Multicentre Investigation of Prognostic Factors Incorporating p16 and Tumour Infiltrating Lymphocytes for Anal Cancer After Chemoradiotherapy

Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We i...

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Veröffentlicht in:Clinical oncology (Royal College of Radiologists (Great Britain)) 2021-10, Vol.33 (10), p.638-649
Hauptverfasser: Wakeham, K., Murray, L., Muirhead, R., Hawkins, M.A., Sebag-Montefiore, D., Brown, S., Murphy, L., Thomas, G., Bell, S., Whibley, M., Morgan, C., Sleigh, K., Gilbert, D.C.
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Sprache:eng
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Zusammenfassung:Anal squamous cell carcinomas (ASCC) are strongly associated with human papillomaviruses. Standard of care is chemoradiotherapy at uniform doses with no treatment stratification. Immunohistochemical staining for p16INK4A (p16), a surrogate for human papillomaviruses, is prognostic for outcomes. We investigated this alongside clinical-pathological factors, including tumour infiltrating lymphocyte (TIL) scores. Using an independent, multicentre cohort of 257 ASCC treated with chemoradiotherapy, pretreatment biopsies were stained and scored for p16 and TIL. Kaplan–Meier curves were derived for outcomes (disease-free survival [DFS], overall survival and cancer-specific survival), by stage, p16 and TIL scores and Log-rank tests were carried out to investigate prognostic effect. A multivariate analysis was carried out using Cox regression. Stage, sex, p16 and TILs were independently prognostic. Hazard ratios for death (overall survival) were 2.51 (95% confidence interval 1.36–4.63) for p16 negative versus p16 positive, 2.17 (1.34–3.5) for T3/4 versus T1/2, 2.42 (1.52–3.8) for males versus females and 3.30 (1.52–7.14) for TIL1 versus TIL3 (all P < 0.05). We have refined prognostic factors in ASCC. p16 adds to stratification by stage with respect to DFS in early disease and overall survival/DFS in locally advanced cancers. Our data support the role of the host immune response in mediating outcomes. These factors will be prospectively evaluated in PLATO (ISRCTN88455282). •Large independent multicentre cohort of patients with anal cancer treated with chemoradiotherapy.•Consistent and independent prognostic effect of p16 and tumour infiltrating lymphocytes demonstrated.•Potential clinical utility in stratifying future treatments in locally advanced disease.
ISSN:0936-6555
1433-2981
DOI:10.1016/j.clon.2021.04.015