Abstract

We examined the predictors (cytologic interpretations, pathology review, human papillomavirus [HPV] testing results, and colposcopic impressions) of precancer among 545 women with clinical center biopsy diagnoses of cervical intraepithelial neoplasia (CIN) 2 in the ASCUS LSIL Triage Study. Among women with a CIN 2 biopsy result, there was an increasing likelihood that the loop electrosurgical excision procedure (LEEP) tissue sample was diagnosed as precancer (CIN 3) with an increasing number of clinical risk factors of cervical precancer (high-grade squamous intraepithelial lesion [HSIL] cytology, high-grade colposcopy, detection of HPV type 16; Ptrend < .0005). In a multivariate model, using a case definition of worst histologic diagnosis made by the quality control pathology review of biopsy and LEEP tissue samples, HPV-16 was positively associated (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.6–8.8) with a CIN 3 diagnosis, whereas testing negative for HPV or positive for noncarcinogenic HPV types was negatively associated (OR, 0.32; 95% CI, 0.14-0.75) with a CIN 3 diagnosis. Although we found clear evidence that HPV-16 detection helped clarify whether a biopsy specimen diagnosed as CIN 2 represented HPV infection or cervical precancer, this relationship was not sufficiently robust to be clinically useful for reducing the overtreatment of women with HPV infection.

Author notes

Supported by contract Nos. CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, and CN-55105 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services.
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Affiliations of the ALTS Group: National Cancer Institute, Bethesda, MD: D. Solomon, project officer; and M. Schiffman, coproject officer; Clinical centers: University of Alabama at Birmingham: E.E. Partridge, principal investigator; L. Kilgore, coprincipal investigator; and S. Hester, study manager; University of Oklahoma, Oklahoma City: J.L. Walker, principal investigator; G.A. Johnson, coprincipal investigator; and A. Yadack, study manager; Magee-Womens Hospital of the University of Pittsburgh Medical Center Health System, Pittsburgh, PA: R.S. Guido, principal investigator; K. McIntyre-Seltman, coprincipal investigator; R.P. Edwards, investigator; and J. Gruss, study manager; University of Washington, Seattle: N.B. Kiviat, coprincipal investigator; L. Koutsky, coprincipal investigator; and C. Mao, investigator; Colposcopy Quality Control Group: D. Ferris, principal investigator, Medical College of Georgia, Augusta; J.T. Cox, coinvestigator, University of California at Santa Barbara; and L. Burke, coinvestigator, Beth Israel Deaconess Medical Center Hospital, Boston, MA; HPV Quality Control Group: C.M. Wheeler, principal investigator, and C. Peyton-Goodall, Lab Manager, University of New Mexico Health Sciences Center, Albuquerque; and M.M. Manos, coinvestigator, Kaiser Permanente, Oakland, CA; Pathology Quality Control Group: R.J. Kurman, principal investigator, D.L. Rosenthal, coinvestigator, and M.E. Sherman, coinvestigator, Johns Hopkins Hospital, Baltimore, MD; and M.H. Stoler, coinvestigator, University of Virginia Health Science Center, Charlottesville; Quality of Life Group: D.M. Harper, investigator, Dartmouth Hitchcock Medical Center, Lebanon, NH; Westat, Coordinating Unit, Rockville, MD: J. Rosenthal, project director; M. Dunn, data management team leader; J. Quarantillo, senior systems analyst; and D. Robinson, clinical center coordinator; and Digene, Gaithersburg, MD: A. Lorincz, senior scientific officer.