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. 2025 May 7:64:633-640.
doi: 10.2340/1651-226X.2025.42498.

Clinical characteristics and treatment outcome in p16 negative anal cancer

Catherine Burgos  1 , Calin Radu  2 , Sofia Heyman  3 , Nina Cavalli-Björkman  2 , Peter Nygren  2
Affiliations

Clinical characteristics and treatment outcome in p16 negative anal cancer

Catherine Burgos et al. Acta Oncol. .

Abstract

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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Conflict of interest statement

The authors report there are no competing interests to declare.

Figures

Figure 1
Figure 1
Overall treatment outcome according to p16-status for the Uppsala cohort (n = 380). See Table 2, for details on outcome and statistical inference.
Figure 2
Figure 2
Overall survival according to p16-status with p16- patients separated for treatment center, Gothenburg cohort used as a validation cohort (a) and disease specific survival in Uppsala patients (b) and progression free survival (c) according to p16-status in Uppsala patients.
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