ArticleBritish journal of cancer2015
HPV-negative squamous cell carcinoma of the anal canal is unresponsive to standard treatment and frequently carries disruptive mutations in TP53.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 110 citations in OpenAlex.
- Trial
- Anal canal neoplasms in the modern era: integrating HPV biology, LAST terminology, and evolving molecular classification.Virchows Archiv : an international journal of pathology · 2026Review
- Deciphering the Molecular Landscape of Squamous Cell Carcinoma of the Anal Canal: From Biology to Precision Oncology.Cancers · 2026Review
- Advances in anal cancer treatment: current standards, the role of immunotherapy and emerging strategies.ESMO gastrointestinal oncology · 2026Review
- Predicting locoregional treatment failure in anal cancer using multivariable clinical-imaging models.Clinical and translational radiation oncology · 2026Article
- Outcomes after (chemo)radiotherapy for anal cancer - A nationwide cohort study.Clinical and translational radiation oncology · 2026Article
- Divergent immune ecosystems in HPV-associated and HPV-independent lower anogenital tract malignancies.Frontiers in immunology · 2026Review
- A Case of a Longstanding Perianal Lesion Presenting as Advanced Squamous Cell Carcinoma of the Anus.Cureus · 2025Article
- Cerebral metastasis from anal squamous cell carcinoma: A case report and literature review.Oncology letters · 2025Article
- Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer.Nature reviews. Clinical oncology · 2025Review
- Clinical characteristics and treatment outcome in p16 negative anal cancer.Acta oncologica (Stockholm, Sweden) · 2025Article
- Clinical outcomes and prognostic factors of concurrent chemoradiotherapy for anal squamous cell carcinoma in Japan.International journal of clinical oncology · 2024Article
- HPV status and immunohistochemical analysis of p16, p53 and PD‑L1 expression as prognostic biomarkers in patients with squamous cell anal cancer receiving definitive radiotherapy/chemoradiotherapy.Oncology letters · 2024Article
- A study of microRNAs as new prognostic biomarkers in anal cancer patients.Acta oncologica (Stockholm, Sweden) · 2024Article
- Unveiling the Role of Human Papillomavirus in Urogenital Carcinogenesis a Comprehensive Review.Viruses · 2024Review
- The Causes and Consequences of DNA Damage and Chromosomal Instability Induced by Human Papillomavirus.Cancers · 2024Review
- Human Papillomavirus-Induced Chromosomal Instability and Aneuploidy in Squamous Cell Cancers.Viruses · 2024Review
- Unraveling Emerging Anal Cancer Clinical Biomarkers from Current Immuno-Oncogenomics Advances.Molecular diagnosis & therapy · 2024Review
- Recent Advances in the Management of Anal Cancer.Healthcare (Basel, Switzerland) · 2023Review
- Anal Cancer: The Past, Present and Future.Current oncology (Toronto, Ont.) · 2023Review
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established. The objective of this study was to determine the prognostic significance of tumour HPV status, p16 and p53 expression, and mutations in TP53 in patients with SCCAC receiving (chemo)radiotherapy.
methodsHuman papillomavirus DNA was determined using an INNO-LiPA-based assay in tumour tissue of 107 patients with locally advanced SCCAC. Patients were treated with radiotherapy, with or without concurrent chemotherapy consisting of a fluoropyrimidine and mitomycin C. Expression of p16 and p53 was determined using immunohistochemistry. Exons 2-11 of TP53 in tumour tissue were sequenced.
resultsDNA of high-risk HPV types was detected in 93 out of 107 tumours (87%), all of which overexpressed p16 (HPV+/p16+). Of 14 HPV-negative (HPV-) tumours (13%), 10 (9%) were p16-negative (HPV-/p16-) and 4 (4%) overexpressed p16 (HPV-/p16+). Patients with HPV-/p16- disease had inferior 3-year locoregional control (LRC) (15%) compared with patients with HPV+/p16+ tumours (82%, P<0.001) and HPV-/p16+ tumours (75%, P=0.078). Similarly, 3-year overall survival (OS) was 35% (HPV-/p16-) vs 87% (HPV+/p16+, P<0.001) and 75% (HPV-/p16+, P=0.219). Disruptive mutations in TP53 were found in 80% of HPV-/p16- tumours vs 6% of HPV+/p16+ tumours (P<0.001). In multivariate analysis, HPV-/p16- status was an independent predictor of inferior LRC and OS.
conclusionsHPV- tumours are frequently TP53 mutated. HPV-/p16- status is a strong predictor for reduced LRC and OS, and alternative treatment strategies for patients with HPV-/p16- disease need to be explored.
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