Racial Disparities in Diagnosis and Treatment of Patients With Dermatomyositis of Different Skin Tones.

BACKGROUND: Delays in the diagnosis and treatment of dermatological conditions in minorities are a well-documented health disparity. We aimed to determine if there was a delay in detection and treatment initiation for dermatomyositis (DM) and amyopathic dermatomyositis (ADM) in patients of different skin tones. METHODS: Patients from Montefiore Medical Center who met the criteria for DM and ADM were included in this cohort study. Records were reviewed for date of first documented rash, creatine kinase levels, muscle weakness complaints, and date of first steroid or disease-modifying antirheumatic drug initiation. The median number of days between rash documentation and therapy initiation was compared for patients of different races, including non-Hispanic White, non-Hispanic Black, Hispanic, and other (Asian and unknown). Data were compared in White versus non-White skin. RESULTS: Sixty-three DM and 9 ADM patients met the inclusion criteria. There was a shorter time to treatment initiation in White versus non-White patients, with a median number of 8 days compared with 21 days, respectively ( p = 0.05). Kaplan-Meier curves showed prolonged time to diagnosis and treatment in all other races when compared with White patients ( p = 0.03). DISCUSSION: It took clinicians longer to diagnose and treat DM and ADM in patients of color. The trends observed emphasize the importance of increasing dermatology education of non-White skin to improve detection and treatment of DM and ADM and minimize health disparities.

Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

BACKGROUND: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). METHODS: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[-]/Pap[-] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. RESULTS: Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). "PHS with reflex HPV16/18-genotyping and Pap testing" had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. "Concurrent oncHPV and Pap Testing" (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. CONCLUSIONS: PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

Frequency of high-grade squamous cervical lesions among women over age 65 years living with HIV.

BACKGROUND: Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. OBJECTIVE: This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. STUDY DESIGN: Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women's Interagency HIV Study. Launched in October 1994, the Women's Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. RESULTS: Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0-3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0-8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6-5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5-6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0-9.8] per 100 person-years for women living without HIV; P=.81). CONCLUSION: Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study.

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[-]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[-] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[-] women correlated with lower PRs (ρ = -0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV- + b*PHIV- 2 ; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[-] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[-] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

Enhanced recovery after surgery at cesarean delivery to reduce postoperative length of stay: a randomized controlled trial.

OBJECTIVE: Our objective was to determine whether an enhanced recovery after surgery pathway at the time of cesarean birth would permit a reduction in postoperative length of stay and improve postoperative patient satisfaction compared to standard perioperative care. MATERIALS AND METHODS: Patients undergoing nonemergent cesarean delivery at ≥37 weeks of gestation were randomized to enhanced recovery after surgery or standard care. Enhanced recovery after surgery involved multiple evidence-based interventions bundled into 1 protocol. The primary outcome was discharge on postoperative day 2. Secondary outcome variables included pain medication requirements, breastfeeding rates, and various measures of patient satisfaction. RESULTS: From September 27, 2017, to May 2, 2018, a total of 58 women were randomized to enhanced recovery after surgery and 60 women to standard care. The groups were similar in medical comorbidities and in demographic and perioperative characteristics. Enhanced recovery after surgery was not associated with a significantly increased rate of postoperative day 2 discharges when compared with standard care (8.6% vs 3.3%, respectively; odds ratio, 2.74; 95% confidence interval, 0.51-14.70), but it was associated with a significantly reduced postoperative length of stay when compared with standard care, with a median length of stay of 73.5 hours (interquartile range, 71.08-76.62) vs 75.5 hours (interquartile range, 72.86-76.84) from surgery, difference in median length of stay (-1.92; 95% confidence interval, -3.80 to -0.29). Enhanced recovery after surgery was not associated with a reduction in postoperative narcotic use (117.16 ± 54.17 vs 119.38 ± 47.98 morphine milligram equivalents; mean difference, -2.22; 95% confidence interval, -20.86 to 16.42). More subjects randomized to the enhanced recovery after surgery protocol reported breastfeeding at discharge (67.2% vs 48.3%; P = .046). When patients were surveyed 6 weeks postpartum, those in the enhanced recovery after surgery group were more likely to feel that their expectations were met and that they had achieved their postoperative milestones earlier, and to report continued breastfeeding. CONCLUSION: Enhanced recovery after surgery at cesarean delivery was not associated with an increase in the number of women discharged on postoperative day 2, but that may have been related to factors other than patients' medical readiness for discharge. Evidence that enhanced recovery after surgery at cesarean delivery may have the potential to improve outcomes such as day of discharge is suggested by the observed reduction in overall postoperative length of stay, improved patient satisfaction, and an increase in breastfeeding rates. Even better results may accrue with more provider and patient experience with enhanced recovery after surgery.

