Abstract :
[en] Background
First identified in the 80s and comprising 68 strains, β-HPVs are the subject of a growing interest, in particular due to intriguing results showing that some genotypes (e.g. HPV8 or 38) could promote the development of precursor lesions of cutaneous squamous cell carcinoma (SCC).
Aim
This project aims at deciphering the role of β-HPV infections in non-melanoma skin carcinogenesis and is articulated around two main objectives:
1) Study how E6/E7 from some β-HPV strains (5, 8, 38, 49) potentiate the mutational effects of UVB irradiation.
2) Determine the involvement of β-HPV in a poorly characterized preneoplastic syndrome (Bowen’s disease).
Methods
In order to highlight these potential interactions (Aim 1), a high throughput screening (GPCA) was performed using a library of 200 cDNAs coding for proteins implicated in DNA damage/repair responses (created from ORFeomes 7.1 and 8.1).
In parallel to this first objective, an immunohistopathological characterization was performed on a panel of 163 patients with Bowen's disease (Aim 2). To do this, 5 immunohistochemical stainings (p16; Ki67, p53, caspase-3 and CD45) as well as HPV genotyping (luminex) were carried out.
Results
Using GPCA, we highlighted 26(e.g. APEX2, PNKP, ERCC2, UVSSA, …) potential interactions between β-HPV oncoproteins E6 (HPV5, 8, 38 and 49) and proteins involved in DNA repair pathways, as well as 14 (e.g. MPG, PNKP, RAD23A, ERCC2, …) potential interactions with E7.
Regarding the second objective, using immunochemistry, a more precise classification (several potential new subgroups) of Bowen's disease has been highlighted.
Conclusion
These promising results, still to be confirmed by Co-IP (ongoing), seem to support the hypothesis that beta-HPV could hijack host DNA repair pathways. Indeed, some of our targets play a key role in different repair pathways, especially in the NER and BER, two key pathways for repairing UV-induced breaks.
Moreover, immunohistochemistry has broadened our understanding of Bowen's disease and the role of beta-HPV, particularly by identifying novel potential subtypes detected in this cutaneous syndrome. As expected, we demonstrated that gynaecological biopsies are α-HPV-dependent. Surprisingly, photoexpose biopsies can be infected by α-HPV as well as β-HPV genotypes.
