Prospective study of genital human papillomaviruses and nonmelanoma skin cancer

Abstract

Genital high-risk human papillomaviruses (HPVs) cause cervical cancer and are also found in a small proportion of nonmelanoma skin cancers (NMSCs). We used cancer registry linkages to follow the 856,000 serum donors included in the Southern Sweden Microbiology Biobank or the Janus Biobank in Norway, for incident skin cancers occurring up to 30 years after serum donation. Serum samples taken before diagnosis of squamous cell carcinoma (SCC) (N 5 633), basal cell carcinoma (BCC) (N 5 1990) or other NMSC (N 5 153) and matched samples from control donors were tested for antibodies to the genital HPV types 16 and 18. Both HPV 16 and 18 were associated with increased risk for SCC [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.6 and OR 1.7, 95% CI 1.1-2.5, respectively] and other NMSC (OR 2.3, 95% CI 1.0-5.2 and OR 3.5, 95% CI 1.4-8.7, respectively), but not for BCC. Tumor blocks from HPV16 or 18 seropositive cases were tested with real-time polymerase chain reaction for presence of HPV16 or 18 DNA. No HPV18 DNA was found and only four of 79 SCC cases (two of which were from the perineum=perianal area), one of 221 BCC cases and zero of five cases with other NMSC contained HPV16 DNA. In conclusion, we found prospective evidence that HPV16 and 18 antibodies associate with SCC and other NMSC risk, but not with BCC risk. As only a small proportion of seropositive subjects had evidence of the corresponding HPV DNA in the tumor, most of this excess risk is likely to be due to confounders associated with genital HPV infection.Human papillomaviruses (HPVs) are divided into mucosal and cutaneous types, where the mucosal types infect anogenital or oral mucosa and the cutaneous types infect the skin. 1The high-risk types among the mucosal types are known to be the main cause of cervical cancer.2 A role of either mucosal or cutaneous HPVs in skin cancer in the general population is not established, although it has been suggested. 3HPV serology is a well-established method for detection of past or present HPV infections 4 and is frequently used both for epidemiological research and vaccine research. 5Serological studies of HPV antibodies in relation to nonmelanoma skin cancer (NMSC) have sometimes included the mucosal high-risk types 16 and 18, but have so far not found an association with NMSC. [6][7][8][9][10]

Do Beta-Human Papilloma Viruses Cause Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals?

“…"In the latter scenario, the higher rates of B-HPV associated with cSCC would be merely a consequence of the cSCC and not the cause. The findings of two large prospective studies [25,33] included in our review succeed in answering this question and strengthen the position of those Adjusted for age and sex and used Cox proportional hazards Did not observe any association with overall antibody positivity, antibodies to multiple β HPV types or to specific types previously shown to be associated with cSCC.…”

“…The last study in this category conducted by Andersson el al. [33] is the only prospective evidence of HPV 16 sero-positivity involvement in cSCC. This study did not analyze B-HPV types for cSCC association which represents a missed opportunity for more in-depth findings.…”

“…Category C: Sero-prevalence and Skin Biopsy DNA The third category "collected Sero-prevalence and Skin Biopsy DNA of B-HPV" included 4 studies with a total of 964 cSCC cases and 1,149controls/cohort [30][31][32][33]. This category is the second largest in this systematic review, consisting of 3 single institution case-control studies with relatively small sample sizes and one large cohort study.…”

“…This category is the second largest in this systematic review, consisting of 3 single institution case-control studies with relatively small sample sizes and one large cohort study. Only one of those studies performed type-specific analysis while another performed none B-HPV type-specific analysis (HPV types 16,18) and the remaining two studies did not perform any HPV type-specific analysis [33]. All the studies showed a significant association between the involvement of B-HPV skin DNA and cSCC.…”

Human papillomavirus type 197 is commonly present in skin tumors

“…HPV16‐positive skin cancers are not common. They have been found not only in the perianal and perineal region, but also in other parts of the body . Infection of the skin by viruses originating from anogenital mucosal surfaces, mediated by the fingers, has been reported …”