Markers of Cutaneous Human Papillomavirus Infection in Individuals with Tumor-Free Skin, Actinic Keratoses, and Squamous Cell Carcinoma

Abstract

Separately, actinic keratosis (AK) and cutaneous squamous cell carcinoma (SCC) have been associated with cutaneous human papillomavirus (HPV) infections. To further explore the association between HPV infection and SCC development, we determined markers of cutaneous HPV infection within a single population in persons with precursor lesions (AK), cancerous lesions (SCC), and without. Serum and plucked eyebrow hairs were collected from 57 tumor-free controls, 126 AK, and 64 SCC cases. Presence of HPV L1 and E6 seroreactivity and viral DNA were determined for HPV types 5,8,15,16,20,24, and 38. Significant positive associations with increasing severity of the lesions (controls, AK, and SCC, respectively) were observed for overall HPV L1 seropositivity (13%, 26%, and 37%) and for HPV8 (4%, 17%, and 30%). In parallel, the proportion of L1 seropositive individuals against multiple HPV types increased from 14% to 39% and 45%. The overall E6 seroreactivity, however, tended to decline with AK and SCC, especially for HPV8 (21%, 11%, and 2%). HPV DNA positivity was most prevalent in the AK cases (54%) compared with the SCC cases (44%) and the tumor-free controls (40%). Among all participants, there was a positive trend between overall HPV DNA positivity and L1 seropositivity, but not E6 seropositivity. Taken together, our data suggest that cutaneous HPV infections accompanied by detectable HPV DNA in eyebrow hairs and HPV L1 seropositivity, but not E6 seropositivity, are associated with an increased risk of AK and SCC. (Cancer Epidemiol Biomarkers Prev 2006;15(3):529 -35)

Prevalence and associated factors of betapapillomavirus infections in individuals without cutaneous squamous cell carcinoma

“…The Dutch study participants were selected from a case-control study investigating several environmental and genetic risk factors for skin cancer (De Hertog et al, 2001;Struijk et al, 2003). Briefly, 278 controls with no history of any type of skin cancer who were age-and sex-matched to a series of cases with SCC were recruited at the ophthalmology outpatient clinic at the Leiden University Medical Center according to criteria that have been described by Struijk et al (2006). The 257 Italian control participants with no skin cancer history were selected from the dermatology out-patients clinics at the Istituto Dermopatico Dell'Immacolata (Rome, Italy).…”

“…Recent epidemiological studies suggest that these betaPV types also play a role in the pathogenesis of cutaneous SCC in the general population. Seroreactivity to betaPV types has been found to be associated with non-melanoma skin cancer (Andersson et al, 2008;Feltkamp et al, 2003;Karagas et al, 2006;Struijk et al, 2006). Also, associations have been found between the detection of betaPV DNA in plucked eyebrow hairs and actinic keratoses (AK) (Boxman et al, 2001;Struijk et al, 2006) and cutaneous SCC Struijk et al, 2003Struijk et al, , 2006.…”

An analysis of clustering of betapapillomavirus antibodies

“…This is partly because no study to date has shown an unequivocal association between cancer and any specific type among non-EV patients. Evidence is accumulating to suggest that the presence of antibodies to multiple bPV types may be associated with the aetiology of cutaneous SCC (Karagas et al, 2006;Struijk et al, 2006), although it may be that multiplicity is a marker of infection with a specific oncogenic type or group of bPVs. Our study suggests that people who are unaffected by SCC can be discriminated on the basis of the number of viruses to which antibodies can be detected, lending some support to the hypothesis that multiplicity of infection is causally associated with SCC.…”

“…Case-control studies have been conducted to examine further the relationship between betapapillomaviruses (bPVs) and SCC, in which bPV DNA in plucked eyebrow hairs, and serum antibodies, have been used as markers of infection. Overall, these studies have found associations between the presence of viral DNA or antibodies and SCC Karagas et al, 2006;Struijk et al, 2003Struijk et al, , 2006, although the data have been somewhat inconsistent. Importantly, no high-risk types have been identified.…”

A case‐control study of cutaneous squamous cell carcinoma among Caucasian organ transplant recipients: The role of antibodies against human papillomavirus and other risk factors

“…19 These findings were consistent with a study in which HPV-DNA from the beta genus of species 2 predominated in SCC compared to healthy skin samples. 37 The natural history of cutaneous HPV types is not well understood 24 and the concordance between HPV-DNA in skin biopsies 18 or in plucked hairs 17 and antibody detection has been low. In comparison to the clear results relating HPV 16 and 6 to self-reported histories of cervical cytological abnormalities or genital warts, the role of any of the 34 HPV types examined in relation to SCC remains unclear.…”