Diversity of human papillomavirus in the anal canal of men: the HIM Study

Abstract

Human papillomavirus (HPV) infections are associated with development of anogenital lesions in men. There are no reports describing the distribution of non-alpha HPV types in the anal canal of a sexually diverse men group. The HIM (HPV in Men) Study is a multicenter study of the natural history of HPV infection in Brazil, Mexico and USA. At baseline, 12% of anal canal specimens PCR HPV-positive were not typed by the Roche Linear Array and were considered unclassified. Our goal was characterizing HPVs among these unclassified specimens at baseline and assess associations with participant socio-demographic and behavioral characteristics. Unclassified HPVs were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. Further analysis was conducted using FAP primers. Of men with unclassified HPV at the anal canal, most (89.1%) were men who have sex with women (MSW). Readable sequences were produced for 62.8% of unclassified specimens, of which 75.2% were characterized HPV types. A total of 18, 26, and 3 different α-, β- and γ-HPV types were detected, respectively. Compared to older men (45-70 years), α-HPVs were more commonly detected among young men (18-30 years) whereas β-HPVs were more frequent among mid-adult men (31-44 years). β-HPVs were more common among heterosexual men (85.0%) than non-heterosexual men. β2-HPV types composed all β-HPVs detected among non-heterosexual men. The high prevalence of β-HPV in the anal canal of men who do not report receptive anal sex is suggestive of other forms of transmission that do not involve penile-anal intercourse.

Diversity of beta-papillomavirus at anogenital and oral anatomic sites of men: The HIM Study

“…Nevertheless, these results are consistent with our prior findings using a PCR-sequencing method 17 . Higher β-HPV prevalence was observed at the anal canal among middle-aged adults (31–44 years) and older men (>45 years) compared to younger men (18–30 years), whereas no age associations were observed for the external genital skin.…”

“…Nevertheless, these findings contrast with the 40% of β-HPV prevalence observed in male genital skin specimens using a PCR-sequencing protocol 16,32 . A similar prevalence was observed regarding β-HPV detection at the anal canal of HIM participants (54.3% by Luminex versus 31.6% with PCR-sequencing) 17 . Therefore, recently most studies take advantage of the higher sensitivity inherent of the Luminex technology for cutaneous HPV DNA detection (Gheit et al 2007; Donà et al 2015; Torres et al 2015).…”

“…We previously reported the high prevalence of β- and γ-HPVs in the anogenital skin of HIM study participants presumably α-HPV negative by means of not hybridizing to any type-specific probe using the Linear Array methodology and thus categorized as unclassified HPV 16,17,20 . We now widen our analysis to assess β-HPV prevalence at the genital and anal canal of men at the same study visit independent of α-HPV status using a methodology that allows simultaneous detection of 43 β-HPV genotypes 24 .…”

Beta Human Papillomavirus and Associated Diseases

“…Indeed, the recently reported high prevalence of β-HPVs in fingernail samples [43] supports the likelihood of fingers serving as a source of transmission of cutaneous HPVs among distant anatomical sites. Nevertheless, one may not discard that these findings might solely reflect the deposition of virions shed from other anatomic sites [20, 32]. Still, a recent study conducted among heterosexual couples examining anogenital β-HPVs concordance and transmission, suggested that these infections may, at least in part, be sexually transmitted [21].…”

“…Within participants of a multinational study focused on the natural history of HPV infection in men (HIM study) [28], DNA from multiple β-HPVs were detected in the male genitals, anal canal and oral samples [29-32]. Furthermore, among these men, any β-HPVs were more prevalent in the genital skin (81.6%) compared to the forearm skin (64.4%) and EBH (60.9%) [33].…”