SECOND PRIZE PAPER Risk of Invasive Squamous Carcinoma of the Cervix Associated with Screening Intervals of 1, 2, and 3 Years: A Case–Control Study Walter K. Kinney, MD The Permanente Medical Group, Oakland, CA, and the University of California at San Francisco, CA
M. Miller, PhD, H-Y. Sung, PhD, G. F. Sawaya, MD, K. A. Kearney, PhD, and R. A. Hiatt, MD, PhD Objective: To compare the risks of developing invasive squamous carcinoma of the cervix (ISCC) associated with different lengths of time following a negative Pap test result. Methods: We conducted a matched case– control study using subjects who were members of Kaiser Permanente Medical Care Plan–Northern California Region. Women with an initial diagnosis of ISCC between 1983 and 1995 who had been members of the Health Plan at least 30/36 months before the date of histologic diagnosis comprised the cases (n ⫽ 482). Two controls per case (when available) were matched for age, length of membership, and race (n ⫽ 934). We defined the screening interval as the time between the last negative Pap test result and the histologic diagnosis of invasive malignancy. We defined a negative Pap test result as a result reported as normal or one with a reading not associated with squamous dysplasia or cancer (eg, benign cellular changes, metaplasia). Results: Invasive squamous carcinoma of the cervix was diagnosed in 103, 42, and 28 women at 0 –18-, 19 –30-, and 31– 42-month intervals (respectively) following a negative test result. The odds ratio for 2- versus 1-year intervals was 1.72 (95% CI, 1.12–2.64; P ⫽ 0.013), and for 3- versus 1-year intervals was 2.06 (95% CI, 1.21 –3.50; P ⫽ 0.007). The odds ratio for 3- versus 2-year intervals was 1.20 (95% CI, 0.65–2.21; P ⫽ 0.561). These results were not substantially changed by controlling for the number of previous consecutive negative test results or for ever having had an abnormal test result while a plan member. Conclusions: In this large health plan, the odds ratios for the diagnosis of ISCC following a negative Pap test result were significantly greater for 2- and 3-year intervals than for a 1-year interval. We were unable to demonstrate a significant difference between 3- and 2-year intervals. The relevance of our findings needs to be placed in the context of the low absolute risks of developing ISCC during the first 3 years following a negative Pap test result before making policy recommendations.
VOL. 97, NO 4 (SUPPLEMENT), APRIL 2001
Coenzyme Q10 and ␣-Tocopherol Concentrations in Cervical Intraepithelial Neoplasia and Cervix Cancer Magdy S. Mikhail, MD Bronx-Lebanon Hospital Center, Bronx, NY
Prabhudas R. Palan, PhD, and Seymour L. Romney, MD Objective: To determine any association between plasma coenzyme Q10 (CoQ10) and ␣-tocopherol levels and severity of cervical intraepithelial neoplasia (CIN) and cervical cancer. Methods: Plasma levels of total CoQ10 and ␣-tocopherol were measured by high-performance liquid chromatography in patients with biopsy-confirmed CIN (n ⫽ 55) and cervical cancer (n ⫽ 20) and in normal women with no abnormal Pap test results (n ⫽ 27). Cervicovaginal lavages containing epithelial cells (CVC), obtained from the same subjects, also were analyzed for CoQ10 concentrations. Results: The mean plasma levels of CoQ10 and ␣-tocopherol were significantly (P ⫽ 0.001) lower in patients with CIN and cervical cancer compared with controls. Levels of CoQ10 from CVC were measurable and also were significantly (P ⫽ 0.001) lower in women with CIN. Conclusion: The findings suggest that CoQ10 and ␣-tocopherol antioxidants may play a role in the pathogenesis of CIN. The decrease in CoQ10 and ␣-tocopherol levels may be caused by deficient dietary intake in women with CIN. Alternatively, low antioxidant levels may reflect increased utilization to counteract oxidative stress.
Changes in Platelet Membrane Proteins During Normal Pregnancy Theresa Bacon-Baguley, PhD, RN Grand Valley State University, Allendale, MI
Eriks Lusis, MS, Mike Warzynski, PhD, and Russel Jelsema, MD Purpose: Pregnancy has been described as a hypercoagulable state in which coagulation factors are elevated; however, platelet count may be normal. The purpose of this study was to determine whether distinct functional changes occur between platelets from nonpregnant and pregnant subjects. Methods: Blood collected from nonpregnant and pregnant subjects was incubated with monoclonal antibodies to adhesion (CD29, CD36, CD42a, CD42b); aggregation (CD41, CD61); and activation proteins (CD62, PAC-1); subsequently it was analyzed using flow cytometry.
