Cutaneous alpha, beta and gamma human papillomaviruses in relation to squamous cell carcinoma of the skin: A population‐based study

Abstract

Human papillomavirus (HPV) infection is common worldwide and, in immunodeficient populations, may contribute to the pathogenesis of keratinocyte cancers, particularly squamous cell carcinomas (SCC). However, their role in SCC in the general population is less clear. We conducted a comprehensive analysis to investigate the independent effects of seropositivity for cutaneous alpha, beta and gamma HPV types on risk of SCC, and a meta-analysis of the available literature. In a population-based case-control study from New Hampshire, USA (n=1408), histologically-confirmed SCC cases and controls were tested for L1 antibodies to alpha, beta and gamma cutaneous HPV types 2–5, 7–10, 15, 17, 20, 23, 24, 27b, 36, 38, 48–50, 57, 65, 75–77, 88, 92, 95, 96, 101, 103, and 107 using multiplex serology. An increasing risk of SCC with number of beta HPVs to which an individual tested positive was observed even among those seronegative for gamma types (P for trend = 0.016) with an odds ratio of 1.95 (95% confidence interval (CI) = 1.07–3.56) for four or more beta types positive. In a meta-analysis of six case-control studies, increased SCC risks in relation to beta HPV seropositivity were found across studies, (meta odds ratio = 1.45, CI = 1.27–1.66). While the prevalence of gamma HPVs assayed was somewhat higher among SCC cases than controls, the association was only weakly evident among those seronegative for beta HPVs. Overall, the association between cutaneous HPVs and skin cancers appears to be specific to SCC and to genus beta HPVs in a general US population.

Improved detection reveals active β-papillomavirus infection in skin lesions from kidney transplant recipients

“…Seroepidemiological studies have associated skin cancer in organ transplant recipients with the presence of anti-b-HPV antibodies, and PCR-based studies have identified b-HPV DNA in over 80% of skin tumors from these patients. 22,[35][36][37][38][39][40][41][42][43] Despite these findings, a causal role of these viruses has been difficult to verify because of their ubiquitous prevalence in the general population and their absence in some cancers. 25,44 The major weakness of the available studies is that the proposed association is mostly based on the presence of viral DNA in tumor tissues or positive antibody responses.…”

Human papillomavirus and posttransplantation cutaneous squamous cell carcinoma: A multicenter, prospective cohort study

“…βPV‐infected cells may have impaired DNA repair and decreased sensitivity to apoptosis induced by ultraviolet radiation (UVR), facilitating escape from normal cellular defense mechanisms 9, 13. A substantial body of epidemiologic data show an association between HPV infection and cSCC,12, 20, 21, 22, 23, 24 in particular, in OTRs 25, 26. In most studies, HPV infection has been determined by detection of serologic responses to a large series of βPV and sometimes γPV types12, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31 and less frequently by detecting genomic DNA from 1 or multiple HPV types in eyebrow hair or skin scrapings 20, 21, 25, 32, 33, 34…”

“…Case‐control studies in both OTR and immunocompetent populations have shown that the presence of βPV DNA or antibodies was associated with a 1.5‐ to 3‐fold increased risk of cSCC 12, 20, 21, 22, 23, 24, 25, 26, 29, 31, 32. It was not possible, however, to determine whether the βPV infection increases risk of cSCC development or whether cSCC formation promotes active proliferation of βPV.…”

Detection of HPV E7 Transcription at Single-Cell Resolution in Epidermis

“…Cutaneous β-HPVs are associated with SCCs in patients with the autosomal recessive disorder epidermodysplasia verruciformis (EV) (Gewirtzman et al, 2008). The burden of β-HPV infection predicts risk of subsequent development of SCC (Farzan et al, 2013), and antibodies to β-HPVs, suggesting active HPV infection, are associated with SCC in immunosuppressed patients (Genders et al, 2015). However, transcription of β-HPV RNA is not observed in healthy skin or in premalignant or malignant skin lesions (Arron et al, 2011), supporting a 'hit-and-run' role for β-HPVs in cutaneous carcinogenesis (Pfister, 2003).…”