Cutaneous β HPVs, Sun Exposure, and Risk of Squamous and Basal Cell Skin Cancers in Australia

Background: Sun exposure causes cutaneous squamous (SCC) and basal cell (BCC) carcinomas. Human papillomavirus (HPV) infection might cause SCC.

Methods: We examined associations of β and γ HPV infection in skin-swab DNA and serum antibodies with skin cancer risk, and modification of the carcinogenic effects of sun exposure by them, in case-control studies of 385 SCC cases, 832 BCC cases, and 1,100 controls nested in an Australian prospective cohort study (enrolled 2006-2009).

Results: Presence of β-1 and β-3 HPV DNA appeared to increase risks for SCC and BCC by 30% to 40% (P adjusted <0.01). BCC was also associated with genus β DNA, OR = 1.48; 95% confidence interval (CI), 1.10 to 2.00 (P adjusted <0.01). Associations were strengthened with each additional positive β HPV DNA type: SCC (OR = 1.07; 95% CI, 1.02-1.12) and BCC (OR = 1.06; 95% CI, 1.03-1.10), Ptrend<0.01. Positivity to genus β or γ in serology, and genus γ in DNA, was not associated with either cancer. There was little evidence that any β HPV type was more strongly associated than others with either cancer. A weaker association of sun exposure with SCC and BCC in the presence of β-3 HPVs than in their absence suggests that β-3 HPVs modify sun exposure's effect.

Conclusions: Our substantive findings are at the level of genus β HPV. Like SCC, BCC risk may increase with increasing numbers of β HPV types on skin.

Impact: The consistency in our findings that HPV infection may moderate the effects of sun exposure, the main environmental cause of SCC and BCC, merits further investigation.