Download PDF
Clin Colon Rectal Surg
DOI: 10.1055/s-0045-1809708
Review Article

Anal Dysplasia: Epidemiology, Risk Factors, and Progression to Malignancy

Megan Boyer
1   Department of Surgery, University of Rochester Medical Center, Rochester, New York
,
Zhaomin Xu
1   Department of Surgery, University of Rochester Medical Center, Rochester, New York
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

This review aims to address the framework for classification of anal dysplasia, immunogenic and behavioral risk factors for development of disease, the progression to anal cancer, and key intervention points to guide contemporary practice. Although anal cancer is rare, its rising incidence and disproportionate impact on racial minorities, immunocompromised individuals, and older adults require attention to combat high disease burden within these communities. Concentrated efforts with targeted resource allocation are required to address this rising disease incidence, following new screening guidelines developed to identify groups that are considered high-risk for anal dysplasia and the development of anal squamous cell carcinoma.

Keywords

anal dysplasia - anal cancer - anal squamous cell carcinoma - human papillomavirus


Publication History

Article published online:
23 June 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 ASCRS. Anal Cancer Expanded Version. Accessed June 6, 2025 at: https://fascrs.org/patients/diseases-and-conditions/a-z/anal-cancer-expanded-version
    PubMed
  • 2 Johnson LG, Madeleine MM, Newcomer LM, Schwartz SM, Daling JR. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 2004; 101 (02) 281-288
    PubMedSearch in Google Scholar
  • 3 Nelson VM, Benson III AB. Epidemiology of anal canal cancer. Surg Oncol Clin N Am 2017; 26 (01) 9-15
    PubMedSearch in Google Scholar
  • 4 Krzowska-Firych J, Lucas G, Lucas C, Lucas N, Pietrzyk Ł. An overview of human papillomavirus (HPV) as an etiological factor of the anal cancer. J Infect Public Health 2019; 12 (01) 1-6
    CrossrefPubMedSearch in Google Scholar
  • 5 Williamson A-L. Recent developments in human papillomavirus (HPV) vaccinology. Viruses 2023; 15 (07) 1440
    PubMedSearch in Google Scholar
  • 6 Nelson CW, Mirabello L. Human papillomavirus genomics: Understanding carcinogenicity. Tumour Virus Res 2023; 15: 200258
    PubMedSearch in Google Scholar
  • 7 Bernard H-U, Burk RD, Chen Z, van Doorslaer K, zur Hausen H, de Villiers EM. Classification of papillomaviruses (PVs) based on 189 PV types and proposal of taxonomic amendments. Virology 2010; 401 (01) 70-79
    PubMedSearch in Google Scholar
  • 8 Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev 2003; 16 (01) 1-17
    CrossrefPubMedSearch in Google Scholar
  • 9 CDC. Human Papillomavirus (HPV) Infection. STI Treatment Guidelines, 2021. Accessed June 6, 2025 at: https://www.cdc.gov/std/treatment-guidelines/anogenital-warts.htm
    PubMed
  • 10 Satterwhite CL, Torrone E, Meites E. et al. Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. Sex Transm Dis 2013; 40 (03) 187-193
    PubMedSearch in Google Scholar
  • 11 CDC. Human Papillomavirus (HPV). About HPV. 2024. Accessed June 6, 2025 at: https://www.cdc.gov/hpv/about/index.html
    PubMed
  • 12 Dunne EF, Unger ER, Sternberg M. et al. Prevalence of HPV infection among females in the United States. JAMA 2007; 297 (08) 813-819
    PubMedSearch in Google Scholar
  • 13 Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010; 202 (12) 1789-1799
    CrossrefPubMedSearch in Google Scholar
  • 14 Gargano JW, Unger ER, Liu G. et al. Prevalence of genital human papillomavirus in males, United States, 2013-2014. J Infect Dis 2017; 215 (07) 1070-1079
    PubMedSearch in Google Scholar
  • 15 Adebamowo SN, Famooto A, Dareng EO. et al. Clearance of type-specific, low-risk, and high-risk cervical human papillomavirus infections in HIV-negative and HIV-positive women. J Glob Oncol 2018; 4: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 16 Veldhuijzen NJ, Snijders PJ, Reiss P, Meijer CJ, van de Wijgert JH. Factors affecting transmission of mucosal human papillomavirus. Lancet Infect Dis 2010; 10 (12) 862-874
