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Anal Cancer Risk in PLWH Halved Following Precancerous Lesion Treatment


The new trial was the first to investigate outcomes among a patient population living with HIV (PLWH) who were treated for anal precancerous growths, or high-grade squamous intraepithelial lesions.

Findings of an investigation into anal cancer risk among persons living with HIV (PLWH) demonstrate that treating precancerous anal growths, also known as high-grade squamous intraepithelial lesions (HSILs), could reduce by half the risk those lesions progress to anal cancer.

Results from the phase 3 ANCHOR study (Topical or Ablative Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Squamous Intraepithelial Lesions) were published online today in The New England Journal of Medicine.

“Similar to cervical cancer, anal cancer is preceded by HSILs,” the authors wrote. “Treatment for cervical HSILs reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSILs to prevent anal cancer are lacking.”

There were 4446 participants from 25 US sites included in the final analysis, following 1:1 randomization to either HSIL treatment or active monitoring. The treatment group received office-based ablative procedures, ablation or excision under anesthesia, or topical treatment with 5-fluorouracil (5FU) or imiquimod, as determined by the treating clinician, “in accordance with clinician and patient preference, using method-specific algorithms,” the authors wrote. All had biopsy-proven HSIL and had undergone anal HSIL screening following their invitation to participate in the study.

Results show that cases of anal cancer were diagnosed more than twice as much in the active monitoring group compared with the treatment group. There were 21 diagnoses of anal cancer made in the active monitoring group (402 per 100,000 person-years; 95% CI, 262-616) vs 9 in the treatment group (173 per 100,000 person-years; 95% CI, 90-332).

In addition, there was a 57% lower risk of HSILs progressing to anal cancer in the treatment vs active monitoring group (HR, 0.43; 95% CI, 6%-80%; P = .03). HSIL diagnosis in the study was confirmed through high-resolution anoscopy, and blood samples were used to confirm levels of plasma HIV-1 RNA and CD4 cells.

The primary and secondary study outcomes were time to progression to anal cancer and anal HSIL treatment safety, respectively.

The most common initial in-office treatment was electrocautery ablation in 92.9%, followed by infrared coagulation in 5.6%, ablation or excision under anesthesia in 4.6%, topical 5FU in 7.0%, and topical imiquimod in 1.2%. Most patients were treated via 1 therapeutic method (86.0%).

As with cervical cancer, the human papillomavirus virus (HPV) causes anal cancer. Both are typically preceded by precancerous growths and are considered rare cancers. However, the study investigators wrote, anal cancer is on the rise and more patients are presenting with advanced disease. In addition, anal cancer–related mortality has been on the rise since the 1970s.

Risk of anal cancer is highest among PLWH, especially among men who have sex with other men vs women living with HIV and the general population. The incidence rates are 89, 18.6 to 35.6, and 1.6 cases per 100,000 person-years, respectively.

Study results also show that the transgender patient population of this study had the highest percentage of biopsy-confirmed HSILs, followed by men and then women: 67.1%, 55.1%, and 47.2%, respectively. Overall, 96.6% of the entire study patient population had pathology laboratory–confirmed HSILs, and by the 4-year mark, 0.9% of the treatment group and 1.8% of the active-monitoring group received an anal cancer diagnosis.

“Treatment of anal HSIL is particularly challenging in PLWH owing to a large lesion burden and number as reflected by high rates of HSIL recurrence or metachronous disease with currently available methods of treatment,” the authors wrote. “The high rate of anal cancer in the treatment group highlights the need for more effective HSIL treatment approaches and for close follow-up after HSIL treatment.”

To make progress in the space, the authors stress that stronger prevention efforts are needed, not only HIV prevention but secondary programs that encompass HPV exposure and treatment. In addition, due to the high cost of high-resolution anoscopy, “expansion of diagnostic and therapeutic training programs in the use of high-resolution anoscopy is also needed.”


Palefsky JM, Lee JY, Jay N, et al. Treatment of anal high-grade squamous intraepithelial lesions to prevent anal cancer. N Engl J Med. Published online June 15, 2022.

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