Genital warts are caused by human papillomavirus (HPV), the commonest viral sexually transmitted infection. Human papillomavirus is highly contagious and may be transmitted through genital, anal, or oral sexual contact. The lifetime risk for acquiring HPV in unvaccinated men is approximately 91% (range, 70%–98%).1
Human papillomavirus DNA and HPV antibody testing are not routinely conducted in boys and men but are confined to research studies.2,3 Although most HPV is subclinical, genital warts that are mainly symptomatic may be a useful indication of incident HPV-6 and HPV-11. Indeed, the monitoring of the diagnoses of warts in sexual health service attendees in Australia provided early evidence of the impact of HPV vaccination within the heterosexual population.4 Although there is evidence that HPV vaccination of girls and women reduces the prevalence of HPV in heterosexual male individual,5,6 the impact of HPV vaccination on HPV among men who have sex with men (MSM), many of whom are at increased risk for anal cancer, is unknown.7 Furthermore, because most countries do not have universal HPV vaccination of boys, understanding the age-related patterns for acquisition of anogenital warts might help with deciding how effective catch-up vaccinations programs could be.
The aim of this study was to examine the age-specific patterns of anal and penile warts among MSM attending a sexual health service in Melbourne, Australia. This information is an important parameter for modeling of HPV transmission and vaccine effectiveness that use warts as a proxy for its effectiveness.
Melbourne Sexual Health Centre (MSHC), a free sexual health service, keeps an electronic medical record of demographics, epidemiologic, and clinical data for all patients attending the service. At each visit, practitioners select at least one diagnosis from a preformatted list that includes anal or genital warts. Warts were diagnosed through physical examination without the use of acetic acid. We extracted data from this record and determined the proportion of all new MSM patients who were diagnosed as having anogenital warts attending MSHC between January 2008 and June 2016. Men attending the clinic before 2008 did not have the site of the wart diagnosis recorded. We included MSM 16 years and older who reported no female partners in the last 12 months and had not received any HPV vaccination. The analysis was stratified into 5 age groups (<21, 21–30, 31–40, 41–50, and >50 years). As a comparator and proxy for sexual behaviors, we also extracted data on urethral and rectal chlamydia. We used men who reported receptive anal sex within the last 12 months and had tested for rectal chlamydia as the denominator to calculate the proportion of men with anal warts or rectal chlamydia. Similarly, men who reported insertive anal sex within the last 12 months and had tested for urethral chlamydia were used as the denominator to calculate the proportion of men with penile warts or urethral chlamydia.
Data were analyzed using STATA version 13 (StataCorp, College Station, TX). Descriptive analyses were conducted for percentages and frequencies of key parameters. The 95% confidence intervals for the sample proportions were calculated using the Agresti-Coull method. This research was approved by the Alfred Hospital Human Ethics Committee (353/16).
There were 15,590 individual MSM who attended MSHC for their first consultation between 2008 and 2016 who fulfilled the inclusion criteria. The median age was 28 years (interquartile range, 24–46 years) and approximately half (51%; n = 7996) were born in Australia. Six percent (n = 945) were men living with HIV. Approximately a quarter (27%; n = 4,276) reported having a regular male partner, and 32% (1210/3771) reported using condoms always with a regular partner during receptive and 33% (1249/3826) during insertive anal intercourse. Approximately half (49%; n = 7699) reported a casual partner in the preceding 3 months, and 54% (3453/6421) reported using condoms always with a casual partner during receptive and 53% (3621/6815) during insertive anal intercourse. A total of 9576 men reported receptive anal sex, 9846 reported insertive anal sex, and 10,762 reported both receptive and insertive anal sex in the preceding 12 months.
Overall, 4.5% (432/9576) of men reporting receptive anal sex had anal warts, 1.5% (143/9846) of men reporting insertive anal sex had penile warts, and 0.1% (14/10762) of men reporting both receptive and insertive anal sex had both anal and penile warts. Figure 1 shows that there were no statistically significant differences for the proportion of men diagnosed as having penile warts according to age groups (Ptrend = 0.72), but there was a significant decline in anal warts (Ptrend < 0.001). Even when we used all MSM in the denominator (i.e., regardless of reports of anal sex), the result did not change: there were no statistically significant differences for the proportion of men diagnosed as having penile warts according to age groups (Ptrend = 0.85), but there was a significant decline in anal warts (Ptrend < 0.001; Supplementary Fig. S1, http://links.lww.com/OLQ/A196). There was no statistically significant change in either urethral (Ptrend = 0.09) or rectal chlamydia positivity (Ptrend = 0.29) by age. We also noticed a significant decrease in the proportion of warts over time for penile warts (2.4% in 2008–2010, 1.3% in 2011–2013, 1.2% in 2014–2016; Ptrend < 0.01) and anal warts (5.3% in 2008–2010, 5.2% in 2011–2013, 3.6% in 2014–2016; Ptrend = 0.01).
We examined the proportion of men presenting with warts by site and age in an unvaccinated MSM population for HPV. We found that anal warts were most common in younger MSM (5.8% for age <21 years) and became less common with age (2.8% for age >50 years) but that penile warts occurred at approximately the same proportion over all age groups (~1.5%). The proportion of warts over time also significantly decreased and may coincide with falling wart diagnoses in men who have sex with women due to herd immunity, but we do not know why this decline is occurring in MSM. Furthermore, our data provide baseline age-specific wart data for MSM in Australia in the context of preexisting female vaccination (since 2007) and more recent male vaccination (since 2013), and this information will allow for the tracking for future trends in warts in MSM.
