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Published on: October 12, 2018
Anal carcinoma in human immunodeficiency virus-positive men: results of a prospective study from Germany
A Kreuter1, A Potthoff, N H Brockmeyer
1Department of Dermatology, Ruhr University Bochum, Gudrunstrasse 56, D-44791 Bochum, Germany. a.kreuter@derma.de
Background:
Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). There is a paucity of data published on the progression of high-grade AIN to invasive cancer as well as on clinical and virological characteristics comparing anal margin and anal canal carcinoma.
Objectives:
To search for anal carcinoma and AIN in a large series of HIV-positive MSM, to assess treatment response of anal carcinoma, and to analyse lesional HPV spectrum of anal cancers.
Methods:
Detection of anal carcinoma and AIN was performed using cytology, high-resolution anoscopy, and histology in case of abnormal findings. Additionally, HPV analyses for 36 high- and low-risk α-HPV types were performed in patients with anal carcinoma.
Results:
In total, 446 German HIV-positive MSM were examined within an observation period of 5 years and 10 months. Of these, 116 (26·0%) patients had normal findings, 163 (36·5%) had low-grade AIN, 156 (35·0%) had high-grade AIN, and 11 (2·5%) had anal carcinoma as evidenced by the highest grade of cytology/histology. Five patients with anal cancer, who had refused treatment of their precancerous lesions, had progressed from high-grade AIN to invasive cancer within a median time of 8·6 months. All anal cancers carried high-risk α-HPV types. All five squamous cell carcinomas (SCCs) of the anal canal were HPV16 positive. In contrast, only one of the four anal margin SCCs were HPV16 positive (HPV31, HPV33 and HPV33 + HPV68 were found in the other three anal margin SCCs). HPV59 was found in two adenocarcinomas, one of which additionally carried HPV33. In contrast to the cancer biopsies, a broad spectrum of surface high- and low-risk HPV types was found in anal swabs of the patients. Surgical excision resulted in long-term disease control of all anal margin carcinomas, whereas combined chemoradiotherapy in carcinomas of the anal canal was associated with high recurrence rates, high toxicity, and high mortality.
Conclusions:
Anal carcinoma and AIN are frequent in HIV-positive men, even in patients participating in anal cancer prevention programmes. High-grade dysplasia in these patients can progress to invasive cancer within a short period of time. Anal margin carcinoma and anal canal carcinoma differ substantially in their lesional HPV spectrum, prognosis and treatment response.
Insights
Anal intraepithelial neoplasia (AIN) and anal cancer are common in HIV-positive men who have sex with men (MSM). High-grade AIN can rapidly progress to invasive cancer, necessitating tailored treatment strategies for anal margin versus anal canal cancers.
Area of Science:
- Oncology
- Virology
- Epidemiology
Background:
- Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV)-associated precursor to anal cancer, is prevalent in HIV-positive men who have sex with men (MSM).
- Limited data exist on high-grade AIN progression to invasive cancer and on clinical/virological differences between anal margin and anal canal carcinomas.
Purpose of the Study:
- To identify anal carcinoma and AIN in a large cohort of HIV-positive MSM.
- To evaluate treatment response for anal carcinoma.
- To analyze the HPV spectrum in anal cancers.
Main Methods:
- Cytology, high-resolution anoscopy, and histology were used for AIN and anal cancer detection.
- HPV typing for 36 high- and low-risk α-HPV types was performed on anal cancer biopsies.
- Clinical data on treatment response, recurrence, toxicity, and mortality were collected.
Main Results:
- Of 446 HIV-positive MSM, 26.0% had normal findings, 36.5% low-grade AIN, 35.0% high-grade AIN, and 2.5% anal carcinoma.
- Five patients progressed from high-grade AIN to invasive cancer within a median of 8.6 months.
- Anal cancers were HPV-associated; anal canal SCCs were predominantly HPV16-positive, while anal margin SCCs showed a broader HPV spectrum. Treatment outcomes differed significantly between anal margin and anal canal carcinomas.
Conclusions:
- Anal carcinoma and AIN are frequent in HIV-positive MSM, even within prevention programs.
- High-grade AIN can progress rapidly to invasive cancer in this population.
- Anal margin and anal canal carcinomas exhibit distinct HPV profiles, prognoses, and treatment responses.
