Skip to main content

Advertisement

SpringerLink
Log in

The Diagnostic and Therapeutic Challenge of Anal Intraepithelial Neoplasia

  • Large Intestine (B Cash, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

No single modality of care serves as the defined best practice for the treatment of anal intraepithelial neoplasia (AIN). This review aims to present the common treatment modalities germane to AIN while considering evolving evidence.

Recent Findings

AIN affords an opportunity to evaluate and treat patients before the development of invasive diseases. Efforts to screen for AIN have yielded mixed results. The major available pharmacotheraputic and surgical options offer efficacious options to reduce the bioburden of disease but can be met with high levels of recurrent disease. None affords a predictably durable response in severe disease.

Summary

Vaccination as primary prevention will likely reduce the overall upward trend in AIN. Evidence suggests vaccination also affords improvement in recurrent disease. Early evidence reveals potential benefit in multimodal approaches to control AIN. Valuable data is anticipated from the phase III, randomized ANCHOR study evaluating the management of high-grade AIN in HIV +patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007;90:1–636.

    PubMed Central  Google Scholar 

  2. McCance DJ, Clarkson PK, Dyson JL, Walker PG, Singer A. Human papillomavirus types 6 and 16 in multifocal intraepithelial neoplasia of the female lower genital tract. Br J Obstet Gynaecol. 1985;92:1093–100.

    Article  PubMed  CAS  Google Scholar 

  3. •• Garland SM. Human papillomavirus update with a particular focus on cervical disease. Pathology. 2002;34(3):213–24. (75% of the sexually active pop has been exposed and 15–20% carries the virus).

    Article  PubMed  Google Scholar 

  4. • Weinstock H, Berman S, Cates W Jr. Sexually transmitted diseases among American youth: incidence and prevalence estimates, 2000. Perspect Sex Reprod Health. 2004;36(1):6–10. (1% of sexually active adults have genital warts).

    Article  PubMed  Google Scholar 

  5. Centers for Disease Control and Prevention. 2017. Genital HPV infection-fact sheet. Available at: http://www.cdc.gov/hpv/parents/questions-answers.html. Accessed 12, 2017.

  6. Meites E, Kemp A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination – updated recommendations of the advisory committee on immunization practices. MMWR Morb Mortal Wkly Rep. 2016;65:1405–8.

    Article  PubMed  Google Scholar 

  7. •• Wiley DJ, Douglas J, Beutner K. External genital warts: diagnosis, treatment, and prevention. Clin Infect Dis. 2002;35(suppl. 2):S210–24. (serotypes / high risk and low risk p.6 cochrane).

    Article  PubMed  CAS  Google Scholar 

  8. Shvetsov YB, Hernandez BY, McDuffie K, Wilkens LR, Zhu X, Ning L, et al. Duration and Clearance of Anal Human Papillomavirus (HPV) Infection among Women: The Hawaii HPV Cohort Study. Clin Infect Dis. 2009;48(5):536–46.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Poggio JL. Premalignant lesions of the anal canal and squamous cell carcinoma of the anal canal. Clin Colon Rectal Surg. 2011;24:177–92.

    Article  PubMed  PubMed Central  Google Scholar 

  10. American Cancer Society. Cancer Facts & Figures 2017. Atlanta, GA: American Cancer Society; 2017. Available at https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017. Accessed 10 Nov 2017.

  11. American Cancer Society. Cancer Facts & Figures 2010. Atlanta, GA: American Cancer Society; 2010. Available at https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017. Accessed 10 Nov 2017.

  12. Nayar R, Wilbur D. The Bethesda system for reporting cervical cytology. 3rd ed. New York: McGraw-Hill; 2015.

    Google Scholar 

  13. • Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD. Standards Practice Task Force of the American Society of Colon and Rectal Surgeons. Practice parameters for anal squamous neoplasms. Dis Colon Rectum. 2012;55(7):735–49. A comprehensive evidence-based review compiled and updated by ASCRS, designed to guide the practice of surgeons treating anal squamous neoplasms.

    Article  PubMed  Google Scholar 

  14. Palefsky JM, Holly EA, Hogeboom CJ, Berry JM, Jay N, Darragh TM. Anal cytology as a screening tool for anal squamous intraepithelial lesions. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14(5):415–22.

