The role of HPV in keratinocyte skin cancer development: A systematic review

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyze evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen’s disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n=372, 58.49%) and gamma HPV (n=256, 40.25%) and only a few (n=6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n=248, 55.98%) and gamma HPV (n=172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen’s disease lesions were mostly positive for beta (n=43, 55.84%) and alpha HPV (n=30, 38.96%), in contrast to the gamma genus (n=4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n=79, 50.31%) and an equal proportion between alpha (n=39, 24.84%) and gamma (n=39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen’s disease, squamous cell carcinoma, or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with no-melanoma skin cancer brings into perspective the idea of a beta HPV vaccine or a combined alpha and beta HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.