Long-term outcome of postmenopausal women with proliferative endometrium on endometrial sampling.

BACKGROUND: Proliferative endometrium has been reported in 15% of endometrial biopsies of women aged 50 years and older. Contrary to endometrial hyperplasia, proliferative endometrium has not been associated with the risk of endometrial cancer. OBJECTIVE: This study aimed to report on the long-term outcome of postmenopausal women who received a diagnosis of proliferative endometrium. STUDY DESIGN: This is a retrospective cohort study of 1808 women aged 55 years and older who underwent endometrial sampling between January 1997 and December 2008. Outcome data were available through February 2018. Women with a proliferative endometrium were compared with those with an atrophic endometrium for future development of endometrial hyperplasia or cancer. A subanalysis was performed for those who presented with postmenopausal bleeding. Uni- and multivariable logistic regression analyses were used to assess for confounders. RESULTS: In this study, 297 women (16.4%) received a diagnosis of proliferative endometrium. Furthermore, 962 women met the inclusion criteria. Among those women, 278 had a proliferative endometrium, and 684 had an atrophic endometrium. Women with a proliferative endometrium were younger (61.2 vs 64.5 years; P<.0001) and had a higher body mass index (33.9 vs 30.6 kg/m2; P<.0001). More African American women had a proliferative endometrium. Both groups had a similar length of surveillance (11.9 vs 11.5 years; P=.27). Women with a proliferative endometrium had a higher risk of developing endometrial hyperplasia or cancer (11.9% vs 2.9%; P<.0001), any endometrial cancer (5.8% vs 1.8%; P=.002), atypical endometrial hyperplasia (2.2% vs 0.4%; P=.02), and nonatypical endometrial hyperplasia (2.0% vs 0.7%; P=.001). The risk of developing endometrial cancer and endometrial hyperplasia remained similar after excluding cases on hormonal replacement therapy (12.2% vs 3%; P=.001). On logistic regression analysis, proliferative endometrium histology (odds ratio, 3.89; 95% confidence interval, 2.03-7.49; P<.0001), age >60 years (odds ratio, 1.98; 95% confidence interval, 1.03-3.82; P=.04), and body mass index >35 kg/m2 (odds ratio, 2.3; 95% confidence interval, 1.09-4.83; P<.0001) remained significant risk factors for progression to cancer. CONCLUSION: One of the 6 postmenopausal women who underwent endometrial sampling had a proliferative endometrium. Furthermore, 11.9% of women developed endometrial hyperplasia or cancer, a 4-fold greater incidence than women with an atrophic endometrium. The findings of this study suggest that long-term monitoring is warranted for women with postmenopausal bleeding and a proliferative endometrium histology. Further studies are needed to examine if a treatment is required to negate the risk of unopposed estrogen.

Adjustment for covariates using summary statistics of genome-wide association studies.

Linear regression is a standard approach to identify genetic variants associated with continuous traits in genome-wide association studies (GWAS). In a standard epidemiology study, linear regression is often performed with adjustment for covariates to estimate the independent effect of a predictor variable or to improve statistical power by reducing residual variability. However, it is problematic to adjust for heritable covariates in genetic association analysis. Here, we propose a new method that utilizes summary statistics of the covariate from additional samples for reducing the residual variability and hence improves statistical power. Our simulation study showed that the proposed methodology can maintain a good control of Type I error and can achieve much higher power than a simple linear regression. The method is illustrated by an application to the GWAS results from the Genetic Investigation of Anthropometric Traits consortium.

