Spontaneous preterm birth risk among HPV-vaccinated and -unvaccinated women: a nationwide retrospective cohort study of over 240 000 singleton births.

OBJECTIVE: To determine whether prior human papillomavirus (HPV) vaccination contributes to preterm birth risk. DESIGN: Population-based retrospective cohort study. SETTING: Denmark. POPULATION: A cohort of 243 136 primiparous females born in the period 1961-2004 who had a singleton delivery at >22 weeks of gestation occurring from October 2006 to December 2018. METHODS: High-quality nationwide registries were linked to provide information on demographics, birth outcomes, HPV vaccination status, smoking, body mass index (BMI), and cervical lesions and treatment history. MAIN OUTCOME MEASURES: We assessed the association between HPV vaccination status and spontaneous preterm birth using logistic regression. To address age at vaccination, we performed a stratified analysis by vaccination before and after 17 years of age. RESULTS: In age-adjusted and fully adjusted models, there was a nonsignificant difference in the odds of spontaneous preterm birth between vaccinated and unvaccinated women (OR 1.05 (95% CI 0.99-1.12) and OR 1.04 (95% CI 0.98-1.10), respectively). There was no difference in the odds of spontaneous preterm birth in relation to time between vaccination and pregnancy. In contrast, compared with unvaccinated women, the odds of preterm birth were lower among women vaccinated before the age of 17 years (fully adjusted OR 0.87, 95% CI 0.75-1.00). This association was not present for women vaccinated at ≥17 years of age. CONCLUSIONS: In this large, population-based cohort, we found reduced odds of spontaneous preterm birth among women vaccinated against HPV at an early age compared with women who were unvaccinated. It seems conceivable that HPV vaccination may not only reduce the incidence of cervical cancer and severe precursors, but also reduce the risk of preterm birth related to HPV infection.

Human papillomavirus genotype concordance between Anyplex II HPV28 and linear array HPV genotyping test in anogenital samples.

Anyplex II HPV-28 (HPV-28) can detect individually 28 HPV genotypes. We assessed the agreement between linear array HPV genotyping (LA-HPV) and HPV-28 for detection of 27 HPV genotypes in 410 stored anogenital samples (75 anal samples, 335 physician-collected cervical samples) collected over 5 years from 410 individuals (13 men, 397 women), including 202 HIV-seropositive individuals. HPV DNA was detected in 393 (95.9%, 95% confidence interval [CI]: 93.4-97.4) and 382 (93.2%, 95% CI: 90.3-95.3) samples with HPV-28 and LA-HPV (p = 0.13), respectively, for a good agreement of 96.3% (κ = 0.65). Of the 10503 HPV typing results, 10195 (780 positive, 9577 negative) were concordant, for an agreement of 97.1% (95% CI: 96.7-97.4) and an excellent of κ = 0.82 (95% CI: 0.80-0.84). The mean type-specific concordance for 27 genotypes was 97.0%, 95% CI: 95.8-98.5 (κ = 0.86 ± 0.07, 95% CI: 0.83-0.88). Excellent agreement was obtained individually for all high-risk genotypes (κ = 0.81-0.97) and for most other genotypes except for types 42, 44, 54, 68, and 69. The mean number of types per sample in discordant samples detected with LA-HPV (3.0, 95% CI: 2.7-3.4) was greater than in concordant samples (1.4, 95% CI: 1.3-1.5; p< 0.001). In conclusion, HPV-28 compared favorably with LA-HPV, but was more frequently positive for HPV42 and HPV68.

Management of Isolated Fever in Labour Compared with Clinical Chorioamnionitis in a Quaternary Centre.

OBJECTIVES: To investigate treatment patterns of women with isolated fever in labour and evaluate if variables in the sepsis in obstetrics score (SOS) or fetal tachycardia are associated with treatment differences. Our secondary objective was to compare women with isolated fever in labour with women with clinical chorioamnionitis to identify any clinicodemographic differences. METHODS: A retrospective cohort study of 473 patients at BC Women's Hospital who presented with isolated fever in labour between January 2011 and April 2016 compared with a dataset of 1135 women with clinical chorioamnionitis from 2011 to 2016 in the same institution. RESULTS: In our cohort of isolated fever in labour, antibiotics were given 74.2 % of the time, and the majority received cefazolin and metronidazole (80.9%, of those who received antibiotics). Higher maternal temperature and heart rate at time of first fever and fetal tachycardia were associated with more antibiotic use. Slightly higher maternal temperature was associated with use of a saline bolus and blood cultures. The proportion of women with a SOS greater than 5 increased 4.5-fold from time of first fever to time of maximum SOS. There were fewer cesarean deliveries in the isolated fever in labour group compared with the clinical chorioamnionitis group (22.4% vs. 54.0%; P < 0.0001). CONCLUSIONS: Slightly higher maternal temperature was associated with increased treatment, including antibiotic use, saline bolus administration, and blood cultures. As evidenced by the higher proportion of women with an SOS over 5, women with isolated fever in labour may have a propensity to deteriorate clinically.

Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes.

Importance: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts. Objectives: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population. Design, Setting, and Participants: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2-affected pregnancies in Canada. This analysis presents exploratory, population-level data from 6 Canadian provinces for the period of March 1, 2020, to October 31, 2021. A total of 6012 pregnant persons with a positive SARS-CoV-2 polymerase chain reaction test result at any time in pregnancy (primarily due to symptomatic presentation) were included and compared with 2 contemporaneous groups including age-matched female individuals with SARS-CoV-2 and unaffected pregnant persons from the pandemic time period. Exposure: SARS-CoV-2 infection during pregnancy. Incident infections in pregnancy were reported to CANCOVID-Preg by participating provinces/territories. Main Outcomes and Measures: Maternal and perinatal outcomes associated with SARS-CoV-2 infection as well as risk factors for severe disease (ie, disease requiring hospitalization, admission to an intensive care unit/critical care unit, and/or oxygen therapy). Results: Among 6012 pregnant individuals with SARS-CoV-2 in Canada (median age, 31 [IQR, 28-35] years), the greatest proportion of cases were diagnosed at 28 to 37 weeks' gestation (35.7%). Non-White individuals were disproportionately represented. Being pregnant was associated with a significantly increased risk of SARS-CoV-2-related hospitalization compared with SARS-CoV-2 cases among all women aged 20 to 49 years in the general population of Canada (7.75% vs 2.93%; relative risk, 2.65 [95% CI, 2.41-2.88]) as well as an increased risk of intensive care unit/critical care unit admission (2.01% vs 0.37%; relative risk, 5.46 [95% CI, 4.50-6.53]). Increasing age, preexisting hypertension, and greater gestational age at diagnosis were significantly associated with worse maternal outcomes. The risk of preterm birth was significantly elevated among SARS-CoV-2-affected pregnancies (11.05% vs 6.76%; relative risk, 1.63 [95% CI, 1.52-1.76]), even in cases of milder disease not requiring hospitalization, compared with unaffected pregnancies during the same time period. Conclusions and Relevance: In this exploratory surveillance study conducted in Canada from March 2020 to October 2021, SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm birth.

The Efficacy of the Quadrivalent Human Papillomavirus Vaccine in Girls and Women Living With Human Immunodeficiency Virus.

BACKGROUND: Human papillomavirus (HPV) vaccination is safe and efficacious in women without human immunodeficiency virus (HIV). Although good immunogenicity has been observed in women living with HIV (WLWH), efficacy data in this population are needed. METHODS: We enrolled 420 females aged ≥9 years (range, 9-65) living with HIV. Participants were to receive 3 doses of qHPV vaccine (0/2/6 months). The main endpoint was vaccine failure (ie, incident persistent qHPV infection, cervical intraepithelial neoplasia of grade 2 or higher [CIN2+], or genital warts). We compared these rates to published rates in vaccinated and unvaccinated women without HIV as well as unvaccinated WLWH. RESULTS: Among 279 eligible women, median follow-up was 2 years. In the intention-to-treat population, the incidence rate (IR) of persistent qHPV (HPV6/11/16/18) was 2.3 per 100 person-years (/100PY) (95% confidence interval [CI], 1.1-4.1), and IR of genital warts was 2.3/100PY (95% CI, 1.2-4.1). In the per-protocol efficacy population, IR of persistent qHPV was 1.0/100PY (95% CI, 0.3-2.6) and of genital warts was 1.0/100PY (95% CI, 0.3-2.5). No cases of CIN2+ occurred. Reported rates of qHPV-related infection and disease within vaccinated women without HIV, unvaccinated women without HIV, and vaccinated WLWH: 0.1 (95% CI, 0.02-0.03), 1.5 (95% CI, 1.1-2.0), and 1.2 (95% CI, 0.2-3.4) /100PY, respectively. The rate of persistent qHPV among vaccinated WLWH was lower than among unvaccinated WLWH (2.3 vs 6.0/100PY). CONCLUSIONS: Vaccinated WLWH may be at higher risk for vaccine failure than vaccinated women without HIV. However, overall rates of vaccine failure were low, and rates of persistent qHPV were lower than in unvaccinated WLWH.

