Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in the Men Who Have Sex with Men from the OHMAR Study

Abstract

Both mucosal and cutaneous Human Papillomaviruses (HPVs) can be detected in the oral cavity, but investigations regarding the epidemiology of cutaneous HPVs at this site are scarce. We assessed mucosal (alpha) and cutaneous (beta and gamma) HPV infection in oral samples of HIV-infected and uninfected men who have sex with men (MSM). Oral rinse-and-gargles were collected from 310 MSM. Alpha HPVs were detected using the Linear Array, whereas beta and gamma HPVs were detected using multiplex PCR and Luminex technology. An amplicon-based next-generation sequencing (NGS) protocol was applied to a subset of samples collected from 30 HIV-uninfected and 30 HIV-infected MSM. Beta HPVs were significantly more common than alpha types (53.8% vs. 23.9% for HIV-infected subjects, p < 0.0001; 50.3% vs. 17.1% for HIV-uninfected subjects, p < 0.0001). Gamma HPVs were also frequently detected (30.8% and 25.9% in HIV-infected and uninfected MSM, respectively). NGS produced 2,620,725 reads representative of 146 known HPVs (16 alpha-PVs, 53 beta-PVs, 76 gamma-PVs, one unclassified) and eight putative new HPVs, taxonomically assigned to the beta genus. The oral cavity contains a wide spectrum of HPVs, with beta types representing the predominant genus. The prevalence of beta and gamma HPVs is high even in immunorestored HIV-infected individuals. NGS confirmed the abundance of cutaneous HPVs and identified some putative novel beta HPVs. This study confirms that cutaneous HPVs are frequently present at mucosal sites and highlights that their pathological role deserves further investigation since it may not be limited to skin lesions.

Predictors of Oral Infection by Mucosal and Cutaneous Human Papillomaviruses in HIV-Infected and Uninfected Men Who Have Sex with Men of the OHMAR Study

“…Data about the prevalence of oral infection by alpha, beta, and gamma HPVs in the same groups of HIV-infected and uninfected MSM included in the present study have been previously presented and discussed [6]. Briefly, we found that oral HPV prevalence rates in our participants exceed those observed in non-MSM and other populations, possibly because of different demographic characteristics (e.g., age and ethnicity) and sexual behavior.…”

“…Regarding beta and gamma HPVs, the use of a type-specific assay with a wide capacity to detect multiple genotypes certainly may have contributed to the higher prevalence for these HPVs. Moreover, the prevalence rates observed for the three genera at oral level differed from those assessed at anal level, as already discussed [6,16].…”

“…However, studies are increasingly reporting that cutaneous HPVs, mainly of the beta and gamma genera, are abundantly present in the oral cavity. The prevalence varies between 10 and 50% for beta HPVs [2][3][4][5][6], and is in the range of 3-30% for gamma types [3,4,6]. Despite the fact that ultimate data on the role of cutaneous HPVs in head and neck cancer (HNC) etiology are still lacking, oral infection by beta-1 HPV5, and gamma 11 and 12 species, has been demonstrated to be associated with incident HNC [7].…”

“…Compared with the general population, prevalence of oral infection by mucosal HPVs is higher in men who have sex with men (MSM), particularly in those living with HIV-1 infection [8,[11][12][13][14][15]. In a previous study, we showed that beta and gamma HPVs are abundantly present in oral specimens from MSM, and that oral infection by beta HPVs is significantly more common than that caused by alpha types, irrespective of HIV status [6].…”

Concurrent and Concordant Anal and Oral Human PapillomaVirus Infections Are Not Associated with Sexual Behavior in At-Risk Males

“…Previously, we investigated anal and oral HPV infections in MSM populations, and compared HIV-infected vs. HIV-uninfected subjects in terms of prevalence at the two sites [14,15]. Therefore, the comparison between HIV-infected and HIV-uninfected MSM will not be further discussed here.…”