Article reviewed
Dalla Pria A, Alfa-Wali M, Fox P, Holmes P, Weir J, Francis N, et al. High-resolution anoscopy screening of HIV positive MSM: longitudinal results from a pilot study. Aids. 2014;28:861-7
Purpose
The prevalence and incidence of anal cancer in the HIV+ population has continued to increase over the last two decades [1, 2]. In fact, the rates of anal cancer in the HIV+ population in North America is now higher than the rates of cervical cancer prior to the introduction of mass screening programs [3].
To date, there have been no randomized control trials or guidelines published for the screening of anal squamous intraepithelial lesions, the precursor to invasive anal cancer. However, several expert groups have recommended screening in at-risk populations [4].
The study described here is a pilot screening program in HIV+ men who have sex with men (MSM) to determine if high resolution anoscopy screening and treatment of high grade squamous intraepithelial lesions (HSIL) influences the development of invasive anal cancer.
Methods
Asymptomatic HIV+ MSM were offered routine anoscopy screening on a voluntary basis through an anoscopy service based in London, UK. Patients received screening through anal cytology and high resolution anoscopy +/- biopsy. Abnormalities on histopathology were classified as anal intraepithelial lesion (AIN) grade 1 (low grade squamous intraepithelial lesion or LSIL), and grades 2 or 3 (HSIL).
Patients who were identified to have LSIL had a follow-up anoscopy at 12 months. Patients with HSIL received treatment (imiquimod, tricholoroacetic acid, or surgical excision), and a follow-up anoscopy at 6 months. Testing for high risk HPV subtypes was also done.
Key findings
A total of 368 asymptomatic HIV+ MSM were screened, with 1497 high resolution anoscopy procedures. The median duration of follow-up was 4.2 years after first anoscopy. 79% of patients had at least 1 high risk HPV subtype. Regarding HIV control, 84% were on antiretroviral therapy, 85% had an undetectable viral load, and the median CD4 count was 441.
In terms of first anoscopy results, 36% had no biopsy (normal anoscopy), 16% had no dysplasia, 15% had AIN-1, 19% had AIN-2, and 13% had AIN-3. There was no difference between the groups for presence of any high risk HPV subtype, duration of HIV infection, proportion on antiretroviral therapy, and proportion with undetectable viral load. Higher grade histology was associated with a lower CD4 count. Overall there was poor correlation of results between anal cytology and anal biopsy (gold standard).
5 of 368 patients progressed to invasive anal cancer during the follow up period, and the median duration of progression was 6.1 years. Of these 5 patients, 3 had initially presented with AIN-3, 1 with AIN-2, and 1 with anal dysplasia on cytology. All patients were treated for HSIL, but developed anal cancer despite treatment. The risk of invasive anal cancer after AIN-3 was 3.2% at 5 years, and after HSIL (AIN-2 + AIN-3) was 0.6% at 5 years.
Implications for practice
There is poor correlation between results of anal cytology and high resolution anoscopy with biopsy, and the latter is the diagnostic test of choice.
Screening high risk population allows for detection of high risk lesions, in particular AIN-3, which has clear association with subsequent development of anal cancer.
Screening provides a window of opportunity to intervene at the premalignant stage (HSIL), and allows invasive anal cancers to be detected at an earlier stage even when treatment for HSIL is not successful.
Further information
Link to PubMed abstract: http://www.ncbi.nlm.nih.gov/pubmed/24441516
References
- Kan M, Wong PH, Press N, Wiseman SM. Colorectal and anal cancer in HIV/AIDS patients: a comprehensive review. Expert Rev Anticancer Ther. 2014;14:395-405.
- Shiels MS, Pfeiffer RM, Gail MH, Hall HI, Li J, Chaturvedi AK, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011;103:753-62.
- Silverberg MJ, Lau B, Justice AC, Engels E, Gill MJ, Goedert JJ, et al. Risk of anal cancer in HIV-infected and HIV-uninfected individuals in North America. Clin Infect Dis. 2012;54:1026-34.
- Chiao EY, Giordano TP, Palefsky JM, Tyring S, El Serag H. Screening HIV-infected individuals for anal cancer precursor lesions: a systematic review. Clin Infect Dis. 2006;43:223-33.