Impact of human papillomavirus vaccination on the clinical meaning of cervical screening results.

Women previously vaccinated against human papillomavirus (HPV) type 16 and 18 are now reaching the age (21 years) at which cervical-cancer screening is recommended in the U.S. The impact of HPV vaccination on risks of cervical precancer following a positive and negative screen among women aged 21-24 years who just started routine cervical screening are not well described. Therefore, three-year absolute and relative (RR) cumulative risks of cervical intraepithelial neoplasia grade 2 or more severe diagnoses (≥CIN2) and grade 3 or more severe diagnoses (≥CIN3) were estimated for women undergoing cervical screening at Kaiser Permanente Northern California. Risks were estimated in women aged 21-24 years (n = 75,008) undergoing cervical screening since late 2006, 6 months after HPV vaccination became available; women were categorized vaccinated at ages <18, 18-20, and 21-24 years and compared to those who were unvaccinated. Three-year risks were estimated for normal, low-grade, and high-grade cytology results. Three-year risks of ≥CIN2 and ≥CIN3 for unvaccinated women following low-grade cytology were 10.89% for and 3.70%, respectively. By comparison, Three-year risks of ≥CIN2 and ≥CIN3 were 5.26% (RR = 0.48, 95%CI = 0.24-0.99) and 0.99% (RR = 0.27, 95%CI = 0.06-1.13), respectively, for women vaccinated under the age of 18 years. Three-year ≥CIN2 and ≥CIN3 risks were lower for those HPV vaccinated at younger age for any screening result (ptrend ≤ 0.01 for all comparisons). These data support initiating cervical screening at an older age or changing the management of a low-grade cytology result in women aged 21-24 years who were vaccinated against HPV younger than age of 18 years.

Methotrexate Administration to Patients With Presumed Ectopic Pregnancy Leads to Methotrexate Exposure of Intrauterine Pregnancies.

OBJECTIVE: To report clinical experience with methotrexate (MTX) treatment for suspected but not definite ectopic pregnancy (EP). METHODS: This was a retrospective cohort study. All patients treated with MTX for presumed EP between 2000 and 2016 were included. Demographic, clinical, sonographic, and outcome data were collected and analyzed. RESULTS: A total of 820 patients were treated with MTX, 692 (84.4%) of which were lacking definitive features of EP; 155 (22.4%) failed to follow up until complete resolution and were excluded. Retrospective sonographic categorization was applied to 537 patients; of those patients, 393 (73.2%) were categorized as probable EPs, 136 (25.3%) pregnancies of unknown location (PULs), and 8 (1.5%) probable intrauterine pregnancies (IUPs). Sixteen were eventually diagnosed with IUP: 6 from the probable EPs, 9 from the PULs, and 1 from the probable IUP group. Patients with final diagnosis of IUP had higher values of ß-human chorionic gonadotropin as well as lower prevalence of adnexal mass (38% versus 74%; P = .003), higher prevalence of intracavitary fluid (44% versus 9%; P = .0004) and thicker endometrium (17.1 ± 11.8 versus 9.7 ± 5.6; P = .04). None of the sonographic parameters were able to distinguish patients with IUP. One patient of the 16 with IUP was diagnosed with a viable pregnancy, and 7 additional patients had a possible viable pregnancy. None of them elected to continue the pregnancy. CONCLUSIONS: Most patients with suspected EP who are eligible for medical treatment lack definitive sonographic features of EP. Treatment with MTX in such cases should be delayed, as clinically reasonable, to improve the diagnosis and prevent inadvertent administration of MTX to patients with a viable IUP.

Unplanned hospitalizations in a racially and ethnically diverse population of women receiving chemotherapy for epithelial ovarian cancer.