There are a number of possible explanations for our finding that anal warts declined with increasing age but that penile warts did not. The first is that anal and penile susceptibility to HPV differs according to age. Specifically, anal HPV is acquired more easily in younger MSM and may indicate that the anal epithelium of younger MSM may be more susceptible to HPV infection than older MSM. If immunity from previous exposure was the reason for the decline in anal warts with age, we would expect to see a similar decline in penile warts. The decline in anal warts with increasing age may reflect the relative difficulties in diagnosing anal warts, especially if warts are intrarectal, are smaller in size, or have more subtle appearances compared with penile warts. Other possible explanations include differences in the duration of immunity at the 2 sites, differences in the proportion of HPV-6/11 infections that are symptomatic by age at both sites, or any uncontrolled bias.
Studies have shown that the prevalence of penile HPV DNA does not change with age,8 but the prevalence of anal HPV decreased with age.3 Specifically, in a study of 176 MSM in the HPV in Men Study, the prevalence of any anal HPV types was 60% in men aged 18 to 24 years and decreased to 18% in men older than 45 years.3 Furthermore, in a study of MSM younger than 20 years, the incidence of anal HPV was 4.8 times higher than penile infection, but no similar study was done in older MSM.9
Our study should be read in light of some limitations. The study is a record review from one sexual health center and thus is subject to the biases associated with retrospective reviews and may not be generalizable to all MSM. Melbourne Sexual Health Centre serves approximately 15% of the MSM population in Victoria each year, with a bias toward sexually active MSM compared with the general population of MSM. Men who have sex with men may seek management of warts through their general practitioner. Not all incident HPV-6/11 cases result in men presenting with anogenital warts, and thus, our results are likely to be an underestimate of the true proportion of MSM with anogenital warts. To minimize bias in this study, we included in our analysis only MSM who reported receptive anal sexual exposure for anal warts/chlamydia and only MSM who reported insertive anal sexual exposure for penile warts/urethral chlamydia, to remove the bias that older men were less likely to practice anal sex. Second, we included chlamydia as an alternative to adjusting for numbers of sexual partners and condom use because reporting of these risks may be biased. We show that for chlamydia, there was no change at either site by age, consistent with other studies showing sustained sexually transmitted infection risk in older MSM.10
This study provides baseline data for tracking changes in warts in MSM. As the proportion of MSM who are vaccinated against HPV increases over time, there is an expectation for a change in the age-specific pattern of warts. Our study also provides further evidence that young MSM may be particularly susceptible to anal HPV infection. The implications of this are that any selective HPV vaccine campaign will need to vaccinate very young MSM to attain maximal efficacy at preventing anal cancer. However, given that MSM may not disclose their sexual orientation to health practitioners until after a median of 15 partners,11 this may be too late for them to derive benefit from HPV vaccination. Indeed mathematical models show that large declines in anal cancer will only occur with a childhood vaccination program.12
1. Chesson HW, Dunne EF, Hariri S, et al. The estimated lifetime probability of acquiring human papillomavirus in the United States. Sex Transm Dis 2014; 41:660–664.
2. Blas MM, Brown B, Menacho L, et al. HPV prevalence in multiple anatomical sites among men who have sex with men in Peru. PLoS One 2015; 10:e0139524.
3. Nyitray AG, Carvalho da Silva RJ, Baggio ML, et al. Age-specific prevalence of and risk factors for anal human papillomavirus (HPV) among men who have sex with women and men who have sex with men: The HPV in men (HIM) study. J Infect Dis 2011; 203:49–57.
4. Donovan B, Franklin N, Guy R, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: Analysis of national sentinel surveillance data. Lancet Infect Dis 2011; 11:39–44.
5. Chow EP, Danielewski JA, Fehler G, et al. Human papillomavirus in young women with Chlamydia trachomatis
infection 7 years after the Australian human papillomavirus vaccination programme: A cross-sectional study. Lancet Infect Dis 2015; 15:1314–1323.
6. Machalek DA, Chow EP, Garland SM, et al. Human papillomavirus prevalence in unvaccinated heterosexual men after a national female vaccination program. J Infect Dis 2017; 215:202–208.
7. Grulich AE, Poynten IM, Machalek DA, et al. The epidemiology of anal cancer. Sex Health 2012; 9:504–508.
8. Giuliano AR, Lu B, Nielson CM, et al. Age-specific prevalence, incidence, and duration of human papillomavirus infections in a cohort of 290 US men. J Infect Dis 2008; 198:827–835.
9. Zou H, Tabrizi SN, Grulich AE, et al. Site-specific human papillomavirus infection in adolescent men who have sex with men (HYPER): An observational cohort study. Lancet Infect Dis 2015; 15:65–73.
10. Poynten IM, Grulich AE, Templeton DJ. Sexually transmitted infections in older populations. Curr Opin Infect Dis 2013; 26:80–85.
11. Simatherai D, Bradshaw CS, Fairley CK, et al. What men who have sex with men think about the human papillomavirus vaccine. Sex Transm Infect 2009; 85:148–149.
12. Zhang L, Regan DG, Ong JJ, et al. Targeted human papillomavirus vaccination for young men who have sex with men in Australia yields significant population benefits and is cost-effective. Vaccine 2017; 35:4923–4929.