Human papillomaviruses of skin and genital lesions

Abstract: Around 5% of all cancer cases worldwide are caused by human papillomavirus (HPV) which has been established as the cause of cervical cancer and genital warts (condylomas). Cutaneous HPV types have been weakly associated with non-melanoma skin lesions such as squamous cell carcinoma (SCC) and actinic keratosis (AK). We have analyzed skin and genital lesions for presence of HPV-DNA in order to search for unknown and known HPV types. As an attempt to identify women at risk for development of high-grade cervical lesions, HPV E6/E7 mRNA expression was analyzed among women with minor cervical abnormalities. Metagenomic sequencing identified 15 known HPV types, four previously known HPV types and two novel putative types in cutaneous lesions (n=369) and swabs from top of the lesions (n=142) (SCC, AK and keratoacanthoma). The prevalence and viral load of characterized HPV155 and SE46 HPV-isolate was investigated in patients with different cutaneous lesions. HPV155 and SE46 were both found in 2% of patients. HPV178 was characterized from a swab of normal skin next to an actinic keratosis. A baseline of 36 different HPV types of the alphapapillomavirus genus in 93.9% of condyloma swab samples before HPV vaccination was established. Extended testing among subjects initially negative for HPV (n=50), found 21 patients with cutaneous types of HPV, including novel HPV153. After metagenomic sequencing (n=40) of HPV-negative condylomas, we detected four different HPV types of the alphapapillomavirus genus but also six known HPV types, three previously described putative HPV types and 22 novel putative types of the beta and gammapapillomavirus genera. Novel HPV175 and HPV180 were isolated from the condyloma. HPV153, 175 and 180 are all gamma types. In the study of high-risk HPV mRNA expression of HPV-DNA positive minor cytological abnormalities (ASCUS; atypical squamous cells of undetermined significance, n=211, and CIN1; cervical intraepithelial neoplasia grade 1, n=131) we observed a high sensitivity (97.2%) but low specificity (10.2%) for detecting future high grade cervical lesions (CIN2+). Presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among high-risk HPV DNA positive women with ASCUS and CIN1. The absence of HPV mRNA demonstrated a tendency for protection against future development of CIN3.