Molecular Characteristics of HPV Positive anal Carcinoma
Severine Valmary-Degano, Jean-Luc Pretet, Franck Monnien, Rabah Hamlaoui, Elise Jacquin, Jean-Francois Bosset, Christiane Mougin, Bernadette Kantelip. University Hospital, Besançon, France; IFR133 - UFR SMP - Les Hauts du Chazal, Besançon, France
Background: Incidence of invasive anal carcinoma is increasing. Most anal invasive carcinoma is caused by high-risk human papillomaviruses (HPV) and HPV16 is the most prevalent type.
Design: HPV genotype distribution was determined in 86 diagnostic biopsies of anal cancers, collected between 1997 and 2007. Viral load and physical state of the viral genome were evaluated in HPV16 positive tumours with type-specific real-time PCR targeting E6, E2 and albumin genes. Expression of p16, Ki-67, p53 and p21 was also analyzed by immunohistochemistry. Biologic data were correlated with OS and PFS of patients to highlight theranostic factors.
Results: 80% of cases were squamous cell carcinoma and 97.5% of samples were positive for alpha-HPV DNA. HPV16 was the most prevalent genotype (90%), followed by HPV39 and HPV33 (3.75% each). Fully integrated HPV16 DNA estimated by the E2/E6 was observed in less than 10% of cases associated with a low viral load compared with cases containing either pure episomes or mixes of integrated and episomal DNA in which the HPV16 median load was at least higher of 2 log.
The majority of HPV16+ tumours expressed p16 (90%) and showed a high proliferation index (82%). In contrast a minority of tumours presented an overexpression of p53 (14%) and its target p21 presented a different expression pattern. An interim statistical study showed that p16 expression and absence of p53 expression seemed to be positive prognostic markers in term of progression free survival and overall survival.
Conclusions: The high prevalence of HPV16 is confirmed in this French series of anal carcinoma with a high viral load except in cases harbouring pure integrated HPV16 DNA. The subsequent deregulated p53 expression might predict response to radiochemotherapy.
Monday, March 19, 2012 1:00 PM
Poster Session II # 125, Monday Afternoon