Viral Skin Carcinogenesis
Eggert Stockfleth, MD
Dr Stockfleth reviewed the latest data and the role of the human papillomavirus (HPV) in skin cancer. HPV is a very stable, host-specific virus, which it is why it is referred to as “human” papillomaviruses. HPV is a frequent virus in most everyone. The most known strains of HPV are 16 and 18. HPV also has a very special DNA from the oncogenic type (E6 and E7). Currently, there are two prophylactic quadrivalent vaccines available, which harbor HPV 6, 11, 16 and 18.
It’s important to know that the target cell for HPV is the keratinocyte. HPV types can infect skin tumors and mucosa tumors.
Currently, there are over 150 human papillomavirus types. These types can be distinguished by either alpha type, the wart-associated types, or cutaneous types, which are mainly the beta- or gamma-PV types.
Genital HPV, as we know, is one of the most frequently transmitted diseases; however, don’t forget that most of us already have these viruses for life.
Transmission of cutaneous HPV is through skin contact. Yet, the virus is very stable so can remain for several days. Probably, the best known oncogenic HPV types for cutaneous HPV are types 5 and 8.
Cutaneous Squamous Cell Carcinoma
SCC is prevalent on 80% of sun-exposed areas in cutaneous HPV and the main risk factor is UV radiation (UVA and UVB). Dr Stockfleth and colleagues found that 118 genes were identified as differentially expressed in skin cancer.
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. Chronic UV exposure leads to a local down-regulation of immune response; therefore, leading to an increased risk of developing skin cancer. HPV blocks apoptosis and the repair mechanism which can lead to SCC.
What are the criteria to define a causal role in disease by infectious agents?
Biology of HPV
- Presence of HPV in (pre)cancer cells
- Expression of viral genes in (pre)cancer cells
- Transforming properties (in vitro and in vivo models)
- Relative Risk (RR) and Odds Ratio (OR)
What about cellular networks?
Research on cellular networks over the years has led researchers to look for the “guardian” genes.
A 2011 publication by Dr Stockfleth and colleagues, looked at the interaction of cutaneous HPV 23. Of note, HPV 23 and 38 are the most prevalent types of virus and play a role in development of skin cancer. These HPV subtypes (23 and 38) induced anti-apoptotic effects in UV-damaged cells through the expression of two oncogenic proteins E6 and E7 that lead to persistence and accumulation of further mutations. Data from this paper suggest that cutaneous HPV23 E6 protein directly targets HIPK2 function; therefore, HIPK2 was identified as the guardian gene.
Research is still ongoing regarding identification of other viruses, vaccination and treatment.