Merkel cell polyomavirus (MCPyV) DNA was detected in 88% of Merkel cell carcinomas in contrast to 16% of other skin tumors. MCPyV was also found in anogenital and oral samples (31%) and eyebrow hairs (50%) of HIV-positive men and in forehead swabs (62%) of healthy controls. MCPyV thus appears to be widespread.

As the detection rate of HPV‐DNA in anal carcinoma commonly exceeds 90%, a comparison between sole HPV‐positive and HPV‐negative cancers with respect to treatment response following chemoradiotherapy (CRT) and long‐term oncological outcome is challenging. Against this background, we aimed to assess HPV types and HPV DNA load in formalin‐fixed paraffin‐embedded tissue (FFPE) of 95 patients treated with standard CRT for anal cancer to correlate viral load (≤/> median) with local failure, distant metastases, cancer‐specific (CSS) and overall survival (OS) rates. Various clinicopathologic parameters and the immunohistochemical marker p16^INK4a were evaluated for any correlation with HPV16 DNA load and were included in uni‐ and multivariate analyses. The overall prevalence of HPV DNA was 95.8% with HPV16 monoinfection being the most commonly encountered HPV type (78.9%), followed by HPV16 and 31, 35, 39, 44, 58, 66 and 81 dual infection in 9 patients (9.5%). HPV16 DNA load was significantly associated with p16^INK4a expression (p = 0.001). Patients with HPV16 DNA load ≤ median and low p16^INK4a expression showed significantly worse local control (HPV16 DNA load: univariate p = 0.023, multivariate p = 0.042; p16^INK4a: univariate p = 0.021), and OS (HPV16 DNA load: univariate p = 0.02, multivariate p = 0.03). Moreover, a combined HPV16 DNA load and p16^INK4a variable revealed a significant correlation to decreased local failure, and increased CSS and OS (p = 0.019, p = 0.04 and p = 0.031). In conclusion, these data indicate that HPV16 DNA load and p16^INK4a expression are significant prognostic factors for local tumor control and overall survival of patients with anal SCC following CRT.

Merkel cell polyomavirus (MCPyV) is a ubiquitous virus replicating in human dermal fibroblasts. MCPyV DNA can be detected on healthy skin in 67–90% of various body sites, and intact virions are regularly shed from the skin. Infection occurs early in life, and seropositivity increases from 37 to 42% in 1- to 6-year-olds to 92% in adults. Merkel cell carcinoma (MCC) is a rare but very aggressive neuroendocrine tumor of the skin. It develops mainly on sun-exposed areas as a fast-growing, reddish nodule. Two MCC entities exist: about 80% of MCC are MCPyV-associated. Tumorigenesis is driven by viral integration into the host genome and MCPyV oncogene expression. In MCPyV-negative MCC, UV radiation causes extensive DNA damage leading to the deregulation of the cell cycle. In recent decades, MCC incidence rates have increased worldwide, e.g., in the United States, from 0.15 in 1986 to 0.7/100,000 in 2016. Risk factors for the development of MCC include male sex, older age (>75 years), fair skin, intense UV exposure, and immunosuppression. Projections suggest that due to aging populations, an increase in immunosuppressed patients, and enhanced UV exposure, MCC incidence rates will continue to rise. Early diagnosis and prompt treatment are crucial to reducing high MCC morbidity and mortality.

Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), an aggressive nonmelanoma skin tumour. MCC incidence has been rising in the last decades. Immunocompromised individuals such as HIV-infected patients have an increased risk for MCC development. MCPyV is found – mostly integrated into the host genome – in approximately 80% of MCC. The causal role of MCPyV in MCC development has been corroborated by several recent studies. Cutaneous MCPyV infection is acquired early in life and is widespread in the general population. In HIV-positive patients, MCPyV-DNA has been detected on the skin, on oral and anogenital mucosa, and in plucked eyebrow-hairs. Compared with healthy controls, MCPyV prevalence is increased in HIV-infected individuals and severe HIV-related immunosuppression is associated with elevated cutaneous MCPyV-DNA loads. This could explain the increased MCC risk found in HIV-infected individuals. MCC in HIV-infected patients occurs at a relatively young age and frequently on sites not exposed to sunlight. Guidelines for screening and early detection of MCC should be developed for HIV-positive patients. Future studies should evaluate changes in MCC incidence rates in HIV-infected individuals and analyse the effect of immune restoration by (early) antiretroviral therapy on MCC incidence and on cutaneous MCPyV load.