Clinical characteristics and treatment outcome in p16 negative anal cancer
DOI:
https://doi.org/10.2340/1651-226X.2025.42498Keywords:
Anal cell carcinoma, sqaumous cell carcinoma, p16, Anal carcinoma, anal cancinoma, anal cancer, Anal cancer biopsiesAbstract
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.
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