March 2020

Dr George Kravvas is a dermatology registrar and first year MD student funded by an anonymous donation to the British Skin Foundation.  Dr Kravvas works under the supervision of Professor Chris Bunker at University College, London (UCL) and Dr Magnus Lynch at Kings College, London (KCL).   His research focuses on the genetic alterations that link male genital lichen sclerosus, penile intraepithelial neoplasia, and penile squamous cell carcinoma. 

Background

Male genital lichen sclerosus (MGLSc) is an uncommon skin disease of uncircumcised individuals.  Prof. Bunker’s previous work suggests that MGLSc is due to the combination of a) long-term exposure of susceptible skin to urine, and b) occlusion caused by the foreskin.  MGLSc leads to inflammation and scarring, which can then result in sexual and urological difficulties, as well as an increased risk of developing penile precancer and cancer (penile squamous cell carcinoma or PSCC).

PSCC itself is fortunately a relatively rare cancer in the UK but is a mutilating disease with a high mortality.  Worldwide it is mainly seen in developing countries where circumcision is not routinely practiced. The pathway to PSCC is thought to be two-fold via two distinct precancerous situations, known as undifferentiated and differentiated penile intraepithelial neoplasias - PeINs.  Undifferentiated PeIN is by far the commonest of the two and is linked to infection with the human papilloma virus (HPV or wart virus). Differentiated PeIN is much rarer and has been linked to MGLSc.

Even though an association has been drawn between MGLSc, differentiated PeIN, and PSCC, the exact disease process is not fully understood.

In line with the pathway that has been demonstrated to occur in other precancerous conditions, the UCL/KCL investigators postulate that a similar process occurs in penile skin, whereby the stepwise mutation and accumulation of affected genes characterises the progression of MGLSc to PeIN and eventually PSCC.

Dr Kravvas says:

Through this research project the aim is to look at genetic changes that may be present in the above-mentioned conditions.  To do so, I intend to test diseased penile tissue that is obtained from affected patients. I will use this information in two different ways.

Firstly, I am looking to identify the common mutations that might occur in the affected skin of patients with MGLSc, PeIN, and PSCC.

Secondly, I aim to look for correlations between the mutations identified in each group, in order to understand whether a stepwise process of mutations takes place, leading to the progression of lichen sclerosus to penile precancer and penile cancer.

Finally, I aim to test the sampled tissues for the presence of the HPV virus in order to identify whether its presence affects the stepwise progression between these three conditions.

The team and I would like to thank the British Skin Foundation (and the anonymous donor) for supporting this study.

Dr George Kravvas

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