The Role of HPV in Skin Cancer

Eggert Stockfleth, MD

In this presentation, Dr Stockfleth reviews the latest data and the role of the human papillomavirus (HPV) in skin cancer.

We know that HPV is very stable. The virus is host specific and has a very special DNA from the oncogenic type (E6 and E7). HPV is approximately 45-55 nm in size and its genome size is 8kb.

Currently, there are 200 different types of HPV.

HPV is one of the most frequently transmitted STDs.

HPV Prevention Strategies
  • Reduce duration of infectiousness through treatment
  • Decrease transmission efficiency with consistent condom use
  • Reduce/limit  number of sex partners
  • Quadrivalent HPV vaccine
    • Gardasil® : protects against HPV types 6, 11 (responsible for >90% EGWs) 16, 18 (responsible for 70% cervical cancer)
    • Administered as 3 injections over 6 month period (0,2,6 mo’s)
    • ACIP recommended: females 9-26 yrs of age

Human Immunity

Therapeutic Modalities for External Genital Warts (EGWs)

Various therapeutic modalities exist for the treatment of EGWs. These can be both patient-applied or provider-administered. Patient applied therapies include Imiquimod cream, Podofilox gel/solution, and Sinecatechins ointment. Provider-administered therapy includes Trichloracetic acid, Bichloroacetic acid, Cryotherapy, Podophyllin resin, laser therapy, excision/electrosurgery and interferon.

The Role of Cutaneous HPV in Skin Carcinogenesis

The association between HPV and non-melamona skin cell was first described in patients with epidermodysplasia verruciformis (EV). Cutaneous HPV types include HPV 5, 8, 9, 12, 14, 15, 17, 19-25, and many more. 30-60% of HPV patients develop multiple cutaneous squamous cell carcinomas (SCCs) on sun-exposed sites after 10-30 years. These SCCs harbor the ongenic types of HPV 5 and HPV 8 in more than 90% of cases.

Cutaneous HPV and SCC

SCC is prevalent on 80% of sun-exposed areas in cutaneous SCC and the main risk factor is UV radiation (UVA and UVB).  There are multiple risk factors during skin carcinogenesis. With a functional immune system, your body can repair DNA image or lead to programmed cell death, i.e, apoptosis.

The p53 gene is involved in almost 75% of all skin cancer. HPV positive cells can block p53; therefore, blocking apoptosis.

Criteria to Define a Causal Role in Disease by Infectious Agents (HPV and Skin Cancer (SCC))

Biology of HPV:

  • Presence of HPV in (pre)cancer cells
  • Expression of viral genes in (pre)cancer cells (E6, E7)
  • Transforming properties (in vitro and in vivo models)


  • Relative risk (RR) and Odds Ratio (OR)

HPV 23 was the most prevalent type of virus in immunocompetent and immunosuppressed OTR. The accumulation of the HPV23 E6 protein is caused by HIPK2.  HPV23 E6 interacts with HIPK2 upon UV-induced DNA-damage; therefore, inhibiting HIPK2.p53 complex formation which is the key event in the induction of UV-induced apoptosis.

Cutaneous HPV infected cells may overcome UV-induced apoptosis and be causal in the early onset of skin carcinogenesis.


Current data suggests that cutaneous HPV may play a role in the development of cutaneous SCC.  HPV induced anti-apoptotic effects in UV-damaged cells may lead to persistence and accumulation of further mutations.

Research is still ongoing regarding vaccination and treatment.