Impact of loop electrosurgical excision procedure for cervical intraepithelial neoplasia on HIV-1 genital shedding: a prospective cohort study.

OBJECTIVE: We sought to examine the impact of the loop electrosurgical excision procedure (LEEP) on the rate and magnitude of HIV-1 genital shedding among women undergoing treatment for cervical intraepithelial neoplasia 2/3 (CIN2/3). DESIGN: Prospective cohort study. POPULATION: Women infected with HIV-1 undergoing LEEP for CIN2/3 in Kisumu, Kenya. METHODS: Participants underwent specimen collection for HIV-1 RNA prior to LEEP and at 1, 2, 4, 6, 10, and 14 weeks post-LEEP. HIV-1 viral load was measured in cervical and plasma specimens using commercial real-time polymerase chain reaction (PCR) assays, to a lower limit of detection of 40 copies per specimen. MAIN OUTCOME MEASURES: Presence and magnitude of HIV-1 RNA (copies per specimen or cps) in post-LEEP specimens, compared with baseline. RESULTS: Among women on highly active antiretroviral therapy (HAART), we found a statistically significant increase in cervical HIV-1 RNA concentration at week 2, with a mean increase of 0.43 log10 cps (95% CI 0.03-0.82) from baseline. Similarly, among women not receiving HAART, we found a statistically significant increase in HIV-1 shedding at week 2 (1.26 log10 cps, 95% CI 0.79-1.74). No other statistically significant increase in concentration or detection of cervical HIV-1 RNA at any of the remaining study visits were noted. CONCLUSIONS: In women infected with HIV undergoing LEEP, an increase in genital HIV shedding was observed at 2 but not at 4 weeks post-procedure. The current recommendation for women to abstain from vaginal intercourse for 4 weeks seems adequate to reduce the theoretical increased risk of HIV transmission following LEEP.

Preferences for surveillance strategies for women treated for high-grade precancerous cervical lesions.

OBJECTIVES: Data are lacking on how women view alternative approaches to surveillance for cervical cancer after treatment of high-grade cervical intraepithelial neoplasia. We measured and compared patient preferences (utilities) for scenarios with varying surveillance strategies and outcomes to inform guidelines and cost-effectiveness analyses of post-treatment surveillance options. METHODS: English- or Spanish-speaking women who had received an abnormal Pap test result within the past 2 years were recruited from general gynecology and colposcopy clinics and newspaper and online advertisements in 2007 and 2008. Participation consisted of one face-to-face interview, during which utilities for 11 different surveillance scenarios and their associated outcomes were elicited using the time tradeoff metric. A sociodemographic questionnaire also was administered. RESULTS: 65 women agreed to participate and successfully completed the preference elicitation exercises. Mean utilities ranged from 0.989 (undergoing only a Pap test, receiving normal results) to 0.666 (invasive cervical cancer treated with radical hysterectomy or radiation and chemotherapy). Undergoing both Pap and HPV tests and receiving normal/negative results had a lower mean utility (0.953) then undergoing only a Pap test and receiving normal results (0.989). Having both tests and receiving normal Pap but positive HPV results was assigned an even lower mean utility (0.909). 15.9% of the respondents gave higher utility scores to the Pap plus HPV testing scenario (with normal/negative results) than to the "Pap test alone" scenario (with normal results), while 17.5% gave the Pap test alone scenario a higher utility score. CONCLUSIONS: Preferences for outcomes ending with normal results but involving alternative surveillance processes differ substantially. The observed differences in utilities have important implications for clinical guidelines and cost-effectiveness analyses.

Outcomes associated with cesarean section versus vaginal breech delivery at a university hospital.

OBJECTIVE: To determine whether vaginal breech delivery is associated with increased morbidity in term breech singletons using strict selection criteria. This study encompasses our previous studies (in 1987 and 1995) and extends our experience to 21 years. STUDY DESIGN: Retrospective cohort study from 1980 to 2001 including term, non-anomalous singleton breech deliveries selected by strict criteria. Univariable and multivariable analyses were performed for neonatal and maternal outcomes. RESULTS: Five hundred and eleven women underwent cesarean section and 214 a trial of labor. We found greater overall maternal morbidity in the cesarean section group (odds ratio (OR) 1.89, 95% confidence interval (CI)=1.34-2.65). In the vaginal delivery group, neonates were more likely to have had >1 day of mechanical ventilation (OR 10.0, 95% CI=1.56-63.9). No maternal deaths occurred and no neonatal deaths or seizures occurred. CONCLUSION: Given our findings, offering a trial of vaginal breech delivery to well-counseled strictly selected patients remains an appropriate option.

