Medical Policy



Subject: High Resolution Anoscopy Screening for Anal Intraepithelial Neoplasia (AIN) and Squamous Cell Cancer of the Anus
Document #: SURG.00116 Current Effective Date:    09/27/2017
Status: Reviewed Last Review Date:    08/03/2017

Description/Scope

This document addresses the use of high-resolution anoscopy for screening average and high risk individuals for anal dysplasia and anal cancer.  This document does not address the use of high-resolution anoscopy to assist in the diagnosis or treatment of a suspicious anal lesion, anal dysplasia found in prior cytology/biopsy, or rectal trauma.  

Position Statement

Investigational and Not Medically Necessary:

High-resolution anoscopy (with or without brushings/biopsies) is considered investigational and not medically necessary as a screening test for anal dysplasia and cancer of the anus.

Rationale

Anoscopy involves examining the perianal area and the distal rectum and is commonly performed in individuals with anorectal pain, itching, discharge, or bleeding.  High-resolution anoscopy (HRA), also known as colposcopy of the anal canal, is considered more complex than standard anoscopy in that it involves the careful examination of the anal canal using an anoscope and a high-resolution (10–40x magnification) colposcope.  During the procedure, an anoscope is inserted approximately 2 inches into the anal canal.  Then, a standard gynecologic colposcope is used to magnify the area in order to identify any suspicious lesions.  With the aid of 3% acetic acid, suspicious areas are identified as "acetowhite."  Lugol's iodine solution may also be applied to identify normal mucosa.  Acetic acid is continually applied during the examination to manipulate folds, hemorrhoids, or prolapsing mucosa.  If suspicious lesions are found, biopsies are taken and sent for microscopic examination.

HRA has been investigated as a method to identify abnormal anal cytology in high-risk populations and has been proposed as an adjunct tool in anal cytology screening.  Based on similarities between anal intraepithelial neoplasia (AIN) and cervical intraepithelial neoplasia (CIN), anal Papanicolaou (Pap) smear cytology has been proposed for both screening high-risk individuals and surveillance after treatment of AIN.  There have not been randomized or cohort studies to demonstrate improved survival or clinical outcome with anal cytology screening.

The National Comprehensive Cancer Network (NCCN) includes HRA as a diagnostic tool in the work-up of individuals who present with anal margin lesions and anal canal cancer.  With regard to the benefits and limitations of HRA, the NCCN states the following:

High-grade anal intraepithelial neoplasia (AIN) can be a precursor to anal cancer, and treatment of high-grade AIN may prevent the developmental of anal cancer.  AIN can be identified by cytology, HPV testing, digital rectal examination (DRE), high-resolution anoscopy, and/or biopsy.  The spontaneous regression rate of high-grade AIN is not known, and estimates suggest that the progression rates of AIN to cancer in men who have sex with men might be quite low.  However, a prospective cohort study of 550 HIV-positive men who have sex with men found the rate of conversion of high-grade AIN to anal cancer to be 18% (7/38) at a median follow-up of 2.3 years despite treatment.  In this study, screening led to the identification of high-grade AIN and/or anal cancer in 8% of the cohort.

Routine screening for AIN in high-risk individuals such as HIV-positive patients or men who have sex with men is controversial, because randomized controlled trials showing that such screening programs are efficacious at reducing anal cancer incidence and mortality are lacking whereas the potential benefits are quite large. Most guidelines do not recommend anal cancer screening even in high-risk individuals at this time or state that there may be some benefit with anal cytology.  Few guidelines recommend screening for anal cancer with DRE in HIV-positive individuals (NCCN, 2017).

The Centers for Disease Control and Prevention (CDC), in its 2015 Sexually Transmitted Diseases Treatment Guidelines, reports data are insufficient to recommend routine anal cancer screening with anal cytology in persons with HIV infection, men having sex with men (MSM) without HIV infection, and the general population.  "More evidence is needed concerning the natural history of anal intraepithelial neoplasia, the best screening methods and target populations, the safety and response to treatments, and other programmatic considerations before screening can be routinely recommended" (CDC, 2015).

The anal cancer clinical practice guideline published by the European Society for Medical Oncology (ESMO), the European Society of Surgical Oncology (ESSO) and the European Society of Radiotherapy and Oncology (ESTRO) indicates the following:

Screening programs using anal cytology and high-resolution anoscopy have been proposed for high-risk populations (MSM and HIV – women with a history of anal intercourse or other HPV-related anogenital malignancies) based on the achievements obtained in cervical cytology screening. However, no randomised control study has yet demonstrated the advantage of screening in these high-risk populations (Glynne-Jones, 2014).

