Current projects related to cancer caused by HPV infections

Oncogenic types of the human papillomaviruses are major carcinogens causing about 5 % of the global cancer burden. In particular cancers of the uterine cervix, the anus, vulva and vagina as well as of the oropharynx may be caused by persistent infection with high risk HPV- types (HR-HPVs).

The carcinogenic activity of HR-HPVs is linked to the activated expression of two viral genes referred to as E6 and E7. The major carcinogenic function of these genes relies in their ability to cause chromosomal instability by multiple interactions with host cell proteins.

We are interested to explore how these genes can trigger chromosomal instability and which epigenetic mechanisms initiate their activated expression in specialized host cells that subsequently can develop into cancer cells.

Recent data from our lab and others suggest that these mechanisms are likely to be drugable by inhibitors of the DNA methyltransferases. This observation prompted us to develop topical treatments for transforming HPV infections.

We further developed biomarkers (p16^INK4a) to highlight cells with activation of the HPV oncogenes E6 and E7 that are now extensively  used as specific biomarkers for “transforming” HPV infections in various clinical applications. 

Finally, overexpression of p16^INK4a prompted us to hypothesize that an immune response against p16^INK4a may help to reject transforming HPV infections. We are therefore actively working on vaccines targeting the p16^INK4a antigen.

Details of our research on HPV-associated cancers are outlined for our main research directions:

• Biomarkers and prevention
• Emerging technologies in cervical cancer screening (ETiCCS)
• The Human Papillomavirus Infection and Oropharyngeal Cancer Consortium (HOCC)
• Epigenetics
• Vaccines
• Genomic instability mediated by papillomavirus oncogenes (GIMPO)

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