Clinical breast and pelvic examination requirements for hormonal contraception: Current practice vs evidence.

Clinical breast and pelvic examinations are commonly accepted practices prior to provision of hormonal contraception. Such examinations, however, may reduce access to highly effective contraceptive methods, and may therefore increase women's overall health risks. These unnecessary requirements also involve ethical considerations and unwittingly reinforce the widely held but incorrect perception that hormonal contraceptive methods are dangerous. This article reviews and summarizes the relevant medical literature and policy statements from major organizations active in the field of contraception. Consensus developed during the last decade supports a change in practice: hormonal contraception can safely be provided based on careful review of medical history and blood pressure measurement. For most women, no further evaluation is necessary. Pelvic and breast examinations and screening for cervical neoplasia and sexually transmitted infection, while important in their own right, do not provide information necessary for identifying women who should avoid hormonal contraceptives or who need further evaluation before making a decision about their use.

Cervical neoplasia risk in women provided hormonal contraception without a Pap smear.

The study was conducted to determine whether women using a demonstration program providing hormonal birth control without concurrent pelvic examination (First Stop) are at higher risk of cervical neoplasia compared to women using traditional family planning clinics. Using retrospective ion of medical charts, we compared risk factors for cervical neoplasia among 400 First Stop clients and 400 traditional site clients matched on age, race, and contraceptive method. We determined prevalence of these factors: previous abnormal cervical smear, <16 years at first intercourse, multiple sexual partners, high parity, history of sexually transmitted infections, and current cigarette smoking. First Stop clients were not at greater likelihood of having any risk factor for cervical neoplasia except high parity. First Stop clients who failed to follow through on a referral to a traditional clinic were not more likely to be of higher risk than those who did follow through. Of 13 First Stop clients with the highest risk profiles (previous abnormal cervical smear plus one other risk factor), one did not follow through with referral. First Stop clients choosing hormonal contraception without a pelvic examination do not appear to be at substantially higher risk of cervical neoplasia. Future research should quantify more precisely the risks and benefits of the general application of this strategy on a population level.

Advancing age and cervical cancer screening and prognosis.

OBJECTIVES: To determine associations between advancing age and screening behavior and prognosis in long-term members of a prepaid health plan diagnosed with invasive cervical cancer (ICC). DESIGN: Case series. SETTING: Prepaid health plan. PARTICIPANTS: All women diagnosed with ICC at Kaiser Permanente Medical Care Program-Northern California health plan from 1988 to 1994. MEASUREMENTS: From medical records, we recorded participants' age, stage at diagnosis, tumor histology, and results of and reasons for all previous cervical smears. We limited our analysis to women who had been members of the health plan for at least 30 of the 36 months preceding diagnosis (n = 455). RESULTS: Women in older age groups were less likely than younger women to have been screened within the 3 years before diagnosis (P = .005 for trend). Nonadherence to follow-up of abnormal cervical smears was uncommon (17/455, 3.7%) and not age related (P = .932 for trend). The proportions of ICC that were interval cancers, defined as ICC diagnosed within 3 years of a negative screening smear, were highest in women under age 30 (P = .004 for trend). In multivariate analyses controlling for stage at diagnosis, women age 60 and older were not more likely to die of ICC within 3 years of diagnosis than were women younger than age 60 (odds ratio 1.30, 95% confidence interval 0.75-2.28). CONCLUSION: The disproportionate burden of cervical cancer observed in older women appears to be largely attributable to lack of screening within the 3 years before diagnosis.

The positive predictive value of cervical smears in previously screened postmenopausal women: the Heart and Estrogen/progestin Replacement Study (HERS).

