW diagnoses in years to come to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.
Key messages
Substantial declines in the incidence of anogenital warts (AGWs) in sexual health clinics have been seen in young females offered the quadrivalent human papillomavirus (HPV) vaccine and same-aged heterosexual malessince the introduction of the HPV vaccination programme in England.
Reductions in the incidence of AGW were also seen in young MSM, though these results were less clear.
Surveillance plans are in place to monitor AGW diagnoses to evaluate the impact of both female and targeted MSM HPV vaccination on early disease outcomes.
Acknowledgments
We thank the GUMCAD STI Surveillance System team and all clinics that report data to GUMCAD.
References
Footnotes
Handling editor Jackie A Cassell
Contributors This work was initiated and designed by MC, DM and KS. HM was responsible for the data collection and management. MC conducted the statistical analysis and wrote the first draft of the manuscript. All authors contributed to and approved the final draft.
Funding This work was supported by Public Health England.
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Unpublished data are available from GUMCAD by request.