© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 12, 951,
June 20, 2001
© 2001 Oxford University Press
CORRESPONDENCE |
Re: Comparison of Three Management Strategies for Patients With Atypical Squamous Cells of Undetermined Significance: Baseline Results From a Randomized Trial
Affiliations of authors: H. Strickler, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY; K. Shah, Department of Immunology and Infectious Diseases, The Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD.
Correspondence to: Howard Strickler, M.D., M.P.H., Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Belfer Bldg., Rm. 1308-B, Bronx, NY 10461 (e-mail: Strickle{at}aecom.yu.edu).
The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Epithelial Neoplasia (ASCUS/LSIL) Triage Study (ALTS) is a milestone in efforts to determine the utility of human papillomavirus (HPV) DNA assays as an adjunct to primary cervical cytologic screening. Reporting for the ALTS investigators, Solomon et al. (1) present important data regarding the sensitivity of the Hybrid Capture 2TM (HC 2) HPV DNA test in detecting high-grade cervical intraepithelial neoplasia (CIN) following a borderline cytologic finding. Solomon et al. (1) conclude that, "[HC-2] sensitivity, combined with reasonable specificity for triage, makes HPV testing a viable option for the management of ASCUS [lesions found to be borderline by cytology]."
There is reason for concern, though, that these encouraging findings might be misinterpreted by nonexpert readers. The New York Times (2), for example, reported, "The NCI [National Cancer Institute] said that women who receive borderline abnormal results should be tested for HPV . . . ." If the perception that HPV DNA testing is the "standard of care" were to become widespread in the general public, it could be difficult to change, even if further investigation demonstrates that conservative management is more appropriate. Recent conversations with physicians have indicated that they too often fail to appreciate the preliminary nature of the findings to date.
Secondly, it is important to point out that the utility of HPV triage could possibly vary by age group and specific population characteristics, because of differences in positive predictive value. In sexually active college-aged women, for example, HPV DNA cumulative prevalence is very high (40%–60%), but the prevalence of CIN3 or higher (CIN3+), which increases with age, is very low (3). Few true positives (CIN3+), relative to other groups, and greater potential for false-positive findings (i.e., accurate positive HPV DNA results but no detectable morphologic changes present) could result in a lower positive predictive value (true positives/true positive + false positives) (4). In fact, an increase in the false-positive rate would mean reduced specificity (true negatives/true negatives + false positives). Thus, the performance of the assay itself, in terms of detecting cervical disease, could potentially vary among populations. In keeping with this concern, the investigators reported that the prevalence of HPV varied among clinical centers (patient groups) from 31% to 60%, a nearly twofold difference. It will be important, therefore, for physicians to know the positive likelihood ratio (sensitivity/1 – specificity) for HPV DNA testing in a given age group and population, as well as the pretest probability of disease, before choosing to use HPV triage with a given patient. In populations that vary substantially from the ALTS cohort (e.g., human immunodeficiency virus-positive women), it may be necessary to conduct separate studies. Similar considerations apply to suggestions that HPV triage be used to determine the frequency of cervical cancer screening following a normal cytologic finding (5). Because of its strong study design and exceptional clinical work, the ALTS will carry special weight in the medical community. To begin to address the above issues, it would be helpful for the investigators to present the age- and population-specific data from the current investigation.
REFERENCES
1
Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001;93:293–9.
2 Grady S. Study suggests new option for women with abnormal Pap tests. New York Times Feb 21, 2001; p. 2.
3
Ho GY, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 1998;338:423–8.
4 Sackett DL, Haynes RB, Guyatt GH, Tugwell P. Clinical epidemiology: a basic science for clinical medicine. 2nd ed. Boston (MA): Little, Brown & Co.; 1985.
5 Schneider A, Hoyer H, Lotz B, Leistritza S, Kuhne-Heid R, Nindl I, et al. Screening for high-grade cervical intra-epithelial neoplasia and cancer by testing for high-risk HPV, routine cytology or colposcopy. Int J Cancer 2000;89:529–34.[CrossRef][Web of Science][Medline]cancerlit;20556195
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