BACKGROUND: The benefits and risks of performing annual cervical smears on postmenopausal women are not well defined. The independent effect of hormone replacement therapy on development of cytologic abnormalities is unknown. OBJECTIVE: To determine the positive predictive value of cervical smears in previously screened postmenopausal women and to determine the effect of oral estrogen plus progestin on incident cervical cytologic abnormalities. DESIGN: Prospective cohort study (incidence) and randomized, double-blind, placebo-controlled trial (hormone therapy). SETTING: 20 U.S. outpatient and community clinical centers. PARTICIPANTS: 2561 women with a uterus and normal cytologic characteristics at baseline. INTERVENTIONS: Annual smears; oral conjugated equine estrogens, 0. 625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, or identical placebo. MEASUREMENTS: Incident cytologic abnormalities (atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, low-grade squamous epithelial lesion, and high-grade squamous epithelial lesion) and final histologic diagnoses. RESULTS: The incidence of new cytologic abnormalities in the 2 years following a normal smear was 110 per 4895 person-years (23 per 1000 person-years [95% CI, 18 to 27 per 1000 person-years]). Among the 103 women with known histologic diagnoses, one had mild to moderate dysplasia. The positive predictive value of any smear abnormality identified 1 year after a normal smear, therefore, was 0% (CI, 0% to 5.0%) (0 of 78 women); the positive predictive value of abnormalities found within 2 years was 0.9% (CI, 0.0% to 3.0%) (1 of 110 women). In hormone-treated compared with non-hormone-treated women, the incidence of cytologic abnormalities was nonsignificantly higher (relative hazard, 1.36 [CI, 0.93 to 1.99]), largely because of a nonsignificant 58% greater incidence of atypical squamous cells of undetermined significance (relative hazard, 1.58 [CI, 0.99 to 2.52]). CONCLUSIONS: Because of a poor positive predictive value, cervical smears should not be performed within 2 years of normal cytologic results in postmenopausal women. Therapy with oral estrogen plus progestin does not significantly affect the incidence of cytologic abnormalities.

Frequency of cervical smear abnormalities within 3 years of normal cytology.

OBJECTIVE: To compare cervical screening outcomes associated with age and three screening intervals, 1, 2, and 3 years. METHODS: We did a prospective cohort study comprising 128,805 women at community-based clinics throughout the United States who were screened for cervical cancer within 3 years of normal smears through the National Breast and Cervical Cancer Early Detection Program. We determined the incidence of cytologic abnormalities defined as atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and suggestive of squamous cell cancer. RESULTS: Over the 3 years after normal smear results, the incidence of new smears interpreted as high-grade SIL or suggestive of squamous cell cancer (high-grade SIL or worse) was 66 of 10,000 for women under 30 years old, 22 of 10, 000 for those 30-49 years, 15 of 10,000 for those 50-64 years, and 10 of 10,000 for those over 65 years. Age-adjusted incidence rates of high-grade SIL or worse were similar for women screened at 9-12 months (25 of 10,000), 13-24 months (29 of 10,000), and 25-36 months (33 of 10,000) after normal smears (P =.46). Age-adjusted incidence rates of ASCUS, the most common cytologic abnormality, did not change (P =.36). Incidence of smears interpreted as low-grade SIL increased as time from the normal smear increased (P =.01). CONCLUSIONS: Within 3 years after normal cytology results, cervical smears interpreted as high-grade SIL or worse are uncommon, and the incidence rate is unrelated to the time since last normal smear. Optimal screening strategies for women with recent normal cytology results should be based on comprehensive modeling studies that incorporate the true risks and benefits of repetitive screening.

Papanicolaou smear history and diagnosis of invasive cervical carcinoma among members of a large prepaid health plan.

