Dr. Annarosa Del Mistro, MD

Research topic

Studies on natural history and determinants of cervical carcinogenesis by HPV aimed at improving cervical cancer prevention by a more precise cancer risk assessment, larger participation of the target population to organized cervical cancer screening programmes and tailored treatment. Studies on oropharyngeal cancer (OPSCC) and oral infection to assess the causal involvement of HPV and the clinical correlates.

Background

A subset of HPV types, defined as high-risk HPV (hrHPV), are the causal agents of all cervical carcinomas and a subgroup of OPSCC. Cervical cancer is now preventable by effective primary (prophylactic vaccines) and secondary (organized screening programmes) measures. Evidence-based protocols for more effective and tailored risk assessment of women with cervical hrHPV infection and treatment of potentially progressive high-grade pre-neoplastic lesions, as well as how to best screen vaccinated women, are being actively investigated by several groups. On the other hand, HPV-driven OPSCC is a recently identified new entity, characterized by a better prognosis than classic (driven by smoking and alcohol) OPSCC, large variations in geographic distribution and an increase over time trend; the assessment of HPV causal involvement is clinically relevant for the management of the patients, and the diagnostic work-out needs the demonstration of HPV causal involvement.

Research achievements

The studies conducted by the team, mostly as multicentric trials (the most important being NTCC, New Technologies in Cervical Cancer screening, started in 2002), have assessed the geographical distribution of cervical, anal and oral type-specific HPV infections and related lesions; have demonstrated the higher efficacy of HPV testing in the prevention of cervical cancer (leading to the reccomendation by the Ministry of Health to implement HPV testing as primary test for cervical screening in all the Italian regions by 2018, and the team is one of the three centralized laboratories in Veneto); have defined the screening protocol (women’s age, screening interval, HPV assays to be used and laboratory quality control requirements, triage assays); have assessed the prevalence of HPV-driven HNSCC in North-East Italy and defined a diagnostic algorythm. These studies have also led the team to collaborate with external Italian (i.e., CPO, Torino; ISPO, Firenze) and international research groups (i.e., IARC, Lyon, France; DKFZ, Heidelberg, Germany).

Conclusions and perspectives

The ongoing studies are evaluating HPV genotyping, and methylation of cellular and viral genes as new biomarkers for cervical cancer prevention on NTCC stored samples (with long-term longitudinal assessment of their clinical utility); mRNA HPV testing in comparison to cytology and p16/ki67 expression as triage tools in a new randomized multicentric trial (NTCC2); the same biomarkers are being evaluated as prognostic parameters to conservatively manage CIN2 lesions in young women. HPV-driven OPSCCs have been increasing over time in the last two decades also in North-East Italy, and the prospective study is ongoing to evaluate possible predictive biomarkers.