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  • In men, human papillomavirus (HPV) can cause cancer of the anus, tongue, throat and penis
  • Gay and bisexual men who used HIV pre-exposure prophylaxis (PrEP) had very high rates of HPV
  • Researchers encourage HPV screening and vaccination among men who use PrEP

Human papillomavirus (HPV) is a common sexually transmitted infection. Some strains (called genotypes) of HPV can cause anal, oral (head and neck) and penile cancer in men.

About six years ago, researchers in Canada and France published the results of a clinical trial of pre-exposure prophylaxis (PrEP) for HIV. This trial was called Ipergay and enrolled gay and bisexual men, some of whom received tenofovir DF and others who received placebo.

A sub-study of Ipergay focused on HPV and related issues in 162 men who had not been vaccinated against HPV. Over the course of two years, researchers found that there was a good chance that genotypes of HPV that are associated with cancer would be found in the men, particularly in the anus.

Based on their findings, the researchers recommended offering screening for anal cancer and HPV vaccination in gay and bisexual men who use PrEP.

Study details

At the start of the sub-study, participants completed questionnaires and gave blood and samples for HPV testing. To obtain HPV samples, swabs of the anus and penis were used. For the mouth and throat, a solution was gargled and collected. Most participants were in their 30s.

All participants underwent proctology examinations.

Results of assessments for abnormal cells in the anus were graded as follows:

  • not enough cells for analysis
  • normal
  • atypical squamous cells of undetermined significance (ASC-US)
  • low-grade squamous intra-epithelial lesion (LSIL)
  • high-grade squamous intra-epithelial lesion (HSIL)
  • atypical squamous cells that cannot exclude HSIL (ASC-H)

Cells that have been graded LSIL and HSIL are the most concerning in the short term, as they can further transform and become highly abnormal and pre-cancerous.


At the start of the study, HPV was found in 93% of men in one of the anatomical sites previously mentioned.

Overall, HPV was more often detected from the anus than the other sites.

Over the course of the study, researchers found the following changes:

  • anus – 79% of the men acquired at least one new high-risk genotype
  • penis – 27% of the men acquired at least one new high-risk genotype
  • mouth – 20% of the men acquired at least one new high-risk genotype

The risk of becoming infected with a new high-risk genotype was similar whether participants received tenofovir DF or placebo.

Anal examinations

Assessments for abnormal cells in the anus found the following test results at the start of the study:

  • normal – 32%
  • ASC-US – 23%
  • LSIL – 40%
  • HSIL – 5%
  • ASC-H – 1%

By the end of the study, the distribution of test results was as follows:

  • normal – 13%
  • ASC-US – 21%
  • LSIL – 51%
  • HSIL – 10%
  • ASC-H – 1%

Thus, there was a trend toward a higher proportion of abnormal cells in the anus over time. None of the participants developed anal cancer during the study.

Additional findings and implications

The researchers noted that in previous studies HIV-positive gay and bisexual men had high levels of HPV infection, in part because their immune systems were unable to contain HPV.

In the present sub-study, the researchers found similarly high levels of HPV infection among HIV-negative gay and bisexual men. The study was small and not designed to assess cancer risk from HPV infection. However, the researchers stated that “PrEP-using men who have sex with men should definitely be considered a high-risk population regarding anal HPV infection and the associated risk of complications.”

According to the researchers, assessment of the swabs from the penis also found high levels of HPV—“much higher than previously reported in [gay and bisexual men] without HIV.”

In contrast to the anus and penis, analysis of fluid from the mouth found “relatively low” levels of HPV. These low levels were similar to those reported in other studies with HIV-negative gay and bisexual men.

Note that Ipergay preferentially recruited men who had condomless anal intercourse in the recent past. This focus on recruiting men who practised condomless anal intercourse may have increased the likelihood of detecting HPV in their anus.

HPV vaccination

In Canada and other high-income countries, a vaccine called Gardasil 9 is approved. This vaccine greatly reduces the risk of infection with certain genotypes of HPV and problems caused by them:

  • HPV – 6 and 9; these cause anogenital warts
  • HPV – 16, 18, 31, 33, 45, 52 and 58; these are associated with an increased risk of cancer in affected body parts

The researchers found that some high-risk HPV genotypes (16, 18, 31 and 52) were increasingly common in the anuses of the men over the course of the study. They stated that this finding suggests that the men were susceptible to infection by these genotypes.

As mentioned previously, “high-risk” genotype is the term used by researchers for strains of HPV that are associated with an increased risk for cancer. Interestingly, the proportion of men with abnormal anal pap test results rose from 5% at the start of the study to 15% at the end. Thus, the men were likely vulnerable to HPV genotypes that cause abnormal cell development and growth in their anuses. Over time, this could increase their risk for anal pre-cancer and cancer.

Taking all of their findings into account, the researchers suggested that vaccination against HPV with Gardasil 9 would be beneficial in gay and bisexual PrEP users. Although there are three approved HPV vaccines, Gardasil 9 provides the broadest coverage against the most HPV genotypes. The researchers also recommended “similar cancer screening and vaccination strategies” in men who have sex with men, regardless of whether they are HIV negative or positive.

—Sean R. Hosein


Pre-exposure prophylaxis (PrEP) resources and tools

Injectable cabotegravir highly successful at preventing HIV infection in women – CATIE News

Health Canada licenses HIV self-testing – CATIE News

Transgender people found to have effective levels of HIV prevention drug – CATIE News

Long-acting injectable drug prevents HIV – CATIE News

HPV, anal dysplasia and anal cancer – CATIE factsheet

Addressing HPV-related cancer risk among men who have sex with men (MSM): A guide for health care providers – Sex Information and Education Council of Canada (SIECCAN)


Cotte L, Veyer D, Charreau I, et al. Prevalence and incidence of human papillomavirus infection in men having sex with men enrolled in a pre-exposure prophylaxis study: A sub-study of the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales “Intervention Préventive de l’Exposition aux Risques avec et pour les hommes Gays” Trial. Clinical Infectious Diseases. 2021 Jan 23;72(1):41-49.