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Journal Review Highlight
Thomas F. Purdon, MD, FACOG

Safaeian M, Solomon D, Wacholder S, et al. Risk of Precancer and Follow-up Management Strategies for Women With Human Papillomavirus-Negative Atypical Squamous Cells of Undetermined Significance. Obstet Gynecol. 2007;109(6):1325-1331. Level of Evidence II.

The group from the National Cancer Institute, many of whose members reported on the pivotal ALTS (ASCUS-LSIL Triage Study) in 2001 and 2003, has looked at more follow-up data from those trials. From the study cohorts, they report now on the risk of intraepithelial neoplasia (CIN 3) or worse in women who had an ASCUS  HPV-negative Pap smear after 12 months using cytology or HPV testing or both. In the groups overall, only 22 of 1,539 (1.4%) women who were ASCUS HPV-negative developed CIN 3 or worse during follow-up. The ASCUS HPV-positive group had CIN 3 in 269 of 1,767 (15.2%) women. In the low-risk group (ASCUS HPV-negative), only 7 cases of CIN 3 were diagnosed between 12 and 24 months of follow-up. The authors pointed out that this lower risk limits the power to distinguish meaningful differences in sensitivity among 12-month testing strategies. Specificity of HPV testing (84%) was significantly higher than cytology alone, using ASCUS as the threshold (71%). Using both tests resulted in even lower specificity (61%) at 12 months. Because CIN 3 cases were uncommon, the positive predictive value for subsequent CIN 3 or worse was low (under 3%) for all three modalities. Conversely, the negative predictive value for all three management strategies was very high: 99.7% for HPV testing, 99.82% for cytology, and 100% for both together.

The authors conclude that because of the very low absolute risk of subsequent detection of disease in women with ASCUS HPV-negative, they might be returned to a more routine screening interval, even longer than one year, depending on circumstances such as age and prior screening history. Their data further suggest that if a one-year follow-up is chosen, HPV testing has a higher specificity as well as a lower referral rate compared with cytology using an ASCUS threshold. There were too few cases of CIN 3 to distinguish differences in sensitivity among the various testing strategies. Furthermore, combining both HPV testing and cytology at 12 months results in extremely high sensitivity of detection of CIN 3 or worse, but with unacceptably low specificity, high referral rates, and low positive predictive value. They also point out that both Hybrid Capture 2 and PCR results were compared, and several false-negative HC2 tests were found. This would explain the low, but not zero, incidence of CIN 3 in women who were ASCUS HPV-negative. This information adds to our ability to tailor our management of patients with ASCUS HPV-negative Pap smears according to physician assessment of patient history, risk, and reliability for follow-up.

Editors:
Thomas F. Purdon, MD, FACOG
Clinical Professor of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
University of Arizona Health Sciences Center, Tucson, Arizona
Consultant, United Community Health Centers of Arizona

Kenneth D. Hatch, MD
Professor, Obstetrics and Gynecology
University of Arizona College of Medicine
Tucson, Arizona

Thomas F. Purdon, MD, FACOG
Clinical Professor of Obstetrics and Gynecology
Department of Obstetrics and Gynecology
University of Arizona Health Sciences Center, Tucson, Arizona
Consultant, United Community Health Centers of Arizona

Dr. Thomas F. Purdon is a recent past-president of the American College of Obstetricians and Gynecologists (ACOG), as well as past-president of the advocacy group Ob-Gyns for Women’s Health. He was previously on the governing board for the Jacobs Institute for Women’s Health. His research contributions have been in the areas of hormone therapy, estrogen therapy in surgically induced menopausal women, and dysfunctional uterine bleeding for the Surgical Treatment Outcomes Project. Special interest areas include management of abnormal uterine bleeding, hysteroscopy, and endometrial ablation. Dr. Purdon was an ACOG representative to the 2001 ASCCP Consensus Guidelines Conference held in Bethesda, Maryland.

Given his life-long commitment to improving health outcomes for women, Dr. Purdon speaks frequently to the national medical community on the management of abnormal uterine bleeding, risk assessment strategies for breast cancer, and the continuing controversy over hormone therapy. He also serves as a consultant for United Community Health Centers, a community-based group of primary care clinics in southern Arizona that serves women of all socioeconomic levels.

Dr. Purdon was recently chosen as one of the “ Best Doctors in Tucson,” 2005–2006, by Best Doctors, Inc. and as published in Tucson Lifestyle magazine, and Best Doctors in America 2007–2008. He is frequently asked to speak and conduct surgical teaching sessions on endometrial ablation in the United States as well as in Mexico and Central and South America.