According to the 2012 Standards Committee of the American Society of Colon and Rectal Surgeons Practice Parameters for Anal Squamous Neoplasms, screening procedures for high-grade (HGAIN) and low-grade (LGAIN) anal intraepithelial neoplasia include anal cytology, colposcopy, biopsy and HRA (level 1C recommendation [strong recommendations based on low or very low quality of evidence]).  However, the practice parameter also provided the following information regarding HRA:

The sensitivity of anal Pap smear evaluation compared with HRA-directed biopsies ranges from 69% to 93% and specificity ranges from 32% to 59%.  Unfortunately, anal cytology in high-risk cohorts such as MSM has false-negative cytology in up to 23% of HIV-negative and 45% for HIV-positive patients.  Although some economic modeling studies have suggested that frequent anal cytology may be a cost-effective method to prevent anal cancer, there have not been any randomized or cohort studies to demonstrate improved survival or outcomes (Steele, 2012). 

The updated practice guideline published by the HIV Medicine Association of the Infectious Diseases Society of America (Aberg, 2014) provides the following guidance:

HIV-infected men and women with human papillomavirus (HPV) infection are at increased risk for anal dysplasia and cancer.  MSM, women with a history of receptive anal intercourse or abnormal cervical Pap test results, and all HIV-infected persons with genital warts should have anal Pap tests. 

This is considered a strong recommendation that is based on high quality evidence (which implies the recommendation can be applied to most individuals in most circumstances and additional research is unlikely to change the committee's confidence in the estimated effect) (Aberg, 2014).  

The Ontario Health Technology Advisory Committee failed to recommend anal dysplasia screening of high-risk individuals at this time due to the low and variable specificity for cytological screening (33%-81%), inadequate evidence of effectiveness for current treatment of precancerous lesions, high recurrence rates, and lack of evidence that cytological screening reduces the risk of developing anal cancer (OHTAC, 2007). 

Further review of the published literature did not reveal evidence that demonstrates that the use of HRA as a screening tool to identify suspicious anal lesions followed by directed biopsy results in an improved clinical outcome.  For the reasons outlined above, the clinical utility of HRA as a screening tool for anal dysplasia and rectal cancer is considered unproven and its use is considered investigational and not medically necessary at the present time.

Background/Overview

Anal intraepithelial neoplasia (AIN) also termed squamous intraepithelial lesion (SIL) is classified into AIN Grade 1 or low-grade squamous intraepithelial lesion (LSIL).  High grade anal squamous intraepithelial lesion (HSIL) is equivalent to more advanced dysplasia, AIN Grade 2 or 3.  AIN lesions are classified using criteria for the evaluation of cervical cytology.  AIN has many disease characteristics in common with cervical intraepithelial neoplasia.  HSIL has the potential to progress to invasive anal cancer (Pineda, 2008).  There is substantial evidence to show that HIV-positive MSM and HIV-positive women are at increased risk for AIN 2 or 3 and are at increased risk for anal cancer.  Other risks for developing anal dysplasia and anal cancer include immunosuppressive therapies, concurrent human papilloma virus (HPV) related disease in other sites, multiple sexual partners, prior history of other sexually-transmitted disease, history of cervical cancer, cervical intraepithelial neoplasia, and cigarette smoking.

Squamous-cell cancer (SCC) of the anus is an uncommon malignancy, detected in approximately 4600 individuals per year in the United States.  The incidence of anal cancer has not declined as a result of highly active antiretroviral therapies (HAART).  The HPV is associated with a number of benign and malignant lesions in the anogenital tract and is recognized as the cause of cervical dysplasia and cancer.  HPV DNA can be detected in up to 91% of individuals with anal HSIL and up to 81% of individuals with anal SCC.  HPV serotypes associated with anal dysplasia include HPV 16, 18, 58, and 45 (Pineda, 2008).

HRA has been investigated as a method to identify abnormal anal cytology amongst high-risk populations and is used as an adjunct tool to the anal Pap smear.  It is also proposed as a tool to visualize areas of anal mucosa at risk for dysplasia to direct biopsy.

Definitions

Anal intraepithelial neoplasia (AIN): Abnormal cellular growth in anal tissue which may eventually progress to cancer. Also termed anal squamous intraepithelial lesions (ASIL).

Anoscope: An instrument used to visualize the anus and lowest portion of the rectum.

Cervical intraepithelial neoplasia (CIN): Abnormal growth and potentially premalignant changes of the squamous cells on the surface of the cervix.