    Article  PubMed  CAS  Google Scholar 

  15. Panther LA, Wagner K, Proper J, Fugelso DK, Chatis PA, Weeden W, et al. High resolution anoscopy findings for men who have sex with men: inaccuracy of anal cytology as a predictor of histologic high-grade anal intraepithelial neoplasia and the impact of HIV serostatus. Clin Infect Dis. 2004;38(10):1490–2.

    Article  PubMed  Google Scholar 

  16. Jin F, Grulich AE, Poynten IM, Hillman RJ, Templeton DJ, Law CL, et al. The performance of anal cytology as a screening test for anal HSILs in homosexual men. Cancer Cytopathol. 2016;124(6):415–24.

    Article  PubMed  Google Scholar 

  17. Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: a review of diagnosis and management. World J Gastrointest Oncol. 2017;9(2):50–61.

    Article  PubMed  PubMed Central  Google Scholar 

  18. • Richel O, Hallensleben ND, Kreuter A, van Noesel CJ, Prins JM, de Vries HJ. High-resolution anoscopy: clinical features of anal intraepithelial neoplasia in HIV-positive men. Dis Colon Rectum. 2013;56(11):1237–42. Good paper describing high risk lesions seen with HRA, helpful color pictures.

    Article  PubMed  Google Scholar 

  19. Crawshaw BP, Russ AJ, Stein SL, Reynolds HL, Marderstein EL, Delaney CP, et al. High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference? Dis Colon Rectum. 2015;58(1):53–9.

    Article  PubMed  Google Scholar 

  20. Grillo-Ardila CF, Angel-Müller E, Salazar-Díaz LC, Gaitán HG, Ruiz-Parra AI, Lethaby A. Imiquimod for anogenital warts in non-immunocompromised adults. Cochrane Database Syst Rev. 2014;(11):CD010389. https://doi.org/10.1002/14651858.CD010389.pub2.

  21. Fox Paul A, Mayura N, Nicholas F, Naveena S, Justin W, Glen D, et al. A double-blind, randomized controlled trial of the use of imiquimod cream for the treatment of anal canal high-grade anal intraepithelial neoplasia in HIV-positive MSM on HAART, with long-term follow-up data including the use of open-label imiquimod. AIDS. 2010;24(15):2331e5.

    Google Scholar 

  22. Dockrell DH, Kinghorn GR. Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother. 2001;48(6):751–5.

    Article  PubMed  CAS  Google Scholar 

  23. Tatti S, Stockfleth E, Beutner KR, Tawfik H, Elsasser U, Weyrauch P, et al. Polyphenon E: a new treatment for external anogenital warts. Br J Dermatol. 2010;162:176–84.

    Article  PubMed  CAS  Google Scholar 

  24. Richel O, de Vries HJC, van Noesel CJM, Dijkgraaf MGW, Prins JM. Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. The Lancet Oncology. 2013;14(4):346–53.

    Article  PubMed  CAS  Google Scholar 

  25. Beutner KR, Spruance SL, Hougham AJ, Fox TL, Owens ML, Douglas JM Jr. Treatment of genital warts with an immune-response modifier (imiquimod). J Am Acad Dermatol. 1998;38:230–9.

    Article  PubMed  CAS  Google Scholar 

  26. Scholefield JH, Harris D, Radcliffe A. Guidelines for Management of Anal Intraepithelial Neoplasia. Color Dis. 2011;13:3–10.

    Article  Google Scholar 

  27. Schofer H, Tatti S, Lynde CW, Skerlev M, Hercogova J, Rotaru M, et al. Sinecatechins and imiquimod as proactive sequential therapy of external genital and perianal warts in adults. Int J STD AIDS. 2017;28:1433–43.

    Article  PubMed  CAS  Google Scholar 

  28. Scholefield JH, Castle MT, Watson NF. Malignant transformationof high-grade anal intraepithelial neoplasia. Br J Surg. 2005;92:1133–6.

    Article  PubMed  CAS  Google Scholar 

  29. Watson AJ, Smith BB, Whitehead MR, Sykes PH, Frizelle FA. Malignant progression of anal intra-epithelial neoplasia. ANZ J Surg. 2006;76:715–7.

    Article  PubMed  Google Scholar 

  30. •• Goldstone SE, Johnstone AA, Moshier EL. Long-term outcome of ablation of anal high-grade squamous intraepithelial lesions: recurrence and incidence of cancer. Dis Colon Rectum. 2014;57(3):316–23. Very large retrospective review showing the safety and efficacy of multiple ablative techniques.