OBJECTIVES: Unplanned hospital admission following chemotherapy is a measure of quality cancer care. Large retrospective datasets have shown admission rates of 10-35% for women with ovarian cancer receiving chemotherapy. We sought to evaluate the prevalence and associated risk factors for hospital admission following chemotherapy in our racially diverse urban population. METHODS: After IRB approval, clinicopathologic and treatment data were abstracted from all patients with newly diagnosed epithelial ovarian cancer who received chemotherapy at our institution from 2005 to 2016. Two-sided statistical analyses and Cox regression analysis were performed using Stata. RESULTS: Of 217 evaluable patients, 87 (40%) had unplanned admissions following chemotherapy: adjuvant 64 (74%) and neoadjuvant 23(26%). Thirty (14%) had more than one admission. In total, there were 1314 days of hospitalization. The median readmission duration was 3 days. Body mass index and hypertension were predictive of readmission (p < 0.05). When comparing those readmitted more than once to those admitted once, both race and aspirin use were predictive of readmission (p < 0.05). Of those admitted more than once the self-identified race and ethnicity was 12 (40%) Hispanic, 8 (27%) White, 8 (27%) Black and 2 (7%) other. There was a significant difference in disease free (p = 0.01) and overall survival (p = 0.004) for patients with unplanned admission after chemotherapy as compared to those without admission. CONCLUSIONS: Readmission rates in our racially diverse patient population were higher than previously reported in the literature. Identifying patients at risk of readmission may play a role in chemotherapy decision-making, and resource allocation including patient care navigators.

Generalized linear mixed model for binary outcomes when covariates are subject to measurement errors and detection limits.

Longitudinal measurement of biomarkers is important in determining risk factors for binary endpoints such as infection or disease. However, biomarkers are subject to measurement error, and some are also subject to left-censoring due to a lower limit of detection. Statistical methods to address these issues are few. We herein propose a generalized linear mixed model and estimate the model parameters using the Monte Carlo Newton-Raphson (MCNR) method. Inferences regarding the parameters are made by applying Louis's method and the delta method. Simulation studies were conducted to compare the proposed MCNR method with existing methods including the maximum likelihood (ML) method and the ad hoc approach of replacing the left-censored values with half of the detection limit (HDL). The results showed that the performance of the MCNR method is superior to ML and HDL with respect to the empirical standard error, as well as the coverage probability for the 95% confidence interval. The HDL method uses an incorrect imputation method, and the computation is constrained by the number of quadrature points; while the ML method also suffers from the constrain for the number of quadrature points, the MCNR method does not have this limitation and approximates the likelihood function better than the other methods. The improvement of the MCNR method is further illustrated with real-world data from a longitudinal study of local cervicovaginal HIV viral load and its effects on oncogenic HPV detection in HIV-positive women.

Racial Differences in Survival From Epithelial Ovarian Cancer Are Associated With Stage at Diagnosis and Use of Neoadjuvant Therapy: A 10-Year Single-Institution Experience With a Racially Diverse Urban Population.

OBJECTIVE: The aim of this study was to evaluate the racial/ethnic disparities in ovarian cancer survival in a diverse population. METHODS: We performed a retrospective cohort study evaluating all patients with epithelial ovarian cancer who received primary treatment at Montefiore Medical Center from 2005 to 2015. Clinicopathologic and survival data were abstracted from medical records. Two-sided statistical analyses were performed using SAS 9.3. RESULTS: Three hundred forty-four evaluable patients were identified: 85 (25%) black, 107 (31%) white, 74 (21%) Hispanic, and 78 (23%) other. Black patients were more likely to present with stage IV disease (P = 0.01) and receive neoadjuvant chemotherapy (P < 0.01). By Kaplan-Meier survival analysis, black race was associated with worse recurrence-free survival (P = 0.01) when compared with white race. In multivariate Cox regression model including treatment and stage, race was no longer associated with survival. In a separate multivariate analysis, utilization of neoadjuvant chemotherapy was associated with black race (odds ratio 4.03; 95% confidence interval, 1.56-10.38; P < 0.01) and stage IV disease (odds ratio 3.44; 95% confidence interval, 1.66-7.12; P < 0.01). CONCLUSIONS: In a racially/ethnically diverse population with ovarian cancer, black women had poorer disease-free survival than whites, although this was statistically accounted for by stage at diagnosis and use of neoadjuvant therapy. Research is needed to determine how differences in access/utilization of care and genetic differences in tumor biology may impact late stage diagnosis and use of neoadjuvant chemotherapy among black ovarian cancer patients.

