Natural History of Incident and Persistent Cutaneous Human Papillomavirus and Human Polyomavirus Infections

Abstract

Background: Cutaneous human papillomaviruses (cuHPV) and polyomaviruses (HPyV) have been implicated in skin cancers; however, interpretation of findings across studies is complicated by limited understanding of the natural history of these infections across normal tissue types.

Methods: In total, 675 eyebrow hair (EBH) and skin swab (SSW) samples were collected from 71 skin cancer screening patients every 6 months over 2 years and measured for presence of β-HPV, γ-HPV, and HPyV. Incidence, persistence, and clearance of cuHPV/HPyV were estimated, and risk factors associated with infection were examined.

Results: Prevalence, incidence, and persistence of β-HPV, γ-HPV, and HPyV were consistently higher in SSW than in EBH, with types 5, 24, 49, 76 and Merkel cell polyomavirus (MCPyV) having incidence rates greater than 20 per 1000 person-months. Prevalent γ-HPV EBH infections persisted more often in women (P = .024), incident β-HPV EBH infections persisted less often among individuals with history of blistering sunburn (P = .019), and prevalent MCPyV SSW infections persisted more often in those with a history of skin cancer (P = .033).

Conclusions: Incidence and persistence of cuHPV/HPyV were observed in SSW and EBH; however, none of the risk factors examined were commonly associated with cuHPV/HPyV infections across normal tissue types.

Keywords: basal cell carcinoma; cutaneous HPV; incidence; natural history; persistence; polyomavirus; risk factors; squamous cell carcinoma.

Figure 1.

Patterns of 6-month repeated cutaneous HPV infection. The figure depicts the patterns of repeated cutaneous HPV infection using HPV 38 viral DNA in skin swabs as an example. Boxes 2, 4, and 5 correspond to how prevalent infections, persistence of prevalent infections, and clearance of prevalent infections were coded, respectively. Boxes 8, 9, and 10 together correspond to incident infections, box 15 corresponds to persistence of incident infections, and box 16 corresponds to clearance of incident infections. Abbreviation: HPV, human papillomavirus.

Figure 2.

Incidence rates of cutaneous HPV and HPyV. The type-specific incidence rate of (A) β-HPV types (B) γ-HPV types and (C) HPyV types as measured in EBH and SSW. Overall, type-specific incidence rates were higher as measured in SSW than that in EBH. Types with zero incidence in both EBH and SSW were excluded from the figure (γ-HPV: 48, 60, 88, 95, 101, 103, 108, 112, 116, 119, 171, and 184, and HPyV 6). Abbreviations: EBH, eyebrow hair; HPV, human papillomavirus; HPyV, human polyomavirus; SSW, skin swab.

Figure 3.

Correlation between prevalence, incidence, and duration of cutaneous HPV infection. Type-specific scatterplot showing the relationship between prevalence and incidence × duration for (A) β-HPV types measured in EBH, (B) β-HPV types measured in SSW, (C) γ-HPV types measured in EBH, and (D) γ-HPV types measured in SSW. Duration was estimated as 1 minus clearance and robust linear regression was used to summarize the relationship across types. Abbreviations: EBH, eyebrow hair; HPV, human papillomavirus; SSW, skin swab.

Figure 4.

Prevalence, incidence, persistence, and clearance of cutaneous HPV and HPyV at the patient level. The viral infection status across 5 visits over a 2-year period summarized at patient level: prevalent, the percent of patients who had infection at baseline among all patients; prevalent that persisted, the percent of patients who had at least 1 prevalent infection that persisted among those who had prevalent infections; percent that cleared, the percent of patients who had at least 1 prevalent infection that cleared among those who had prevalent infection; incident, the percent of patients who had at least 1 incident infection among all patients; incident that persisted, the percent of patients who had at least 1 of incident infection that persisted among those who had incident infection; incident that cleared, the percent of patients who had at least 1 incident infection that cleared among patients who had incident infection. Abbreviations: EBH, eyebrow hair; HPyV, human polyomavirus; HPV, human papillomavirus; SSW, skin swab.