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Clinical characteristics and treatment outcome in p16 negative anal cancer
Catherine Burgos1, Calin Radu2, Sofia Heyman3
1Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. catherine.burgos.delgado@igp.uu.se.
Background:
Anal squamous cell carcinoma (ASCC) is linked to human papillomavirus infection with p16 being positive in about 85% of cases. Overall survival (OS) of ASCC is 60%-80%. Prognosis in p16 negative (p16-) ASCC is worse with an OS of 30%-60%. It is important to elucidate differences in p16+ and p16- ASCC characteristics and outcome.
Methods:
Consecutive ASCC patients (n = 380) treated with curative intent in Uppsala 2017-2022 were reviewed and analyzed retrospectively. A cohort of p16- patients (n = 30) from Gothenburg was included as a validation cohort.
Results:
Ninety-one per cent (n = 347) were p16+ and 9% (n = 33) p16-. Median follow-up was 33 months (range 4-78). p16- status was associated with higher age (≥65 years; p = 0.03), comorbidity (p = 0.03), male sex (p = 0.001) and perianal localization (p < 0.001). At 3 years progression free survival was 50% and 81% (p <0.0001) and OS 60% and 89% (p < 0.0001) for p16- and p16+ patients, respectively. Male sex, advanced T-stage (T3-4), N+ disease, advance treatment and p16- status were associated with inferior OS (p = 0.01 - p < 0.0001). In the p16- subgroup, advanced T-stage and intensive treatment were negative prognostic factors for OS (p = 0.007 and 0.009, respectively) but no clinical characteristic predicted persistent disease. The p16- validation cohort essentially confirmed the findings from the main cohort.
Interpretation:
p16- ASCC is a disease subset with specific clinical features and poor prognosis in need of improved treatment.
