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Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer

List of authors.
  • Joel M. Palefsky, M.D., C.M.,
  • Jeannette Y. Lee, Ph.D.,
  • Naomi Jay, R.N., Ph.D.,
  • Stephen E. Goldstone, M.D.,
  • Teresa M. Darragh, M.D.,
  • Hillary A. Dunlevy, M.D.,
  • Isabella Rosa-Cunha, M.D.,
  • Abigail Arons, M.P.H.,
  • Julia C. Pugliese, M.P.H.,
  • Don Vena, N.D.,
  • Joseph A. Sparano, M.D.,
  • Timothy J. Wilkin, M.D.,
  • Gary Bucher, M.D.,
  • Elizabeth A. Stier, M.D.,
  • Maribel Tirado Gomez, M.D.,
  • Lisa Flowers, M.D., M.P.H.,
  • Luis F. Barroso, M.D.,
  • Ronald T. Mitsuyasu, M.D.,
  • Shelly Y. Lensing, M.S.,
  • Jeffrey Logan, P.A.,
  • David M. Aboulafia, M.D.,
  • Jeffrey T. Schouten, M.D.,
  • Juan de la Ossa, M.D.,
  • Rebecca Levine, M.D.,
  • Jessica D. Korman, M.D.,
  • Michael Hagensee, M.D., Ph.D.,
  • Thomas M. Atkinson, Ph.D.,
  • Mark H. Einstein, M.D.,
  • Bernadette M. Cracchiolo, M.D.,
  • Dorothy Wiley, Ph.D., R.N.,
  • Grant B. Ellsworth, M.D.,
  • Cristina Brickman, M.D., M.S.C.E.,
  • and J. Michael Berry-Lawhorn, M.D.
  • for the ANCHOR Investigators Group*

Abstract

Background

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.

Methods

Download a PDF of the Research Summary.

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.

Results

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).

Conclusions

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.)

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Anal Lesion Treatment to Prevent Cancer
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Funding and Disclosures

Supported by the National Cancer Institute (award number 2 UM1 CA121947). In-kind support was provided by Hologic (ThinPrep vials) and Bausch Health (fluorouracil cream).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

The views expressed in this article are those of the authors and do not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

Author Affiliations

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.).

Dr. Palefsky can be contacted at or at the University of California, San Francisco, 513 Parnassus Ave., Rm. S420, Box 0654, San Francisco, CA 94143.

The members of the ANCHOR Investigators Group are listed in the Supplementary Appendix, available at NEJM.org.

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