BACKGROUND: Despite the widespread use of Papanicolaou (Pap) smear screening, substantial morbidity and mortality from cervical carcinoma continue in the U.S. Although access to screening is a major barrier to use of the Pap smear, invasive cervical carcinoma (ICC) still is observed in health plan members who have comprehensive preventive care coverage. METHODS: For all women diagnosed with ICC between 1988 and 1994 in a large prepaid health plan, the authors retrospectively reviewed the medical records for prediagnosis Pap smear history to identify antecedents to ICC. RESULTS: Of 642 women diagnosed as having ICC, 455 (71%) had been plan members for > or = 30 of the 36 months before diagnosis. Of these 455 women, 240 (53%) had no Pap smear during the 6-36 months prior to diagnosis (i.e., were nonadherent to screening), 127 (28%) had only "normal" Pap smear results, 42 (9%) had at least 1 abnormal Pap smear and were adequately followed, 17 (4%) had at least 1 abnormal result without adequate follow-up, and 29 (6%) were classified as "other." Compared with adherent women, more nonadherent women presented with later stage disease, were symptomatic at the time of diagnosis, were older, and were of a race/ethnicity other than non-Hispanic white. CONCLUSIONS: Nonadherence to screening recommendations was found to be the most important modifiable antecedent to ICC in this population. The rate of incidence of ICC could be reduced by interventions to increase screening in women who do not have Pap smears regularly and by the use of newer screening technologies to reduce the false-negative rate of Pap smears.

New technologies in cervical cytology screening: a word of caution.

Nearly 5000 women in the United States will die of cervical cancer this year and many of those deaths could be prevented. Most incident cases (60%) are associated with absent or deficient screening. Approximately 25% of screening failures are due to errors in cervical sampling or smear interpretation. New techniques for cytology screening such as liquid-based smears and computerized rescreening of slides are being promoted to physicians and the lay public despite limited scientific evaluation. Improving the validity of screening tests is important, but shifting resources for this purpose might cause net harm if the result is fewer screening opportunities for high-risk women. New screening technologies do not address this utilization gap and might widen it by driving the cost of screening out of the reach of high-risk women. Greater decreases in cervical cancer morbidity and mortality would likely result if the same resources were invested in a comprehensive national screening program that targeted women at highest risk.

Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis.

OBJECTIVE: To determine the efficacy of periabortal antibiotics in preventing postabortal upper genital tract infection using data from published trials. DATA SOURCES: We performed a literature search of all studies published from January 1966 to September 1, 1994, using MEDLINE, and we manually searched bibliographies of published articles. MEDLINE search terms included: abortion, infection, prophylaxis, antibiotics, pelvic inflammatory disease (PID), and suction curettage. METHODS OF STUDY SELECTION: Randomized, controlled trials comparing antibiotics with placebo in women undergoing suction curettage abortion before 16 weeks' gestation were identified. TABULATION, INTEGRATION, AND RESULTS: Data were extracted independently by two reviewers, one of whom was blinded to journal, year of publication, authors, and institution. Data from 12 studies were combined using meta-analytic techniques based on a fixed-effects model. The overall summary relative risk (RR) estimate for developing postabortal upper genital tract infection in women receiving antibiotic therapy compared with those receiving placebo was 0.58 (95% confidence interval [CI] 0.47-0.71). Of high-risk women, those with a history of PID had a summary RR estimate of 0.56 (95% CI 0.37-0.84); women with a positive chlamydia culture at abortion had a summary RR estimate of 0.38 (95% CI 0.15-0.92). Of low-risk women, those with no reported history of PID had a summary RR estimate of 0.65 (95% CI 0.47-0.90); in women with a negative chlamydia culture, the summary RR estimate was 0.63 (95% CI 0.42-0.97). The lowest summary RR estimate was among women drawn from populations with a low incidence (5-6%) of postabortal infection (summary RR estimate 0.22, 95% CI 0.11-0.42). The overall 42% decreased risk of infection in women given periabortal antibiotics is similar to the risk reduction demonstrable when only studies published before 1985 are combined (summary RR estimate 0.63, 95% CI 0.44-0.89). CONCLUSION: Our meta-analysis revealed a substantial protective effect of antibiotics in all subgroups of women undergoing therapeutic abortion, even women in low-risk groups. No more placebo-controlled trials should be performed, because women assigned to placebo are exposed to preventable risk. Routine use of periabortal antibiotics in the United States may prevent up to half of all cases of postabortal infections.

Hepatotoxicity with the administration of nifedipine for treatment of preterm labor.

Nifedipine, a calcium channel blocker, is becoming increasingly popular as a tocolytic medication. Previous reports of hepatitis associated with nifedipine in the medical literature have been published. We present the first case reported of a patient with preterm labor treated with nifedipine who had development of a concurrent elevation in serum liver enzyme levels.