Utilization of intraperitoneal chemotherapy for optimally cytoreduced advanced stage epithelial ovarian cancer: A 10-year single institution experience with a racially diverse urban population.

OBJECTIVES: The goal of our study was to define utilization and clinical results of intraperitoneal (IV/IP) compared to intravenous (IV) chemotherapy in a racially and ethnically diverse population with optimally debulked advanced stage epithelial ovarian cancer. METHODS: After IRB approval, all patients diagnosed with epithelial ovarian cancer that underwent primary cytoreductive surgery at our institution from 2005 to 2016 were identified. Death was verified by the National Social Security Death Index. Patients who received at least one IV/IP cycle were analyzed in the IV/IP cohort. Kaplan-Meier and Cox proportional hazards models were performed. RESULTS: 96 patients with advanced stage optimally cytoreduced epithelial ovarian cancer (median follow up 33months) were identified. 51% and 49% of patients received IV/IP and IV chemotherapy, respectively. 27%, 22%, and 39% of patients were of white, black, and other race. Compared with IV chemotherapy only, IV/IP chemotherapy was associated with longer OS (log rank <0.002) and IV/IP chemotherapy versus IV chemotherapy alone was associated with a lower risk of death (HR=0.31, 95% CI 0.16-0.62, P<0.001). The median overall survival for the IV/IP and IV groups was 76months (95% CI 62 - not estimated) and 38months (95% CI 30-55), respectively. There was a trend toward higher risk of death for patients who completed fewer than 6cycles of IV/IP chemotherapy compared to women who completed 6 IV/IP cycles (HR=3.2, 95% CI 0.98-9.27 (P=0.05). No differences in patient or tumor characteristics were identified between these two groups of patients. CONCLUSIONS: In our racially diverse urban patients, 50% of patients received IV/IP chemotherapy and it was associated with improved overall survival compared to IV chemotherapy alone. Further investigation is needed to identify barriers to use of IV/IP chemotherapy.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

BACKGROUND: Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status. METHODS: 16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4+ T-cell count of > 500 cells/mm3, and 20 were HIV infected with progressive immunosuppression. Vaginal pH was serially measured. RESULTS: The relative abundances of Lactobacillus crispatus and other Lactobacillus species were inversely associated with vaginal pH (all P < .001). High (vs low) L. crispatus relative abundance was associated with decreased HPV detection (odds ratio, 0.48; 95% confidence interval, .24-.96; Ptrend = .03) after adjustment for repeated observation and multiple covariates, including pH and study group. However, there were no associations between HPV and the relative abundance of Lactobacillus species as a group, nor with Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii individually. CONCLUSIONS: L. crispatus may have a beneficial effect on the burden of HPV in both HIV-infected and HIV-uninfected women (independent of pH).

Multitype Infections With Human Papillomavirus: Impact of Human Immunodeficiency Virus Coinfection.

BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes women to genital coinfection with human papillomaviruses (HPVs). Concurrent infection with multiple HPV types has been documented, but its frequency, correlates, and impact on development of precancer are poorly defined in HIV-seropositive women. METHODS: Human immunodeficiency virus-seropositive women and -seronegative comparison women were enrolled in a cohort study and followed every 6 months from 1994 to 2006. Cervicovaginal lavage samples were tested for HPV types using polymerase chain reaction amplification with MY09/MY11 consensus primers followed by hybridization with consensus and HPV type-specific probes. Analyses were performed using generalized estimating equations. RESULTS: Multitype HPV infections were found in 594 (23%) of 2543 HIV-seropositive women and 49 (5%) of 895 HIV-seronegative women (P < 0.0001). Compared with HPV uninfected women, those with multiple concurrent HPV infections were more likely to be younger, nonwhite, and current smokers, with lower CD4 counts and HIV RNA levels. The average proportion of women with multitype HPV infections across visits was 21% in HIV-seropositive women and 3% in HIV-seronegative women (P <0.0001). Compared with infection with 1 oncogenic HPV type, multitype concurrent infection with at least 1 other HPV type at baseline did not measurably increase the risk of ever having cervical intraepithelial neoplasia 3+ detected during follow-up (odds ratio, 0.80; 95% confidence interval, 0.32-2.03, P = 0.65). CONCLUSIONS: Concurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, but multitype infection does not increase precancer risk.