    PubMedSearch in Google Scholar
  • 17 Bulkmans NWJ, Berkhof J, Bulk S. et al.; POBASCAM Study Group. High-risk HPV type-specific clearance rates in cervical screening. Br J Cancer 2007; 96 (09) 1419-1424
    PubMedSearch in Google Scholar
  • 18 de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health 2020; 8: E180-E190 . Accessed June 6, 2025 at: https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(19)30488-7/fulltext
    PubMedSearch in Google Scholar
  • 19 Lewis RM, Laprise, JF, Gargano, JW. et al. Estimated prevalence and incidence of disease-associated HPV types among 15–59-year-olds in the United States. Sex Transm Dis 2021; 48: 273-277
    PubMedSearch in Google Scholar
  • 20 Van Dyne EA, Henley SJ, Saraiya M, Thomas CC, Markowitz LE, Benard VB. Trends in human papillomavirus-associated cancers - United States, 1999-2015. MMWR Morb Mortal Wkly Rep 2018; 67 (33) 918-924
    CrossrefPubMedSearch in Google Scholar
  • 21 CDC. Cancer. Cancers Linked with HPV Each Year. 2024. Accessed June 6, 2025 at: https://www.cdc.gov/cancer/hpv/cases.html
    PubMed
  • 22 Elorza G, Saralegui Y, Enríquez-Navascués JM, Placer C, Velaz L. Anal intraepitelial neoplasia: A narrative review. Rev Esp Enferm Dig 2016; 108 (01) 31-39
    PubMedSearch in Google Scholar
  • 23 Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S. Anal cancer: The past, present and future. Curr Oncol 2023; 30 (03) 3232-3250
    PubMedSearch in Google Scholar
  • 24 Albuquerque A, Stirrup O, Nathan M, Clifford GM. Burden of anal squamous cell carcinoma, squamous intraepithelial lesions and HPV16 infection in solid organ transplant recipients: A systematic review and meta-analysis. Am J Transplant 2020; 20 (12) 3520-3528
    PubMedSearch in Google Scholar
  • 25 Keller K, Ramos-Cartagena JM, Guiot HM. et al. Association of smoking with anal high-risk HPV infection and histologically confirmed anal high-grade squamous intraepithelial lesions among a clinic-based population in Puerto Rico. Cancer Treat Res Commun 2022; 30: 100503
    PubMedSearch in Google Scholar
  • 26 Frisch M, Glimelius B, Wohlfahrt J, Adami H-O, Melbye M. Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism?. J Natl Cancer Inst 1999; 91 (08) 708-715
    PubMedSearch in Google Scholar
  • 27 Hernandez AL, Efird JT, Holly EA, Berry JM, Jay N, Palefsky JM. Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM. AIDS 2014; 28 (09) 1341-1349
    PubMedSearch in Google Scholar
  • 28 Weis SE, Vecino I, Pogoda JM. et al. Prevalence of anal intraepithelial neoplasia defined by anal cytology screening and high-resolution anoscopy in a primary care population of HIV-infected men and women. Dis Colon Rectum 2011; 54 (04) 433-441
    PubMedSearch in Google Scholar
  • 29 Cohen CM, Clarke MA. Anal cancer and anal cancer screening. Clin Obstet Gynecol 2023; 66 (03) 516-533
    PubMedSearch in Google Scholar
  • 30 Darragh TM, Colgan TJ, Cox JT. et al.; Members of LAST Project Work Groups. The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and consensus recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology. Arch Pathol Lab Med 2012; 136 (10) 1266-1297
    CrossrefPubMedSearch in Google Scholar
  • 31 Stoler MH, Schiffman M. Atypical Squamous Cells of Undetermined Significance-Low-grade Squamous Intraepithelial Lesion Triage Study (ALTS) Group. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001; 285 (11) 1500-1505
    CrossrefPubMedSearch in Google Scholar
  • 32 Machalek DA, Poynten M, Jin F. et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol 2012; 13 (05) 487-500
    CrossrefPubMedSearch in Google Scholar
  • 33 NIH. Cancer Stat Facts: Anal Cancer. Cancer of the Anus, Anal Canal, and Anorectum. SEER. Accessed June 6, 2025 at: https://seer.cancer.gov/statfacts/html/anus.html
