Current guidelines for anal HPV-related disease screening
There is no consensus in national and international guidelines regarding anal HPV-related disease screening. Recommendations can be conflicting and with low strength of evidence (expert opinion in many cases).
First, we should differentiate between anal cancer screening and screening for anal high-grade squamous intraepithelial lesions (HSIL), as recommendations for these might differ. Anal cancer screening consists of inquiring about anal symptoms, visual inspection and digital anorectal examination (DARE), with the objective of diagnosing cancer in early stages.1 Several guidelines recommend anal cancer screening (Table 1), with variable periodicity (commonly repeating it annually). Most of the guidelines do not specify the age of starting or stopping screening. On the other hand, screening for anal HSIL consists of performing anal cytology, followed by high-resolution anoscopy (HRA) if the cytology is abnormal, with the objective of diagnosing HSIL through HRA-guided biopsy.2,3 Regarding anal HSIL screening, there are divergent recommendations summarized in Table 1. These can be conditioned by sexual practices, concomitant diseases and/or medications, age or the presence of other HPV-related diseases. All guidelines coincide that cytology should not be done if there is no option of performing HRA if the cytology is abnormal.

The prevalence of anal cancer in the general population is low, and does not justify routine screening. This is reflected in guidelines issued by “general” societies (Colorectal Surgeons, Medical/Surgical Oncology, etc). However, the prevalence of anal cancer is much higher in specific populations and the recommendations in guidelines focusing on these high-risk individuals must be reviewed. These primarily include people living with HIV (PLWH), with the highest risk in men who have sex with men (MSM), followed by heterosexual men/women living with HIV, women with genital HPV-related dysplasia/cancer and men/women with genital warts. In recent years, other high-risk populations have been considered, including transplant recipients receiving immunosuppressive medication, but with low quality of evidence.3
A major caveat is that some of these guidelines were published many years ago (some more than a decade ago). For example, one of the pioneer guidelines regarding anal HSIL screening, the New York State Department of Health AIDS Institute, has just recently updated its recommendations in March 2020, the previous version being from 2007. However, guidelines revised on a yearly basis (national/international HIV guidelines) review all aspects of HIV clinical management but usually provide only generic recommendations regarding cancer screening in PLWH.
There are several aspects that explain the lack of consensus between guidelines. The low grade of evidence makes it difficult to establish screening programs, which in turn makes it difficult to generate solid data to increase the level of evidence, generating a vicious circle. We need data confirming that anal HSIL screening and treatment has an impact reducing anal cancer, and the Anal Cancer/HSIL Outcomes Research (ANCHOR) study will be crucial in this aspect. We also need cost-effectiveness studies to justify implementing screening programs, and these studies will need to be country-specific.
Finally, other guidelines to consider are the International Anal Neoplasia Society (IANS) guidelines for practice standards in the detection of anal cancer precursors and for the practice of digital anal rectal examination.4,5 These guidelines give recommendations on how to adequately perform DARE; the minimum standards for performance of DARE, anal cytology and HRA; and the minimum competencies anoscopists should have and how to evaluate them.
DISCLOSURE AC has received from Merck Sharp & Dome financial support for research/ educational and advisory activities.
References
1. Ong J, Chen M, Grulich AE, Fairley CK. Regional and national guideline recommendations for digital ano-rectal examination as a means for anal cancer screening in HIV positive men who have sex with men: a systematic review. BMC Cancer 2014; 14: 557. Available from: https://pubmed.ncbi.nlm.nih.gov/25081485/
2. Leeds IR, Fang SH. Anal Cancer and Intraepithelial Neoplasia Screening: A Review. World J Gastrointest Surg 2016; 8(1): 41-51. Available from: https://pubmed.ncbi.nlm.nih.gov/26843912/
3. Albuquerque A, Rios E, Schmitt F. Recommendations Favoring Anal Cytology as a Method for Anal Cancer Screening: A Systematic Review. Cancers 2019; 11: 1942. Available from: https://pubmed.ncbi.nlm.nih.gov/31817212/
4. Hillman RJ, Cuming T, Darragh T, et al. 2016 IANS International Guidelines for Practice Standards in the Detection of Anal Cancer Precursors. J Low Genit Tract Dis. 2016; 20(4):283-91. Available from: https://pubmed.ncbi.nlm.nih.gov/27561134/
5. Hillman RJ, Berry-Lawhorn JM, Ong JJ, et al. International Anal Neoplasia Society Guidelines for the Practice of Digital Anal Rectal Examination. J Low Genit Tract Dis. 2019; 23(2):138-146. Available from: https://pubmed.ncbi.nlm.nih.gov/30907777/
6. NYSDHAI: New York State Department of Health AIDS Institute. Anal dysplasia and cancer, March 2020. Available from: https://www.hivguidelines.org/hiv-care/anal-dysplasia-cancer/ Last accessed: 25th January 2021.