DNA (deoxyribonucleic acid): A type of molecule that contains the code for genetic information.

MSM: Men having sex with men.

Squamous cell cancer: Tumors which are derived from the squamous cells that line the anal margin and most of the anal canal.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Investigational and Not Medically Necessary: 

CPT  
46601 Anoscopy; diagnostic, with high-resolution magnification (HRA) (eg, colposcope, operating microscope) and chemical agent enhancement, including collection of specimen(s) by brushing or washing, when performed
46607 Anoscopy; with high-resolution magnification (HRA) (eg, colposcope, operating microscope) and chemical agent enhancement, with biopsy, single or multiple
   
ICD-10 Diagnosis  
B20 Human immunodeficiency virus [HIV] disease [when specified as a screening procedure]
B97.7 Papillomavirus as the cause of diseases classified elsewhere [when specified as a screening procedure]
Z12.10 Encounter for screening for malignant neoplasm of intestinal tract, unspecified [anus]
Z12.12 Encounter for screening for malignant neoplasm of rectum
Z12.89 Encounter for screening for malignant neoplasm of other sites
   
References

Peer Reviewed Publications:

  1. Goldie SJ, Kuntz KM, Weinstein MC, et al. Cost effectiveness of screening for anal squamous intraepithelial lesions and anal cancer in human immunodeficiency virus-negative homosexual and bisexual men. Am J Med. 2000; 108(8):634-641.
  2. Palefsky JM, Rubin M. The epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin North Am. 2009; 36(1):187-200.
  3. Pineda CE, Welton ML. Controversies in the management of anal high-grade squamous intraepithelial lesions, Minerva Chir; 2008; 63(5):389-399.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Aberg JA, Kaplan JE, Libman H, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2013 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2014; 58(1):1-10.
  2. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015; 64(No. RR-3):1-137.
  3. Glynne-Jones R, Nilsson P, Aschele C, et al. Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Radiother Oncol 2014; 111(3):330-339.
  4. Kaplan JE, Benson C, Holmes KH, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58(RR-4):1-207.
  5. NCCN Clinical Practice Guidelines in Oncology™. © 2017 National Comprehensive Cancer Network, Inc. Anal Carcinoma V2.2017. Revised April 20, 2017. For additional information visit the NCCN website: http://www.nccn.org.index.asp. Accessed on June 6, 2017.
  6. Ontario Health Technology Advisory Committee (OHTAC). Anal dysplasia screening. OHTAC Recommendation. Toronto, ON: Ontario Ministry of Long-Term Care, Medical Advisory Secretariat; July 2007. Available at: http://www.hqontario.ca/english/providers/program/ohtac/tech/recommend/rec_ads_20070927.pdf. Accessed on June 6, 2017.
  7. Steele SR, Varma MG, Melton GB, et al. Practice parameters for anal squamous neoplasms. Dis Colon Rectum. 2012; 55(7):735-749.
Websites for Additional Information
  1. American Cancer Society Detailed Guide: Anal Cancer What Is Anal Cancer? Last revised: January 20, 2016. Available at: http://www.cancer.org/cancer/analcancer/detailedguide/anal-cancer-what-is-anal-cancer. Accessed on June 6, 2017.
Index

High-resolution anoscopy

Document History

Status

Date

Action

Reviewed 08/03/2017 Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Rationale, References and History sections.
Reviewed 08/04/2016 MPTAC review. In the title and throughout the document the term "high resolution anoscopy" was changed to "high-resolution anoscopy". Updated Review date, Rationale, Definitions, References, Websites for Additional Information and History sections of the document.
  01/01/2016 Updated Coding section with 01/01/2016 HCPCS changes, removed G6027, G6028 deleted 12/31/2015; also removed ICD-9 codes.
Reviewed 08/06/2015 MPTAC review. Updated Review date, Rationale, References and History sections of the document.
  01/01/2015 Updated Coding section with 01/01/2015 CPT and HCPCS changes; removed 0226T, 0227T deleted 12/31/2014.
Reviewed 08/14/2014 MPTAC review. Updated Review date, Rationale, References and History sections of the document.
Reviewed 08/08/2013 MPTAC review. Updated Review date, References and History sections of the document.
Reviewed 08/09/2012 MPTAC review. Updated Review date, References and History sections of the document.
Reviewed 08/18/2011 MPTAC review. Updated Review date, References and History sections of the document.
Reviewed 08/19/2010 MPTAC review. Updated Review date, Rationale, References and History sections of the document.
New 05/13/2010 MPTAC review. Initial document development.