From the University of California, San Francisco School of Medicine, San Francisco (J.M.P., N.J., T.M.D., A.A., C.B., J.M.B.-L.); University of Arkansas for Medical Sciences, Little Rock (J.Y.L., S.Y.L.); Icahn School of Medicine at Mount Sinai (S.E.G., J.A.S.), Weill Cornell Medicine (T.J.W., G.B.E.), Montefiore Medical Center, Albert Einstein School of Medicine (R.L.), and Memorial Sloan Kettering Cancer Center (T.M.A.) - all in New York; University of Colorado School of Medicine, Aurora (H.A.D.); University of Miami School of Medicine, Miami (I.R.-C.); the Emmes Company, Rockland, MD (J.C.P., D.V.); Anal Dysplasia Clinic Midwest, Chicago (G.B.); Boston University School of Medicine, Boston (E.A.S.); University of Puerto Rico Comprehensive Cancer Center, San Juan (M.T.G.); Emory University School of Medicine, Atlanta (L.F.); Wake Forest University Health Sciences, Winston-Salem, NC (L.F.B.); University of California, Los Angeles Schools of Medicine (R.T.M.) and Nursing (D.W.), Los Angeles; Denver Public Health, Denver (J.L.); University of Washington School of Medicine (D.M.A., J.T.S.) and the Polyclinic, Virginia Mason Medical Center (J.O.) - both in Seattle; Capital Digestive Care, Washington, DC (J.D.K.); Louisiana State University School of Medicine, New Orleans (M.H.); and Rutgers New Jersey Medical School, Newark (M.H.E., B.M.C.).
N Engl J Med. 2022 Jun 16;386(24):2273-2282. doi: 10.1056/NEJMoa2201048.
The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking.
We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer.
Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test).
Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).
与普通人群相比，人免疫缺陷病毒（HIV）感染者的肛门癌发病率要高得多。与宫颈癌类似，肛门癌也是由高级别鳞状上皮内病变（HSIL）发展而来。治疗宫颈 HSIL 可降低宫颈癌的进展风险；然而，缺乏前瞻性研究治疗肛门 HSIL 以预防肛门癌的数据。
我们在美国 25 个地点进行了一项 3 期试验。年龄在 35 岁及以上且经活检证实存在肛门 HSIL 的 HIV 感染者，按照 1:1 的比例随机分配，分别接受 HSIL 治疗或不治疗的主动监测。治疗包括门诊消融术、麻醉下消融或切除，或局部使用氟尿嘧啶或咪喹莫特。主要结局是时间事件分析中的肛门癌进展。治疗组的参与者接受治疗，直到 HSIL 完全消退。所有参与者每 6 个月至少接受一次高分辨率肛门镜检查；治疗组疑似持续 HSIL 每年进行活检，主动监测组每年或任何有癌症担忧时进行活检。
在 4459 名接受随机分组的参与者中，4446 名（99.7%）被纳入癌症进展时间的分析。中位随访 25.8 个月，治疗组诊断出 9 例（173 例/100000 人年；95%置信区间[CI]，90 至 332），主动监测组诊断出 21 例（402 例/100000 人年；95%CI，262 至 616）。治疗组的肛门癌进展率比主动监测组低 57%（95%CI，6 至 80；对数秩检验，P=0.03）。
在经活检证实存在肛门 HSIL 的参与者中，与主动监测相比，治疗肛门 HSIL 可显著降低肛门癌的风险。（由美国国立癌症研究所资助；临床试验.gov 编号，NCT02135419。）