7. HIVMA/IDSA: HIV Medicine Association of the Infectious Diseases Society of America. Thompson MA, Horberg MA, Agwu AL et al. Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2020 Nov 6:ciaa1391. Available from: https://pubmed.ncbi.nlm.nih.gov/33225349/
8. DHHS: Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. Available from: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportunistic-infection/human-papillomavirus-disease?view=full Last accessed: 25th January 2021.
9. EACS: European AIDS Clinical Society. GUIDELINES Version 10.1 October 2020. Available from: https://www.eacsociety.org/files/guidelines-10.1_finaljan2021_1.pdf Last accessed: 25th January 2021.
10. GeSIDA: Grupo de Estudio del SIDA-SEIMC. Guía de práctica clínica sobre los tumores no definitorios de sida e infección por el VIH (Actualización Marzo 2019). Available from: http://gesida-seimc.org/wp-content/uploads/2019/05/gesida_DC_TumoresNoDefinitorios_Marzo_2019_14_05_19.pdf Last accessed: 21st February 2021.
11. BHIVA: British HIV Association. Bower M, Palfreeman A, Alfa-Wali M, et al. British HIV Association guidelines for HIV-associated malignancies 2014. HIV Med. 2014; 15 Suppl 2:1–92. Available from: https://pubmed.ncbi.nlm.nih.gov/24528810/
Anal cancer recommendations from: Fakoya A, Lamba H, Mackie N et al. British HIV Association, BASHH and FSRH guidelines for the management of the sexual and reproductive health of people living with HIV infection 2008. HIV Medicine 2008; 9:681-720. Available from: https://pubmed.ncbi.nlm.nih.gov/18983476/
12. DAIG: German AIDS Society. Esser S, Kreuter A, Oette M, et al. German-Austrian guidelines on anal dysplasia and anal cancer in HIV-positive individuals: Prevention, diagnosis, and treatment. J Dtsch Dermatol Ges 2015; 13 (12): 1302–1319. Available from: https://pubmed.ncbi.nlm.nih.gov/26612810/
13. ASCRS: The American Society of Colon and Rectal Surgeons. Stewart DB, Gaertner WB, Glasgow SC et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Anal Squamous Cell Cancers (Revised 2018). Dis Colon Rectum 2018; 61 (7): 755–774. Available from: https://pubmed.ncbi.nlm.nih.gov/29878949/
14. ASTIDCP: American Society of Transplantation Infectious Diseases Community of Practice. Chin-Hong PV, Reid GE. Human papillomavirus infection in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33 (9): e13590. Available from: hhttps://pubmed.ncbi.nlm.nih.gov/31077438/
OTHER ARTICLES INCLUDED IN THE HPW SPECIAL ISSUE ON ANAL CANCER

J Palefsky. Screening for anal high-grade squamous intraepithelial lesions and anal cancer- has its time come?
CJ Wang. Treatment for anal cancer
EA Stier. Anal HPV infection: risk groups and natural history
JP Terlizzi, SE Goldstone. Treatment for anal high grade squamous intraepithelial lesions
J Kauffmann. The modern anal neoplasia clinic
C Brickman. Cytology and HPV testing for anal HSIL screening
GB Ellsworth, TJ Wilkin. Early HPV vaccination could reduce anal cancer incidence
TM Darragh. Pathology of anal squamous intraepithelial lesions and cancer: similarities and differences from cervical pathology
JM Berry-Lawhorn. Groups at high risk of anal cancer
RJ Hillman. Digital anal rectal examination (DARE) for anal cancer prevention
N Jay. Practising and training for high resolution anoscopy