    Article  PubMed  Google Scholar 

  31. Marks DK, Goldstone SE. Electrocautery ablation of high-grade anal squamous intraepithelial lesions in HIV-negative and HIV-positive men who have sex with men. J Acquir Immune Defic Syndr. 2012;59(3):259–65.

    Article  PubMed  Google Scholar 

  32. Burgos J, Curran A, Landolfi S, Navarro J, Tallada N, Guelar A, et al. The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men. HIV Med. 2016;17:524–31.

    Article  PubMed  CAS  Google Scholar 

  33. • Richel O, de Vries HJ, van Noesel CJ, et al. Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label, randomised controlled trial. Lancet Oncol. 2013;14:346–53. One of the only randomized trials published to date comparing topical vs ablative therapies for AIN. Small and single institution but well done.

    Article  PubMed  CAS  Google Scholar 

  34. Goldstone RN, Goldstone AB, Russ J, Goldstone SE. Long-term follow-up of infrared coagulator ablation of anal high-grade dysplasia in men who have sex with men. Dis Colon Rectum. 2011;54(10):1284–92.

    Article  PubMed  Google Scholar 

  35. Weis SE, Vecino I, Pogoda JM, Susa JS. Treatment of high-grade anal intraepithelial neoplasia with infrared coagulation in a primary care population of HIV-infected men and women. Dis Colon Rectum. 2012;55(12):1236–43.

    Article  PubMed  Google Scholar 

  36. Smulian AG, Moore DM, Roberston JC, et al. Phase I study demonstrates safety and tolerability of radiofrequency ablation (RFA) of the anal mucosa. HIV Clinical Trials. 2014;15(1):36–44.

    Article  PubMed  Google Scholar 

  37. • Goldstone RN, Hasan SR, Drury S, et al. A trial of radiofrequency ablation for anal intraepithelial neoplasia. Int J Color Dis. 2017;32:357–65. Interesting emerging technique for AIN ablation, which is in need of further study.

    Article  Google Scholar 

  38. •• AIDS Malignancy Consortium. ANCHOR Study: Anal Cancer/HSIL Outcomes Research Study. ClinicalTrials.gov Identifier: NCT02135419. This ongoing trial will provide by far the best evidence to date regarding management and surveillance of high-grade AIN.

  39. Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, et al. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015;372:711–23.

    Article  PubMed  CAS  Google Scholar 

  40. Giuliano AR, Palefsky JM, Goldstone S, Moreira ED Jr, Penny ME, Aranda C, et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011;364:401–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. • Swedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis. 2012;84(7):891–8. A quality retrospective review displaying efficacy of HPV vaccination in reducing HGAIN recurrence after treatment.

    Article  Google Scholar 

  42. Agnieszka K, Riemer AB. The invisible enemy—how human papillomaviruses avoid recognition and clearance by the host immune system. Open Virol J. 2012;6:249–56.

    Article  Google Scholar 

  43. Deshmukh AA, Chhatwal J, Chiao EY, Nyitray AG, Das P, Cantor SB. Long-term outcomes of adding HPV vaccine to the anal intraepithelial neoplasia treatment regimen in HIV-positive men who have sex with men. Clin Infect Dis. 2015;61:1527–35.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Deshmukh AA, Chiao EY, Cantor SB, Stier EA, Goldstone SE, Nyitray AG, et al. Management of precancerous anal intraepithelial lesions in HIV-positive MSM: clinical and cost effectiveness. Cancer. 2017;123:4709–19.

    Article  PubMed  Google Scholar 

  45. Juhl ME, Seferovic V, Antonijevic S, Krunic A. Combined treatment of anogenital HPV infection with cryodestruction, podophyllin 25% and post-ablation immunomodulation with sinecatechins 15% ointment—retrospective analysis. Int J STD AIDS. 2016;27:1071–8.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Division of Colon and Rectal Surgery, University of South Alabama, 2451 USA Medical Center Drive, Mastin Building, Suite 702, Mobile, AL, 36617, USA

    Paul Rider, John Hunter & Leander Grimm

Authors
  1. Paul Rider
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leander Grimm
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul Rider.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Large Intestine

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rider, P., Hunter, J. & Grimm, L. The Diagnostic and Therapeutic Challenge of Anal Intraepithelial Neoplasia. Curr Gastroenterol Rep 20, 38 (2018). https://doi.org/10.1007/s11894-018-0640-y

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11894-018-0640-y

Keywords

Search

Navigation