Cervical Cancer Screening in Immunocompromised Women.

In the context of changing recommendations for cervical cancer screening, differing recommendations in each province, and a lack of guidance for cervical screening of immunocompromised women, this article provides specific recommendations for cervical cancer screening of immunocompromised women in Canada.

Retrospective Cohort Study on the Impact of the COVID-19 Pandemic on Pregnancy Outcomes for Women Living With HIV in British Columbia.

BACKGROUND: For pregnant women living with HIV (WLWH), engagement in care is crucial to maternal health and reducing the risk of perinatal transmission. To date, there have been no studies in Canada examining the impact of the COVID-19 pandemic on pregnant WLWH. METHODS: This was a retrospective cohort study assessing the impact of the pandemic on perinatal outcomes for pregnant WLWH using data from the Perinatal HIV Surveillance Program in British Columbia, Canada. We compared maternal characteristics, pregnancy outcomes, and clinical indicators related to engagement with care between a prepandemic (January 2017-March 2020) and pandemic cohort (March 2020-December 2022). We investigated preterm birth rates with explanatory variables using logistic regression analysis. RESULTS: The prepandemic cohort (n = 87) had a significantly (P < 0.05) lower gestational age at the first antenatal encounter (9.0 vs 11.8) and lower rates of preterm births compared with the pandemic cohort (n = 56; 15% vs 37%). Adjusted odds of preterm birth increased with the presence of substance use in pregnancy (aOR = 10.45, 95% confidence interval: 2.19 to 49.94) in WLWH. There were 2 cases of perinatal transmission of HIV in the pandemic cohort, whereas the prepandemic cohort had none. CONCLUSIONS: The pandemic had pronounced effects on pregnant WLWH and their infants in British Columbia including higher rates of preterm birth and higher gestational age at the first antenatal encounter. The nonstatistically significant increase in perinatal transmission rates is of high clinical importance.

Empiric antibiotics for peripartum bacteremia: A chart review from a quaternary Canadian centre.

OBJECTIVE: To evaluate the effectiveness of empiric antibiotic protocols for peripartum bacteremia at a quaternary institution by describing incidence, microbial epidemiology, clinical source of infection, susceptibility patterns, and maternal and neonatal outcomes. METHODS: Retrospective chart review of peripartum patients with positive blood cultures between 2010 and 2018. RESULTS: The incidence of peripartum bacteremia was 0.3%. The most cultured organisms were Escherichia coli (51, 26.7%), Streptococcus spp. (52, 27.2%), and anaerobic spp. (35, 18.3%). Of the E. coli cases, 54.9% (28), 19.6% (10), and 19.6% (10) were resistant to ampicillin, first- and third-generation cephalosporins, respectively. Clinical sources of infection included intra-amniotic infection/endometritis (115, 67.6%), upper and/or lower urinary tract infection (23, 13.5%), and soft tissue infection (8, 4.7%). Appropriate empiric antibiotics were prescribed in 137 (83.0%) cases. There were 7 ICU admissions (4.2%), 18 pregnancy losses (9.9%), 9 neonatal deaths (5.5%), and 6 cases of neonatal bacteremia (3.7%). CONCLUSION: Peripartum bacteremia remains uncommon but associated with maternal morbidity and neonatal morbidity and mortality. Current empiric antimicrobial protocols at our site remain appropriate, but continuous monitoring of antimicrobial resistance patterns is critical given the presence of pathogens resistant to first-line antibiotics.

