Abner P. Korn

Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial.

BACKGROUNDnVaccination against the most common oncogenic human papillomavirus (HPV) types, HPV-16 and HPV-18, could prevent development of up to 70% of cervical cancers worldwide. We did a randomised, double-blind, controlled trial to assess the efficacy, safety, and immunogenicity of a bivalent HPV-16/18 L1 virus-like particle vaccine for the prevention of incident and persistent infection with these two virus types, associated cervical cytological abnormalities, and precancerous lesions.nnnMETHODSnWe randomised 1113 women between 15-25 years of age to receive three doses of either the vaccine formulated with AS04 adjuvant or placebo on a 0 month, 1 month, and 6 month schedule in North America and Brazil. Women were assessed for HPV infection by cervical cytology and self-obtained cervicovaginal samples for up to 27 months, and for vaccine safety and immunogenicity.nnnFINDINGSnIn the according-to-protocol analyses, vaccine efficacy was 91.6% (95% CI 64.5-98.0) against incident infection and 100% against persistent infection (47.0-100) with HPV-16/18. In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV-16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV-16/18 infection. The vaccine was generally safe, well tolerated, and highly immunogenic.nnnINTERPRETATIONnThe bivalent HPV vaccine was efficacious in prevention of incident and persistent cervical infections with HPV-16 and HPV-18, and associated cytological abnormalities and lesions. Vaccination against such infections could substantially reduce incidence of cervical cancer.

Plasma cell endometritis in women with symptomatic bacterial vaginosis

Objective To evaluate the endometrial microbiology and histopathology in women with symptomatic bacterial vaginosis but no signs or symptoms of upper genital tract disease or other vaginal or cervical infections. Methods Endometrial biopsies were performed on 41 women complaining of vaginal discharge or pelvic pain at a sexually transmitted disease clinic. These women had neither culture nor serologic evidence of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Twenty-two women with bacterial vaginosis diagnosed by Gram stain examination of vaginal fluid, but with neither signs nor symptoms of upper genital tract infection, were compared with 19 women who had no evidence of bacterial vaginosis on vaginal fluid Gram stain. Endometrial biopsies were evaluated for histopathologic evidence of plasma cell endometritis and were cultured for N gonorrhoeae, C trachomatis, aerobic and anaerobic bacteria, Mycoplasma species, and Ureaplasma urealyticum. Results Ten of 22 women with bacterial vaginosis had plasma cell endometritis, compared with one of 19 controls (odds ratio [OR] 15, 95% confidence interval [CI] 2–686; P < .01). Bacterial vaginosis-associated organisms were cultured from the endometria of nine of 11 women with and eight of 30 women without plasma cell endometritis (OR 12.4, 95% CI 2–132; P = .002). Conclusion Plasma cell endometritis was frequently present in women with bacterial vaginosis and without other vaginal or cervical infections. This suggests the possibility of an association between bacterial vaginosis and nonchlamydial, nongonococcal, upper genital tract infection.

Pregnancy rates and predictors of conception, miscarriage and abortion in US women with HIV.

Objective: To determine frequency and outcomes of pregnancy in US women with HIV before and after introduction of highly active antiretroviral therapy (HAART). Design: Prospective cohort study at six US centers. Methods: HIV seropositive and at-risk seronegative women reported pregnancy outcomes at 6-month intervals during the period 1 October 1994 to 31 March 2002. Outcomes were tabulated and pregnancy rates calculated. Logistic regression defined outcome correlates. Results: Pregnancy rates were 7.4 and 15.2 per 100 person-years in seropositive and seronegative women, respectively (P < 0.0001). Among seropositives, 119 (36%) pregnancies ended in live birth, six (2%) in stillbirth, 126 (36%) in abortion, 83 (24%) in miscarriage, 16 (5%) in ectopic pregnancy, and two (1%) in other outcomes (P = nonsignificant versus seronegatives). Independent baseline correlates of conception in seropositives included younger age [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.16–1.23], prior abortion (OR, 1.79; 95% CI, 1.25–2.63), lower HIV RNA levels (OR, 1.30; 95% CI, 1.10–1.54 for each log decrease), and being unmarried (OR, 1.59; 95% CI, 1.02–2.44). Baseline antiretroviral use at baseline was linked to lower conception risk (OR, 0.34; 95% CI, 0.49–0.98 for mono- or combination therapy; OR, 0.34; 95% CI, 0.03–4.28 for HAART). Abortion was less likely during the HAART era, (OR, 0.68; 95% CI, 0.35–1.33 during the early HAART era; OR, 0.46; 95% CI, 0.23–0.90 during the later HAART era, compared with before HAART). Conclusions: Women with HIV were less likely to conceive than at-risk uninfected women, but pregnancy outcomes were similar. Abortion became less common after the introduction of HAART.

