Viral-Associated Nonmelanoma Skin Cancers: A Review

Abstract

Nonmelanoma skin cancers are the most common malignancies in the United States, with over 1.3 million patients diagnosed yearly. Several types of nonmelanoma skin cancer and precancerous lesions have an associated viral pathogenesis, including epidermodysplasia verruciformis, verrucous carcinoma, bowenoid papulosis, Kaposi sarcoma, squamous cell carcinoma, and, most recently, Merkel cell carcinoma. It is now widely accepted that high-risk human papillomaviruses (HPVs) play a key role in pathogenesis of cervical and anogenital cancer. Currently, 108 types of HPV have been discovered. They can be divided into genera including alpha, beta, and gamma HPVs, which comprise the majority of cutaneous HPVs. The relationship between viruses and cancer is a popular focus of research in an era of AIDS and organ transplantation, where immunosuppression is not uncommon. The incidence of viral-related malignancies in these populations is increasing. Because of the widespread nature of these cutaneous malignancies, an evaluation of these conditions is valuable. This review of the literature will focus on the histologic aspects of viral-associated skin malignancies, as well as the epidemiology, etiology, and clinical aspects of these diseases.

Comprehensive analysis of human papillomavirus prevalence and the potential role of low-risk types in verrucous carcinoma

“…3,40 Previous studies concluded that verrucous carcinoma from mucosal areas are related to mucosal HPV types and verrucous carcinoma located in cutaneous areas are not specifically linked to any specific group of HPV. 41 In this study, we found that mucosal types were indeed restricted to mucosal lesions, that is, high-risk HPV in a verrucous carcinoma of the head and neck region and low-risk HPV types in giant condylomas of the anus and vulva, whereas cutaneous HPV types were detected in a verrucous hyperplastic lesion of the penis.…”

The Clinicopathologic and Molecular Aspects of Non-Melanoma Skin Cancer

“…(43,44) However the variable quantity of HPV in immunocompetent individuals can range between 27-70% depending on detection techniques. (32,44) Thus the type of HPV, β-papillomavirus species 2, may be more often associated with cSCC as opposed to the total amount of HPV DNA present. 32 Three theories have been suggested for the mechanism of HPV carcinogenesis: 1) UV radiation induced immunosuppression to explain an enhanced interaction between HPV and UV radiation, 2) E6/E7 oncoprotein-related changes in p53 and Rb tumor suppressor gene, and 3) integration of HPV DNA disrupting genomic stability.…”

“…32 Three theories have been suggested for the mechanism of HPV carcinogenesis: 1) UV radiation induced immunosuppression to explain an enhanced interaction between HPV and UV radiation, 2) E6/E7 oncoprotein-related changes in p53 and Rb tumor suppressor gene, and 3) integration of HPV DNA disrupting genomic stability. (32,45,46) . Viral expression of E6 and E7 oncoproteins can inactivate p53 and Rb tumor suppessor genes, leading to an uncontrolled system of cell proliferation and apoptosis.…”

“…(28)(29)(30) Genetically inherited skin conditions that have a known propensity of risk for developing cSCC are albinism, xeroderma pigmentosum, and epidermodysplasia verruciformis. (9,(31)(32) The strongest risk factors for NMSC mirror the etiologies and include Caucasian race, older age 55-75 years of age, male sex, a prior diagnosis of NMSC confers a 10-fold risk for recurrence, and immunosuppression, as well as genetic, chemical and environmental factors (See Table 2). Likewise sites of chronic inflammation, such as scars, sinus tracts, and burns, can also demonstrate more aggressive clinical behavior and a greater propensity to metastasize with an overall metastatic rate of 40%.…”

The role of human papillomaviruses in cancer progression

“…[31][32][33] Lesion persistency and progression are increased in both animals and humans with genetic, iatrogenic or acquired cell mediated immune deficiencies, such as in patients with severe combined immunodeficiency, [34] in immunosupressed organ recipient patients, [35] in patients with epidermodysplasia verruciformis [35] and sun-exposed sites of patients with non-melanoma skin cancer. [35][36][37] Moreover, HPVs can escape the immune system and down regulate the innate immune signalling pathways. [38] The clearance of high risk HPV types are believed to be harder since these types weaken the immune defences causing infection to continue and progress to neoplasias.…”