HSV-2 infection and HPV incidence, persistence, and precancerous lesions in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Several co-factors for HPV oncogenesis have been proposed, including co-infection with HSV-2. We assessed the relationship between HSV-2 infection and HPV-related outcomes in quadrivalent HPV-vaccinated (qHPV) women living with HIV (WLWH). METHODS: In this multi-site study of immunogenicity and efficacy of the qHPV vaccine in WLWH, visits took place at months -3, 0, 2, 6, 12, 18, 24, and annually thereafter. Participants provided clinical data and cervico-vaginal swabs for HPV DNA detection; baseline serum was tested for HSV-2 type-specific antibodies. We used non-parametric statistics to compare HPV-related outcomes by HSV-2 serostatus and use of anti-HSV medication. RESULTS: 151 baseline serum samples underwent HSV-2 testing. At baseline, median age was 39 years, median CD4 count was 500 cells/mm3, and 70% had an HIV viral load of <50 copies/mL. Baseline HSV-2 seroprevalence was 76.2%. HSV-2 seropositivity was associated with increased age (p = 0.006). Controlling for age and median CD4 count, HSV-2 seropositivity was not associated with HPV incidence, persistence, and precancerous lesions. The use of anti-HSV medications was associated with higher odds of HSIL cytology (OR = 3.35, 95% CI = 1.03,11.26) and a greater number of HPV types detected (OR = 1.18, 95% CI = 1.00,1.39). Results were similar in sensitivity analyses using an index value of 3.5. The presence of HSV lesions during the study was not associated with HPV outcomes. CONCLUSIONS: HSV-2 seropositivity was common in this cohort of WLWH in Canada but was not associated with multiple measures of HPV incidence, persistence, and precancerous lesions. However, the use of anti-HSV medications was associated with HSIL cytology and number of HPV types detected.

Increased frequency and quantity of mucosal and plasma cytomegalovirus replication among Ugandan Adults Living with HIV.

BACKGROUND: Co-infection with HIV can result in impaired control of cytomegalovirus (CMV) replication, increasing the likelihood of disease and onward transmission. The objective of this analysis was to measure the impact of HIV on CMV replication in an intensively-sampled cohort in Kampala, Uganda. METHODS: CMV seropositive men and women aged 18-65, with or without HIV co-infection, were followed for one month. Daily oral swabs and weekly anogenital swabs and plasma were collected. Quantitative CMV PCR was performed on all samples. RESULTS: Eighty-five participants were enrolled and provided ≥1 oral swab; 43 (51%) were HIV-seropositive. People living with HIV (PLWH; median CD4 count 439 cells/mm3; none on antiretrovirals) had 2-4 times greater risk of CMV detection at each anatomical site assessed. At the oral site, 773 of 1272 (61%) of samples from PLWH had CMV detected, compared to 214 of 1349 (16%) among people without HIV. Similarly, the mean CMV quantity was higher among PLWH at all anatomical sites, with the largest difference seen for oral swabs (mean difference 1.63 log/mL; 95% CI 1.13-2.13). Among PLWH, absolute quantity of CD4+ T-cells was not associated with risk of CMV detection. HIV plasma RNA quantity was positively correlated with oral CMV shedding frequency, but not detection at other sites. CONCLUSIONS: Mucosal and systemic CMV replication occurs at higher levels in PLWH than people without HIV, particularly oral shedding, which is a major mode of CMV transmission. Increased CMV replication despite relatively preserved CD4+ T-cell counts suggests that additional interventions are required to improve CMV control in PLWH.

Canadian SARS-CoV-2 serological survey using antenatal serum samples: a retrospective seroprevalence study.

BACKGROUND: Insufficient data on the rate and distribution of SARS-CoV-2 infection in Canada has presented a substantial challenge to the public health response to the COVID-19 pandemic. Our objective was to assess SARS-CoV-2 seroprevalence in a representative sample of pregnant people throughout Canada, across multiple time points over 2 years of the pandemic, to describe the seroprevalence and show the ability of this process to provide prevalence estimates. METHODS: This Canadian retrospective serological surveillance study used existing serological prenatal samples across 10 provinces over multiple time periods: Feb. 3-21, 2020; Aug. 24-Sept. 11, 2020; Nov. 16-Dec. 4, 2020; Nov. 15-Dec. 3, 2021; and results from the province of British Columbia during a period in which the SARS-CoV-2 B.1.1.529 (Omicron) variant was predominant, from Nov. 15, 2021, to June 11, 2022. Age and postal code administrative data allowed for comparison with concurrent polymerase chain reactivity (PCR)-positive results collected by Statistics Canada and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) project. RESULTS: Seropositivity in antenatal serum as early as February 2020 indicates SARS-CoV-2 transmission before the World Health Organization's declaration of the pandemic. Seroprevalence in our sample of pregnant people was 1.84 to 8.90 times higher than the recorded concurrent PCR-positive prevalence recorded among females aged 20-49 years in November-December 2020. Overall seropositivity in our sample of pregnant people was low at the end of 2020, increasing to 15% in 1 province by the end of 2021. Seroprevalence among pregnant people in BC during the Omicron period increased from 5.8% to 43% from November 2021 to June 2022. INTERPRETATION: These results indicate widespread vulnerability to SARS-CoV-2 infection before vaccine availability in Canada. During the time periods sampled, public health tracking systems were under-reporting infections, and seroprevalence results during the Omicron period indicate extensive community spread of SARS-CoV-2 infection.