The accuracy of colposcopic grading for detection of high-grade cervical intraepithelial neoplasia

Objective. To relate aspects of online colposcopic image assessment to the diagnosis of grades 2 and 3 cervical intraepithelial neoplasia (CIN 2+). Methods: To simulate colposcopic assessment, we obtained digitized cervical images at enrollment after acetic acid application from 919 women referred for equivocal or minor cytologic abnormalities into the ASCUS-LSIL Triage Study. For each, 2 randomly assigned evaluators from a pool of 20 colposcopists assessed images using a standardized tool online. We calculated the accuracy of these assessments for predicting histologic CIN 2+ over the 2 years of study. For validation, a subset of online results was compared with same-day enrollment colposcopic assessments. Results. Identifying any acetowhite lesion in images yielded high sensitivity: 93% of women with CIN 2+ had at least 1 acetowhite lesion. However, 74% of women without CIN 2+ also had acetowhitening, regardless of human papillomavirus status. The sensitivity for CIN 2+ of an online colpophotographic assessment of high-grade disease was 39%. The sensitivity for CIN 2+ of a high-grade diagnosis by Reid Index scoring was 30%, and individual Reid Index component scores had similar levels of sensitivity and specificity. The performance of online assessment was not meaningfully different from that of same-day enrollment colposcopy, suggesting that these approaches have similar utility. Conclusions. Finding acetowhite lesions identifies women with CIN 2+, but using subtler colposcopic characteristics to grade lesions is insensitive. All acetowhite lesions should be assessed with biopsy to maximize sensitivity of colposcopic diagnosis with good specificity.

Risk factors for plasma cell endometritis among women with cervical Neisseria gonorrhoeae, cervical Chlamydia trachomatis, or bacterial vaginosis:

OBJECTIVEnWe sought to determine potential risk factors for upper genital tract inflammation in women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis.nnnSTUDY DESIGNnIn a case-controlled study we compared 111 women with cervical Neisseria gonorrhoeae, Chlamydia trachomatis, or bacterial vaginosis (the study group) with 24 women who had negative tests for each of these infections (the control group). We evaluated potential risk factors for upper genital tract inflammation by use of bivariate and then logistic regression analysis.nnnRESULTSnWe found plasma cell endometritis in 53 of 111 women in the study group and 3 of 24 controls (odds ratio = 6.4, 95% confidence interval 1.7 to 35.0). On logistic regression, the study group women who were in the proliferative phase had increased likelihood of plasma cell endometritis (odds ratio = 4.5, 95% confidence interval 1.6 to 12.4).nnnCONCLUSIONnThe proliferative phase of the menstrual cycle seems to be the primary risk factor for ascending infection by organisms associated with pelvic inflammatory disease. This may be due to a hormonal effect or to the loss of the cervical barrier during menstruation.

Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis.

Background: Bacterial vaginosis (BV) is a common vaginal infection caused by a lack of endogenous lactobacilli and overgrowth of pathogens that frequently recurs following antibiotic treatment. Methods: A phase 2a study assessed colonization efficiency, safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by a vaginal applicator. Twenty-four women with BV were randomized in a 3:1 ratio of active product to placebo. Participants used LACTIN-V at 2 × 109 colony-forming units (cfu)/dose or placebo for 5 initial consecutive days, followed by a weekly application over 2 weeks. They returned for follow-up on Days 10 and 28. Results: Sixty-one percent of the 18 women randomized to the LACTIN-V group were colonized with L. crispatus CTV-05 at Day 10 or Day 28. Among LACTIN-V users with complete adherence to the study regimen, 78% were colonized at Day 10 or Day 28. Of the 120 adverse events (AEs) that occurred, 108 (90%) and 12 (10%) were of mild and moderate severity, respectively. AEs were evenly distributed between the LACTIN-V and placebo group. Of the total AEs, 93 (78%) were genitourinary in origin. The most common genitourinary AEs included vaginal discharge (46%), abdominal pain (46%), dysuria (21%), pollakiuria (21%), vaginal odor (21%), and genital pruritus (17%). No grade 3 or 4 AEs or serious AEs occurred and no deep epithelial disruption was seen during colposcopic evaluation. The product was well tolerated and accepted. Conclusions: LACTIN-V colonized well, and was safe and acceptable in women treated for BV.