Association of cervical precancer with human papillomavirus types other than 16 among HIV co-infected women.

BACKGROUND: HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer. OBJECTIVE: We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers. STUDY DESIGN: HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3(+)). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3(+) was diagnosed. RESULTS: HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3(+) but only 44 (29%) of 154 HIV-seropositive women with CIN3(+) (P = .01). The lower prevalence of HPV16 in CIN3(+) among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08-0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3(+) (OR, 1.02; 95% CI, 0.53-1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3(+) (OR, 3.9; 95% CI, 1.3-11.8). CONCLUSION: The previously demonstrated increase in CIN3(+) incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test.

BACKGROUND: Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. METHODS: A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). RESULTS: At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts <350, 350-499, and ≥500 cells/µL, respectively, whereas it was 10% (95% CI, 0%-21%) in those without HIV. For CIN-3+, the cumulative risk averaged 4% (95% CI, 1%-8%) in HIV-infected oncHPV-positive women, and 10% (95% CI, 0%-23%) among those positive for HPV type 16. In HIV-infected women with LSIL, CIN-3+ risk was 7% (95% CI, 3%-11%). In multivariate analysis, HIV-infected HPV16-positive women had 13-fold (P = .001) greater CIN-3+ risk than oncHPV-negative women (referent), and HIV-infected women with LSIL had 9-fold (P < .0001) greater risk. CONCLUSIONS: HIV-infected women with a normal Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected.

Incidence of cervical precancers among HIV-seropositive women.

OBJECTIVE: The objective of the study was to estimate the impact of human immunodeficiency virus (HIV) infection on the incidence of high-grade cervical intraepithelial neoplasia (CIN). STUDY DESIGN: HIV-seropositive and comparison seronegative women enrolled in a prospective US cohort study were followed up with semiannual Papanicolaou testing, with colposcopy for any abnormality. Histology results were retrieved to identify CIN3+ (CIN3, adenocarcinoma in situ, and cancer) and CIN2+ (CIN2 and CIN3+). Annual detection rates were calculated and risks compared using a Cox analysis. Median follow-up (interquartile range) was 11.0 (5.4-17.2) years for HIV-seronegative and 9.9 (2.5-16.0) for HIV-seropositive women. RESULTS: CIN3+ was diagnosed in 139 HIV-seropositive (5%) and 19 HIV-seronegative women (2%) (P<.0001), with CIN2+ in 316 (12%) and 34 (4%) (P<.0001). The annual CIN3+ detection rate was 0.6 per 100 person-years in HIV-seropositive women and 0.2 per 100 person-years in seronegative women (P<.0001). The CIN3+ detection rate fell after the first 2 years of study, from 0.9 per 100 person-years among HIV-seropositive women to 0.4 per 100 person-years during subsequent follow-up (P<.0001). CIN2+ incidence among these women fell similarly with time, from 2.5 per 100 person-years during the first 2 years after enrollment to 0.9 per 100 person-years subsequently (P<.0001). In Cox analyses controlling for age, the hazard ratio for HIV-seropositive women with CD4 counts less than 200/cmm compared with HIV-seronegative women was 8.1 (95% confidence interval, 4.8-13.8) for CIN3+ and 9.3 (95% confidence interval, 6.3-13.7) for CIN2+ (P<.0001). CONCLUSION: Although HIV-seropositive women have more CIN3+ than HIV-seronegative women, CIN3+ is uncommon and becomes even less frequent after the initiation of regular cervical screening.