Monday Papers 3S
Results: There was no statistically significant difference in the expression of GPIIIa (CD61), GPIV (CD36), GPIX (CD42a) and GPIb (CD42b) between the pregnant and nonpregnant group when comparing the mean and peak channel of fluorescence. There was, however, a nearly twofold increase in the binding to integrin B1 (CD29), a platelet integrin used in the attachment of platelets to the extracellular matrix. In addition, there was a 50% increase in both the mean and peak fluorescence in the binding to GPIIb (CD41), a platelet aggregation protein, in the pregnancy group. Platelet activation, identified by the antibody CD62, also was increased in the pregnancy group. Conclusions: These results demonstrate an increase in adhesion, aggregation, and activation proteins in normal pregnancy, which is consistent with the hypercoagulable state of pregnancy.
Accuracy of Computerized Detection of Fetal Heart Rate Patterns Emily F. Hamilton, MD McGill University, Montreal, Quebec, Canada
Michael C. Glaude and Maciej Macieszczak Objective: To measure the agreement of computerized detection of fetal heart rate (FHR) patterns with a panel of clinical experts. Method: Digital signal processing techniques and algorithms were used to measure the FHR features of baseline, variability, accelerations and decelerations. Five obstetricians used proprietary software to review, measure, and label the FHR recordings from 41.8 hours of normal and abnormal examples. A composite opinion was defined based on agreement by a majority (3/5) of the experts. Each individual and the computer were compared with the composite. Results: The following table shows the number of hours spent in baseline or nonbaseline (acceleration or deceleration) according to the composite, the portion of this time correctly labeled by the computer-based method and the range of correct detection by individual doctors.
FHR State Baseline Nonbaseline Total
Percentage by Computer
Lowest percentage by MD
Highest percentage by MD
26.7 15.1 41.8
86.5 91.0 88.2
90.2 89.0 89.3
96.4 96.5 96.5
Conclusions: These physicians were fairly consistent in identifying fetal heart rate features. The performance of the computer was close to the five experts. Further enhancements to the software should bring the performance to the 90% level. It is now possible to study large numbers of tracings and to quantify the association of FHR patterns with newborn status and cord blood gas results.
4S Monday Papers
Do Protease Inhibitors Contribute To Low-Birth-Weight Infants in HIV-Seropositive Gravidas? Phillip J. Goldstein, MD Washington Hospital Center, Washington, DC
Saravanan Manimekalai, PhD, and Shan Sundaram, PhD Objective: HIV-seropositive gravidas, both treated and untreated, have a higher incidence of low-birth-weight infants (LBWIs) than do uninfected women. It is suggested that antiretroviral treatment, including protease inhibitors (PIs), contributes to a higher incidence of LBWI. We here report the effect of a PI on trophoblastic cell production of estradiol (E) and progesterone (P). Methods: In the absence and presence of a PI, nelfinavir, CCL-98 cells were incubated (1 million/10 mL) in ATCC medium #30-2004 with 10% fetal bovine serum for different periods. Estradiol (pg/mL) and progesterone (ng/mL) secreted into the medium were measured by radioimmunoassay kits. The sensitivity and intraassay and interassay precision of the assay were 0.6 pg/mL, 3.5% and 4.1% for E and 0.12 ng/mL, 6.9% and 12% for P, respectively. Results: Estradiol and progesterone secretion into the medium increased linearly for 3 days (E: 0 to 2,974 ⫾ 135; P: 0 to 350 ⫾ 21). Nelfinavir, at median therapeutic dose (5 mg/L) decreased the secretion of E and P by more than 60 ⫾ 7% (E: 297 to 113 and P: 34 to 14) in 1 day. The effect of PI on the synthesis of E and P in the cells and response to different doses of drug are being studied. Conclusion: Nelfinavir decreased the secretion of E and P by trophoblastic cells in culture. The decrease could be caused by an inhibition of the synthesis and secretion of E and P or by an inhibition of the cell growth. The data suggest that the clinically observed increased incidence of LBWI might be caused by a drastic reduction in the amount of E and P secreted or by the inhibition of cell growth or both.
Factors Influencing Pregnancy Outcome in Twin Gestations Alfred Khoury, MD Inova Fairfax Hospital, Falls Church, VA
John R. Barton, MD, Jennifer G. Tarter, MD, Niki K. Bergauer, RN, and Baha M. Sibai, MD Objective: To identify the influence of parity and previous preterm delivery (PPTD) on pregnancy outcome in twin gestations. Methods: A cohort of women with twin gestations completing an outpatient preterm labor surveillance program between
Obstetrics & Gynecology