    PubMed
  • 34 Hotca A, Goodman KA. Trends in anal cancer: Leveraging public health efforts to improve cancer care. J Clin Oncol 2023; 41 (06) 1180-1182
    PubMedSearch in Google Scholar
  • 35 Damgacioglu H, Lin YY, Ortiz AP. et al. State variation in squamous cell carcinoma of the anus incidence and mortality, and association with HIV/AIDS and smoking in the United States. J Clin Oncol 2023; 41 (06) 1228-1238
    PubMedSearch in Google Scholar
  • 36 Nelson RA, Levine AM, Bernstein L, Smith DD, Lai LL. Changing patterns of anal canal carcinoma in the United States. J Clin Oncol 2013; 31 (12) 1569-1575
    PubMedSearch in Google Scholar
  • 37 Cruz A, Chen D, Hsu P. et al. Racial and gender disparities in the incidence of anal cancer: analysis of the Nationwide Inpatient Sample (NIS). J Gastrointest Oncol 2019; 10 (01) 37-41
    PubMedSearch in Google Scholar
  • 38 CDC. HIV. Fast Facts: HIV in the US by Race and Ethnicity. 2024. Accessed June 6, 2025 at: https://www.cdc.gov/hiv/data-research/facts-stats/race-ethnicity.html
    PubMed
  • 39 Tong WW, Hillman RJ, Kelleher AD, Grulich AE, Carr A. Anal intraepithelial neoplasia and squamous cell carcinoma in HIV-infected adults. HIV Med 2014; 15 (02) 65-76
    PubMedSearch in Google Scholar
  • 40 Hoots BE, Palefsky JM, Pimenta JM, Smith JS. Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions. Int J Cancer 2009; 124 (10) 2375-2383
    PubMedSearch in Google Scholar
  • 41 CDC. Vaccines & Immunizations. HPV Vaccination Recommendations. 2023. Accessed June 6, 2024 at: https://www.cdc.gov/vaccines/vpd/hpv/hcp/recommendations.html
    PubMed
  • 42 Berenson AB, Guo F, Chang M. Association of human papillomavirus vaccination with the incidence of squamous cell carcinomas of the anus in the US. JAMA Oncol 2022; 8 (04) 1-3
    PubMedSearch in Google Scholar
  • 43 Villarroel MA, Galinksy AM, Lu P-J, Pingali C. Human papillomavirus vaccination coverage in children ages 9–17 years: United States, 2022. NCHS Data Brief 2024; (495) 1-8
    PubMedSearch in Google Scholar
  • 44 New York State Department of Health Aids Institute ǀ Clinical Guidelines Program. Prevention and Management of Human Papillomavirus Infection in Adults With HIV. Accessed June 6, 2025 at: https://www.hivguidelines.org/guideline/hiv-hpv/
    PubMed
  • 45 Marcus JL, Hurley LB, Hare CB. et al. Preexposure prophylaxis for HIV prevention in a large integrated health care system: Adherence, renal safety, and discontinuation. J Acquir Immune Defic Syndr 2016; 73 (05) 540-546
    PubMedSearch in Google Scholar
  • 46 McCormack S, Dunn DT, Desai M. et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial. Lancet 2016; 387 (10013): 53-60
    PubMedSearch in Google Scholar
  • 47 Choopanya K, Martin M, Suntharasamai P. et al.; Bangkok Tenofovir Study Group. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013; 381 (9883): 2083-2090
    PubMedSearch in Google Scholar
  • 48 Clinical Guidelines Program. PEP to Prevent HIV Infection. May 14, 2025. Accessed June 6, 2025 at: https://www.hivguidelines.org/guideline/hiv-pep/
    PubMed
  • 49 Stier EA, Clarke MA, Deshmukh AA. et al. International Anal Neoplasia Society's consensus guidelines for anal cancer screening. Int J Cancer 2024; 154 (10) 1694-1702
    CrossrefPubMedSearch in Google Scholar
  • 50 Clarke MA, Deshmukh AA, Suk R. et al. A systematic review and meta-analysis of cytology and HPV-related biomarkers for anal cancer screening among different risk groups. Int J Cancer 2022; 151: 1889-1901 . Wiley Online Library. Accessed June 6, 2025 at: https://onlinelibrary.wiley.com/doi/10.1002/ijc.34199
    PubMedSearch in Google Scholar
  • 51 Jay N. High-resolution anoscopy: Procedure and findings. Semin Colon Rectal Surg 2017; 28: 75-80
    PubMedSearch in Google Scholar
  • 52 Palefsky JM, Lee JY, Jay N. et al.; ANCHOR Investigators Group. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med 2022; 386 (24) 2273-2282
    CrossrefPubMedSearch in Google Scholar