Human Papillomavirus Infection Among Pregnant Women Living With HIV: A Systematic Review and Meta-Analysis.

BACKGROUND: In the general population, human papillomavirus (HPV) prevalence is reportedly increased during pregnancy, and emerging evidence suggests that it may be associated with adverse pregnancy outcomes. Women living with HIV (WLWH) experience higher rates of both HPV infection and certain adverse pregnancy outcomes, yet there are no prior reviews of HPV infection during pregnancy in WLWH. METHODS: We conducted a systematic review and meta-analysis of pooled and type-specific HPV prevalence and associated pregnancy outcomes among pregnant WLWH and, if available, within-study comparators of women without HIV. Subgroup analyses were performed according to polymerase chain reaction primers used and geographic location. RESULTS: Ten studies describing HPV prevalence in 1594 pregnant WLWH were included. The pooled HPV prevalence in pregnant WLWH was 75.5% (95% confidence interval: 50.2 to 90.4) but ranged widely (23%-98%) between individual studies. Among studies that also assessed HPV prevalence in pregnant women without HIV, the pooled prevalence was lower at 48.1% (95% confidence interval: 27.1 to 69.8). Pregnant WLWH had 54% higher odds of being HPV positive compared with pregnant women without HIV. The most common HPV type detected in pregnant WLWH was HPV16. No studies reported pregnancy outcomes by the HPV status. CONCLUSIONS: High prevalence of HPV was documented in pregnant WLWH, exceeding the prevalence among pregnant women without HIV. The limited research on this topic must be addressed with further studies to inform the use of HPV testing as a screening modality for this population as well as the role of HPV in adverse pregnancy outcomes.

Systematic review of the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnant and lactating individuals and their infants.

BACKGROUND: There is significant risk of complications and vulnerability to severe COVID-19 disease in pregnancy, yet hesitancy exists around COVID-19 vaccination during pregnancy and lactation. OBJECTIVE: To summarize the safety, immunogenicity, and effectiveness of COVID-19 vaccines in pregnancy and lactation. SEARCH STRATEGY: A systematic search of MEDLINE, Embase, PubMed, medRxiv, and bioRxiv. SELECTION CRITERIA: Identified original studies published on pregnant and/or lactating individuals who received one or more doses of a COVID-19 vaccine. DATA COLLECTION AND ANALYSIS: A descriptive summary organized by safety, immunogenicity, and effectiveness outcomes of COVID-19 vaccination in pregnancy and lactation. MAIN RESULTS: In total, 23 studies were identified. Humoral response and functional immunity were interrogated and found. Increasing placental transfer ratios in cord blood were associated with increasing time from the first vaccine dose to delivery. Safety data indicated that pregnant and lactating populations experienced vaccine-related reactions at similar rates to the general population. No increased risk of adverse obstetrical or neonatal outcomes were reported. One study demonstrated that pregnant individuals were less likely to experience COVID-19 when vaccinated. CONCLUSION: COVID-19 vaccination in pregnant and lactating individuals is immunogenic, does not cause significant vaccine-related adverse events or obstetrical and neonatal outcomes, and is effective in preventing COVID-19 disease.

Prevalence, incidence, and risk factors associated with cytomegalovirus infection in healthcare and childcare worker: a systematic review and meta-analysis.

