Human Papillomavirus Vaccination for Men

Advancing Policy and Practice

Peter A Newman; Ashley Lacombe-Duncan

Disclosures

Future Virology. 2014;9(12):1033-1047. 

In This Article

Background

HPV is among the most common sexually transmitted infections (STI) worldwide.[1] In the USA alone, approximately 20 million people are infected with HPV, and an estimated 6.2 million people are newly infected each year.[1] Most HPV infections are asymptomatic and resolve over time; however, several HPV types have been identified as causal agents in genital warts and various cancers.[2,3]

Research on HPV has heretofore focused predominantly on women due to the association of HPV infection with cervical cancer; however, increasing evidence indicates the association between HPV infection and various cancers in men. In the absence of national HPV prevalence data among men in the USA, a systematic review of 40 studies of HPV DNA detection identified a broad range of HPV prevalence from 1.3–72.9% across studies based on multiple anatomic sites and testing methods, with most studies indicating ≥20% HPV prevalence.[3] Prevalence of the high-risk type HPV-16 was estimated at 7.9% among men in the general population and 18.7–48.0% among STD clinic attendees.[3] Other studies have estimated the prevalence of anogenital HPV infection among men in the USA at 15% among heterosexual men, 60% in men who have sex with men (MSM) who are HIV-negative and 95% in HIV-positive MSM.[4–6]

The HIM cohort study among heterosexual men in Brazil, Mexico and the USA, identified overall HPV prevalence of 65.2% based on combined DNA from genital sites (coronal sulcus, glans penis, shaft and scrotum), with HPV-16 (6.5%) the most commonly detected oncogenic form.[7] A systematic review and meta-analysis of 31 studies of genital HPV DNA among men in Europe revealed pooled HPV prevalence of 12.4% among men from the general population and 30.9% from men in high-risk populations, with significantly higher (28.5%) prevalence in studies published after 2000 versus earlier studies (8.8%).[8] HPV-16 was the most prevalent high-risk HPV type in both populations.[8]

Several studies reveal the highest prevalence of genital HPV DNA detection among men in Africa,[9] with the greatest global burden of penile cancer in sub-Saharan Africa.[10] Penile HPV prevalence was estimated at 50% among young HIV-negative men in Kenya based on DNA detection, with variations by anatomical site; high-risk HPV positivity was 39% in the glans/coronal sulcus, 31% in the shaft and 13% in the urethra, with HPV-16 the most common type.[11] High-risk HPV incidence based on DNA detection from penile swabs among heterosexual men aged 15–49 years in Uganda was 32.9/100 person-years for HIV-negative men and 66.5/100 person-years for HIV-positive men, with the highest incidence among younger men, aged 15–24 years.[10]

In the case of oral HPV, a systematic review estimated overall pooled prevalence at 4.5% among healthy individuals, with similar prevalence in men and women.[12] Oral HPV-16 accounted for 28.0% of all oral HPV infections, with greater prevalence in developing versus developed countries.[12] A nationally representative US study of men and women aged 14–69 years indicated overall oral HPV prevalence of 6.9%, with HPV-16 (1.0%) the most prevalent.[13] Men had significantly higher prevalence than women for overall oral HPV infection (10.1 vs 3.6%) and oral HPV-16 (1.6 vs 0.3%).[13] The HIM cohort study identified incidence of 4.4% for oral HPV infection, 1.7% for oral oncogenic HPV infection and 0.6% for HPV-16 infection.[14] Oral HPV prevalence up to 45% has been reported in HIV-positive men.[15] Oncogenic HPV types were identified in oral samples of 8.8% of HIV-negative MSM and 24.8% of MSM living with HIV in a study conducted in The Netherlands.[16]

An estimated 80–90% of anal cancers and 40–50% of penile cancers are attributable to high-risk HPV types.[17–19] HPV-16 is a significant risk factor for the development of anal intraepithelial neoplasias, anal cancer[20] and oropharyngeal cancer.[21] Importantly, while oral HPV-16 infection and oropharyngeal cancer are rare, men are disproportionately affected, with cancer incidence fourfold higher than that observed in women.[22] HPV-16 has now replaced tobacco as the primary cause of oropharyngeal cancers,[23] shifting the epidemiology of these cancers from older, lifetime tobacco users to men aged 25–50 years.

Notably, amidst an overall decline in death rates from cancers and overall decreases in cancer incidence rates among men in the USA, incidence rates have increased for anal and oropharyngeal cancers.[22,24] Available data indicate that anal cancer has increased from 0.5 cases per 100,000 in 1974 to 1.3 cases per 100,000 in 2004.[25] The high prevalence of anal HPV among MSM is associated with 44-times higher incidence of anal cancer, and among HIV-positive MSM approximately 60-times higher incidence of anal cancer, than the general population.[26,27] Overall, oral cancers (including mouth, tongue, tonsil and throat cancer) kill nearly three-times as many people every year in the USA as cervical cancer.[23]

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