adherence to Colposcopy Among Women With Hiv Infection

UNLABELLEDnIn the general population, nonadherence to the recommendation to have colposcopy in women with abnormal cytologic smears is estimated at 30% to 80%, but studies have failed to identify consistent risk factors for nonadherence. The purpose of this analysis is to assess adherence to colposcopy in a subset of participants in the Womens Interagency HIV Study (WIHS), an ongoing multisite longitudinal study of HIV infection in women in the United States and determine factors associated with nonadherence. Identification of such predictors would be useful in designing strategies to improve adherence in this group.nnnMETHODSnAdherence to colposcopy was examined in a cohort of 462 women with, or at risk for, HIV infection with abnormal cervical cytology on entry into WIHS. Adherence was defined as having colposcopy done within 6 months of an abnormal cytology result.nnnRESULTSnOverall adherence to colposcopy was 65% (302 of 462). A multivariate logistic regression model revealed that the odds of adherence were significantly lower for the women who were HIV-infected (p = .011), current crack/cocaine users (p = .040), ever too ill to get medical care (p = .033), not recruited by WIHS study staff (p = .004), and less concerned about the care of their children (p = .037). Among HIV-seropositive women, low CD4 counts, high viral loads, and presence of AIDS-defining illness were not predictive of nonadherence.nnnDISCUSSIONnAdherence to colposcopy among WIHS participants was at the upper limit of the reported range in the United States. Chemical dependency and domestic violence may negatively impact on colposcopy adherence whereas supportive study personnel, having health insurance, and concerns about raising ones children appear to be motivators for adherence to colposcopy in this study. HIV infection was a risk factor for nonadherence, but markers of advanced disease were not predictive of nonadherence.

Establishing cutoff scores on assessments of surgical skills to determine surgical competence

OBJECTIVEnThe aim of this study was to establish minimum cutoff scores on intraoperative assessments of surgical skills to determine surgical competence for vaginal hysterectomy.nnnSTUDY DESIGNnTwo surgical rating scales, the Global Rating Scale of Operative Performance and the Vaginal Surgical Skills Index, were used to evaluate trainees while performing vaginal hysterectomy. Cutoff scores were determined using the Modified Angoff method.nnnRESULTSnTwo hundred twelve evaluations were analyzed on 76 surgeries performed by 27 trainees. Trainees were considered minimally competent to perform vaginal hysterectomy if total absolute scores (95% confidence interval) on Global Rating Scale = 18 (16.5-20.3) and Vaginal Surgical Skills Index = 32 (27.7-35.5). On average, trainees met new cutoffs after performing 21 and 27 vaginal hysterectomies, respectively. With the new cutoffs applied to the same cohort of fourth-year obstetrics and gynecology trainees, all residents achieved competency in performing vaginal hysterectomy by the end of their gynecology rotations.nnnCONCLUSIONnStandard-setting methods using cutoff scores may be used to establish competence in vaginal surgery.

Gynecologic disease in women infected with human immunodeficiency virus type 1

Gynecologic disease is commonly encountered in women infected with the human immunodeficiency virus (HIV). The clinical course of cervical intraepithelial neoplasia, invasive cervical cancer, pelvic inflammatory disease, syphilis, and vaginal candidiasis may be altered by HIV infection and may be refractory to standard treatment, especially with increasing degrees of immune suppression. Careful screening for gynecologic disease and vigilant surveillance for treatment failure are important in the care of women infected with HIV.

Phase 1 Dose-ranging Safety Trial of lactobacillus crispatus Ctv-05 for the Prevention of Bacterial Vaginosis

Background: Bacterial vaginosis is a very common vaginal infection. The lack of endogenous lactobacilli and overgrowth of pathogens facilitate numerous gynecological complications. Methods: A phase I dose-ranging safety trial tested the safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) administered by vaginal applicator. Twelve healthy volunteers were enrolled in 3 blocks of 4 (5 × 108, 1 × 109, and 2 × 109 cfu/dose). Each block was randomized in a 3:1 ratio of active product to placebo. Participants used study product for 5 consecutive days, returned for follow-up on days 7 and 14, and had phone interviews on days 2 and 35. Results: All 12 participants took 5 doses and completed study follow-up. Overall, 45 adverse events (AEs) occurred, of which 31 (69%) were genitourinary (GU) AEs. GU AEs appeared evenly distributed between the 3 treatment blocks and between LACTIN-V and placebo arms. The most common GU AEs were vaginal discharge in 5 subjects (42%), abdominal pain in 4 subjects (33%), metrorrhagia in 4 subjects (33%), vulvovaginitis in 4 subjects (33%), vaginal candidiasis in 3 subjects (25%), and vaginal odor in 3 subjects (25%). Forty-one (91%) AEs were mild (grade 1) in severity. All 4 moderate AEs (grade 2) were unrelated to product use. No grade 3 or 4 AEs or serious adverse events (SAE) occurred. Laboratory parameters and colposcopy findings were within normal limits or clinically insignificant. The product was well-tolerated and accepted. Conclusion: All 3 dose levels of LACTIN-V appeared to be safe and acceptable in healthy volunteers.