BACKGROUND: Cytomegalovirus (CMV) is transmitted by direct contact with body fluids from infected individuals. Transmission of CMV in households, particularly those with young children, contributes significantly to CMV infection in the general population. However, little is known about the contribution of occupational healthcare or childcare exposure to risk of CMV infection. OBJECTIVES: To determine CMV seroprevalence, incidence of primary infection, and associated risk factors in healthcare and childcare workers. METHODS: Six electronic databases were searched systematically for publications on CMV infection in healthcare and childcare workers until March 7, 2022. Two authors independently evaluated the literature for quality and inclusion in our analyses. The pooled results for seroprevalence, incidence, and relative risk (RR) were determined using a random effects model. Heterogeneity among studies was quantified and further investigated in subgroup analysis and meta-regression. Publication bias was assessed using funnel plot. Statistical analyses were preformed using R version 4.05. RESULTS: Forty-eight articles were included in this meta-analysis (quality assessment: 18 good, 14 fair, and 16 poor). Pooled CMV seroprevalence was 59.3% (95% CI: 49.8-68.6) among childcare workers and 49.5% (95% CI: 40.3-58.7) among healthcare workers, and pooled incidences of primary CMV infection per 100 person-years were respectively 7.4 (95% CI: 3.9-11.8) and 3.1 (95% CI: 1.3-5.6). RR for primary infection compared to controls were 3.4 (95% CI: 1.3-8.8) and 1.3 (95% CI: 0.6-2.7) for healthcare and childcare workers, respectively. The odds of CMV seropositivity were 1.6 (95% CI: 1.2-2.3) times higher for childcare workers compared to controls, but not significantly different between healthcare workers and controls (0.9; 95% CI: 0.6-1.2). CMV seropositivity in both groups was significantly associated with having one or more children residing at home, marital status, ethnicity, and age. CONCLUSIONS: Childcare workers, but not healthcare workers, have an increased risk of prevalent and incident CMV infection, a risk that is further increased with the presence of at least one child living at home. These findings suggest that enforcing simple, conventional hygienic measures in childcare settings could help reduce transmission of CMV, and that special precautionary measures for preventing CMV infection may not be required for pregnant healthcare workers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020139756.

Vaccine regulation should require and enforce the inclusion of pregnant and breastfeeding women in prelicensure clinical trials.

Exclusion of pregnant and breastfeeding women from the pivotal randomized controlled trials for COVID-19 vaccines that led to emergency regulatory approval created gaps in data needed for vaccine policy, healthcare provider recommendations, and women's decisions about vaccination. We argue that such knowledge gaps increase potential for vaccine hesitancy and misinformation relating to the health of women and infants, and that these gaps in evidence are avoidable. Over several decades, ethical and scientific guidance, scholarship, and advocacy in favor of pregnant and breastfeeding women's participation in clinical development of vaccines has accumulated. Guidance on how to include pregnant and breastfeeding women in vaccine trials ethically and safely predates the COVID-19 pandemic but has yet to be routinely incorporated in vaccine development. We highlight the important role regulatory authorities could play in requiring that pregnant and breastfeeding women be eligible as volunteer participants in prelicensure vaccine trials for products that are expected to be used in this population. Inclusion of pregnant and breastfeeding populations in clinical trials leading to market approval or emergency use authorization should be undertaken early or concurrently at the time of trials in the general population.

Is 'conflict of interest' a Misnomer? Managing interests in immunization research and evaluation.

Potential conflicts of interest in vaccine research can lead to negative consequences that undermine public trust and thereby put communities at risk. However, collaborations that may give rise to potential conflicts between interests can also greatly facilitate appropriate, scientifically robust, and timely vaccine development, implementation, and evaluation. At present, policies regarding the management of potential conflicts between interests are not ideal. To optimally manage interests in vaccine research, we recommend acknowledging all forms of interests and treating them all as relevant, developing appropriate collaborations, referring to all "conflicts of interest" simply as "interests" or "declarations," and promoting transparency through developing consistent reporting mechanisms.

Vaginal microbiota associated with oncogenic HPV in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Women living with HIV (WLWH) experience higher rates of human papillomavirus (HPV) infection and cervical cancer than women without HIV. Changes in the vaginal microbiome have been implicated in HPV-related disease processes such as persistence of high-risk HPV infection but this has not been well defined in a population living with HIV. METHODS: Four hundred and 20 girls and WLWH, age ≥9, across 14 clinical sites in Canada were enrolled to receive three doses of quadrivalent HPV vaccine for assessment of vaccine immunogenicity. Blood, cervical cytology, and cervico-vaginal swabs were collected. Cervico-vaginal samples were tested for HPV DNA and underwent microbiota sequencing. RESULTS: Principal component analysis (PCA) and hierarchical clustering generated community state types (CSTs). Relationships between taxa and CSTs with HPV infection were examined using mixed-effects logistic regressions, Poisson regressions, or generalized linear mixed-effects models, as appropriate. Three hundred and fifty-six cervico-vaginal microbiota samples from 172 women were sequenced. Human papillomavirus DNA was detected in 211 (59%) samples; 110 (31%) contained oncogenic HPV. Sixty-five samples (18%) were taken concurrently with incident oncogenic HPV infection and 56 (16%) were collected from women with concurrent persistent oncogenic HPV infection. CONCLUSIONS: No significant associations between taxa, CST, or microbial diversity and HPV-related outcomes were found. However, we observed weak associations between a dysbiotic microbiome and specific species, including Gardnerella, Porphyromonas, and Prevotella species, with incident HPV infection.