Tumors of the anal canal
2026-05-13 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Keywords
Anal cancer ,human papillomavirus (HPV),. squamous intraepithelial lesion, anal squamous cell carcinoma, anal adenocarcinoma omaClassification
Definition
Anal cancer is a rare cancer in gastrointestinal tract malignancies, with human papillomavirus (HPV) infection and immunosuppression been major risk factors. 1 The pathology of the anal region is different from that of the perianal region and include epithelial tumors, precursor lesions (e.g. squamous intraepithelial lesion (SIL) and Paget disease, and tumor-like lesions, e.g. typically polyps as inflammatory cloacogenic polyp, driven by chronic mechanical stress (mucosal prolapse/straining) rather than inherited genetic mutations . 2,3
Squamous cell carcinoma is the most common malignancy. Adenocarcinoma is also common in the anal canal, especially in Asian populations. 4,5
| Tumors of the anal canal | Genetic events |
|---|---|
| Benign epithelial tumors and precursors | |
| Anal squamous intraepithelial neoplasia | Anal squamous intraepithelial lesions (SILs) are HPV-associated non-invasive neoplasms. Low-risk lesions e.g. classic condyloma and giant condyloma do not progress to high-risk lesions in most instances , and are linked to HPV6 and HPV11 subtypes, 6 whereas the risk of progression from a high-risk lesion to squamous cell carcinoma SERPINB3 is influenced most commonly by HPV16 and HPV18 subtypes. 7 |
| Malignant epithelial tumors | |
| Anal squamous cell carcinoma | Squamous cell carcinoma (SCC ) is the most common malignancy among anal cancers. 8 Anal infection with HPV, in particular HPV16 and HPV18, is the most important risk factor in the development of anal SCC . 9,10 |
| Recurrent alterations of the PI3K/AKT/mTOR pathway are frequent in these tumors: PIK3CA is the most frequent mutated and amplificated gene, followed by FBXW7 , FAT1 , PTEN, MYC, KMT2D, and SOX2 , among others with concurrent copy number variations, with frequently gains of chromosome 3q , affecting PIK3CA and losses of chromosome 11q, affecting ATM. 11-13 HPV-negaive tumors have a distinctly different genomic profile compared to their HPV-positive counterparts, with an increased prevalence TP53 and CDKN2A. 13 | |
| Anal adenocarcinoma | Primary anal adenocarcinoma (AA) is rare, but it is considered more agressive than anal squamous cell carcinoma. HPV infection has been implicated in a subset of anal canal adenocarcinomas, mainly HPV16, and,less commonly, followed by HPV18. 14 So far molecular data are limited. A single study of AA identified frequently KRAS mutations , less commonly PIK3CA , NRAS and BRAF . 14 A recent investigation in advanced anal adenocarcinoma reported frequent alteration as TP53, KRAS, ERBB3 , MYC and SMAD4 . 15 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 36975459 | 2023 | Anal Cancer: The Past, Present and Future. | Gondal TA et al |
| 2 | 31507349 | 2019 | Premalignant and Malignant Perianal Lesions. | Abbass MA et al |
| 3 | 32402305 | 2020 | Anal Cancer. | Young AN et al |
| 4 | 24659650 | 2014 | Malignancies of the anal canal: a multi-center retrospective analysis in South China population. | Sun P et al |
| 5 | 35274487 | 2022 | Characteristics of anal canal cancer in Japan. | Yamada K et al |
| 6 | 35562936 | 2022 | The Pathogenesis of Giant Condyloma Acuminatum (Buschke-Lowenstein Tumor): An Overview. | Purzycka-Bohdan D et al |
| 7 | 20730855 | 2010 | Human papillomavirus infection and anal dysplasia in renal transplant recipients. | Patel HS et al |
| 8 | 37439541 | 2023 | Anal Cancer and Anal Cancer Screening. | Cohen CM et al |
| 9 | 22379406 | 2011 | Neoplasms of anal canal and perianal skin. | Leonard D et al |
| 10 | 38760499 | 2024 | Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination. | Malagón T et al |
| 11 | 29416628 | 2018 | Exome sequencing reveals aberrant signalling pathways as hallmark of treatment-naive anal squamous cell carcinoma. | Cacheux W et al |
| 12 | 29804324 | 2018 | Array comparative genomic hybridization identifies high level of PI3K/Akt/mTOR pathway alterations in anal cancer recurrences. | Cacheux W et al |
| 13 | 40360682 | 2025 | Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer. | Rödel F et al |
| 14 | 29700411 | 2018 | A dualistic model of primary anal canal adenocarcinoma with distinct cellular origins, etiologies, inflammatory microenvironments and mutational signatures: implications for personalised medicine. | Herfs M et al |
| 15 | 41538763 | 2026 | Comprehensive Genomic Profiling of Advanced Anal Adenocarcinoma in Japan. | Ogura N et al |
Citation
Paola Dal Cin, PhD
Tumors of the anal canal
Atlas Genet Cytogenet Oncol Haematol. 2026-05-13
Online version: http://atlasgeneticsoncology.org/solid-tumor/209373
