Does Human Papillomavirus (HPV) increase the risk of skin cancer?

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From the Guidelines

Human Papillomavirus (HPV) does increase the risk of certain skin cancers, particularly squamous cell carcinoma, especially in immunocompromised individuals and those with specific genetic conditions. The relationship between HPV and skin cancer is complex, with certain HPV types, such as HPV 5 and 8, contributing to the development of non-melanoma skin cancers in specific populations 1. The risk of HPV-related skin cancer is significantly higher in immunocompromised individuals, such as organ transplant recipients, and those with rare genetic conditions like epidermodysplasia verruciformis 1. For the general population with normal immune function, the risk of HPV-related skin cancer is relatively low, but HPV-related skin cancers typically develop in sun-exposed areas, suggesting that UV radiation works synergistically with HPV infection to promote cancer development 1. Key points to consider include:

  • HPV vaccination, such as Gardasil 9, which primarily targets genital HPV types but may offer some cross-protection against skin cancer-causing types
  • Sun protection measures to reduce UV radiation exposure
  • Regular skin examinations, especially for those at higher risk, such as immunocompromised individuals and those with a history of skin cancer While most HPV infections clear naturally, persistent infections with high-risk types pose the greatest cancer risk, emphasizing the importance of prevention and early detection strategies 1.

From the Research

Human Papillomavirus (HPV) and Skin Cancer Risk

  • HPV is a small non-enveloped icosahedral virus that infects the keratinocytes of skin and mucosa 2.
  • The main cause of non-melanoma skin cancer is exposure to ultraviolet radiation (UVR), but cutaneous HPVs may act as a co-carcinogen with UVR 2, 3.
  • Beta-HPVs, particularly those from the beta genus, have been associated with an increased risk of cutaneous squamous cell carcinoma (SCC) 2, 4, 5.

Mechanism of HPV-Induced Skin Cancer

  • The "hit-and-run" hypothesis suggests that beta HPVs play a role in the early stages of tumor development, but are not necessary for the maintenance of the malignant phenotype 2, 3.
  • E6 and E7 oncoproteins from certain cutaneous HPV types have been shown to promote proliferation and circumvent cellular stresses induced by UV radiation 3.
  • The anti-apoptotic activities of E6 proteins from cutaneous HPV may lead to the persistence of DNA-damaged keratinocytes, increasing the risk of skin cancer 4, 5.

Epidemiological Evidence

  • Studies have reported a higher risk of SCC associated with certain EV/cutaneous HPV types, particularly in immunosuppressed patients 4, 5.
  • Epidemiological studies have also shown a higher prevalence of HPV DNA in skin tumors of patients with Epidermodysplasia verruciformis (EV) 2, 5.
  • The association between beta-HPVs and skin cancer has been observed in both immunocompromised and immunocompetent individuals 2, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cutaneous HPV and skin cancer.

Presse medicale (Paris, France : 1983), 2014

Research

HPV and skin carcinogenesis.

Papillomavirus research (Amsterdam, Netherlands), 2019

Research

Chapter 8: Human papillomavirus and skin cancer.

Journal of the National Cancer Institute. Monographs, 2003

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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