Beta Human Papillomavirus and Associated Diseases

Abstract

The cutaneous human papillomavirus (HPV), mostly from β- and γ-HPV genus, is ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of β-HPVs and cutaneous squamous cell carcinoma (cSCC) development was initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis. Likewise, immunosuppressed organ transplant recipients have an increased susceptibility to β-HPV infections in the skin as well as to cSCC development. Although ultraviolet radiation (UVR) is the main risk factor of cSCC, experimental data points toward β-HPVs as co-carcinogens, which appear to be required solely at early stages of skin carcinogenesis by facilitating the accumulation of UVR-induced DNA mutations. Several epidemiological studies relying on different biomarkers of β-HPV infections have also been conducted in immunocompetent individuals to access their association with cSCC development. Additionally, in vivo and in vitro studies are presenting cumulative evidence that E6 and E7 proteins from specific β-HPVs exhibit transforming activities and may collaborate with different environmental factors in promoting carcinogenesis. Nevertheless, further research is crucial to better understand the pathological implications of the broad distribution of these HPVs.

Role of E6 in Maintaining the Basal Cell Reservoir during Productive Papillomavirus Infection

“…Low-risk alphapapillomaviruses generally cause benign warts, with beta and gamma types typically associated with only persistent asymptomatic infections in immunocompetent individuals ( 1 ). Although beta PVs are part of the normal commensal microbial flora ( 15 ), they can cause cutaneous squamous cell carcinoma (cSCC) in patients suffering from epidermodysplasia verruciformis (EV) ( 16 , 17 ). PV infection typically occurs following a microwound, which allows virus particles to access the mitotically active basal cells on the basal lamina (reviewed in reference 18 ), which are responsible for the maintenance and replenishment of all layers of the skin.…”

Beta HPV Deregulates Double-Strand Break Repair

“…Unlike tumorigenic “high risk” alpha genus HPVs, beta genus HPV (beta HPV) infections occur in cutaneous epithelia [ 11 , 12 ]. In patients with a rare genetic disorder, epidermodysplasia verruciformis or EV, beta HPV infections persist and promote nonmelanoma skin cancer (NMSC) [ 13 , 14 , 15 , 16 ]. In EV patients, HPV5 and HPV8 are enriched in cutaneous squamous cell carcinoma (cSCC), which frequently occurs in sunlight exposed areas [ 16 , 17 ].…”

“…In patients with a rare genetic disorder, epidermodysplasia verruciformis or EV, beta HPV infections persist and promote nonmelanoma skin cancer (NMSC) [ 13 , 14 , 15 , 16 ]. In EV patients, HPV5 and HPV8 are enriched in cutaneous squamous cell carcinoma (cSCC), which frequently occurs in sunlight exposed areas [ 16 , 17 ]. Infection with these viruses also increases the risk of cSCC in organ transplant recipients (OTRs) who are receiving immunosuppression treatment [ 4 , 5 , 6 , 7 ].…”

Beta-Genus Human Papillomavirus 8 E6 Destabilizes the Host Genome by Promoting p300 Degradation

“…This review discusses these topics and others, with a particular focus on HPV8 E6. β-HPV E6 functions not related to p300 binding have been extensively reviewed [ 25 , 26 , 27 , 28 ] and will not be discussed in this review.…”