Progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions in HIV-infected and uninfected men

Tong, Winnie W.Y.a; Jin, Fengyib; McHugh, Leo C.c; Maher, Taraa; Sinclair, Bretta; Grulich, Andrew E.b; Hillman, Richard J.a,c,*; Carr, Andrewa,*

doi: 10.1097/QAD.0b013e3283633111
Clinical Science

Objective: To quantify incidence of, and risk factors for, progression to and spontaneous regression of high-grade anal squamous intraepithelial lesions (ASILs).

Design: Retrospective review of patients at St Vincent's Hospital Anal Cancer Screening Clinic during a period when high-grade ASILs were not routinely treated (2004–2011).

Methods: All patients who had an anal Papanicolaou smear or high-resolution anoscopy were included, except for patients with previous anal cancer. High-grade anal intraepithelial neoplasia (HGAIN) was defined as a composite of histologically confirmed grade 2 or 3 anal intraepithelial neoplasia (AIN2/3) and/or high-grade squamous intraepithelial lesion on anal cytology. Analyses were repeated restricting to histologically confirmed AIN3.

Results: There were 574 patients: median age 45 years (interquartile range, IQR 36–51), 99.3% male and 73.0% HIV-infected [median HIV duration was 13.8 years (IQR 6.4–19.8), median CD4+ T-lymphocyte count was 500 cells/μl (IQR 357–662), 83.5% had undetectable plasma HIV viral load]. Median follow-up was 1.1 years (IQR 0.26–2.76). Progression rate to HGAIN was 7.4/100 person-years (95% confidence interval, CI 4.73–11.63). No risk factor for progression to HGAIN was identified; progression to AIN3 was more likely with increasing age (Ptrend = 0.004) and in those who were HIV-infected [hazard ratio 2.8 (95% CI 1.18–6.68) versus HIV-uninfected; P = 0.019], particularly in those whose nadir CD4+ T-lymphocyte count was less than 200 cells/μl (Ptrend = 0.003). In 101 patients with HGAIN, 24 (23.8%) patients had spontaneous regression [rate 23.5/100 person-years (95% CI 15.73–35.02)], mostly to AIN1. Regression was less likely in older patients (Ptrend = 0.048). Two patients with HGAIN developed anal cancer.

Conclusion: High-grade ASILs frequently spontaneously regress. Longer-term, prospective studies are required to determine whether these regressions are sustained.

aCentre for Applied Medical Research, St Vincent's Hospital

bThe Kirby Institute for Infection and Immunity in Society, University of New South Wales

cWestern Sydney Sexual Health Centre, The University of Sydney & Westmead Hospital, Sydney, Australia.

*Richard J. Hillman and Andrew Carr contributed equally to this article.

Correspondence to Dr Winnie Tong, Clinical Research Program, St Vincent's Centre for Applied Medical Research, Level 4, Xavier Building, St Vincent's Hospital, 390 Victoria Street, Sydney, NSW 2010, Australia. E-mail: wtong@stvincents.com.au

Received 27 February, 2013

Revised 12 May, 2013

Accepted 13 May, 2013

Data presented in part at the 14th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV, Washington DC, 19–21 July 2012 and the 13th International Union on Sexually Transmitted Infections World Congress, Melbourne, 15–17 October 2012.

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© 2013 Lippincott Williams & Wilkins, Inc.