Experiences with thermal ablation for cervical precancer treatment after self-collection HPV-based screening in the ASPIRE Mayuge randomized trial.

Cervical cancer remains a significant public health burden in low-resourced countries. Thus, the WHO prioritized cervix screening, and recently recommended thermal ablation treatment for cervical precancer. However, there is limited information on side effects during treatment and recovery, and acceptability among those treated. The ASPIRE Mayuge trial recruited women to participate in self-collection cervix screening between 2019 and 2020 (N = 2019). Screen-positive women (N = 531, 26.3%) were referred for visual inspection with acetic acid and thermal ablation treatment, per Uganda Ministry of Health recommendations; 71.2% of those referred attended follow-up. Six months post-screening, a subset of trial participants were recontacted. Those who received thermal ablation completed a survey assessing side effects during and after the procedure, and willingness to recommend the treatment to others. We summarized the results to describe the side effects and acceptability of thermal ablation treatment. Of 2019 participants, 349 (17%) received thermal ablation. A subset of 135 completed the follow-up survey, where 90% reported pain during treatment; however, intensity and duration were low. Over a third of women reported problems with recovery for reasons including pain, discharge and bleeding. Regardless, 98% reported they would recommend the treatment to others. The use of thermal ablation to treat cervical precancer appears to be highly acceptable in this population. While many women reported side effects during the procedure and recovery, the majority said they would recommend the treatment to others. However, given the substantial proportion who reported problems with recovery, efforts should be made to provide additional resources to women after receiving thermal ablation treatment for cervical precancer.

"We Shall Tell them with Love, Inform them what we have Learnt and then Allow them to go" - Men's Perspectives of Self-Collected Cervical Cancer Screening in Rural Uganda: A Qualitative Inquiry.

Uganda has high incidence rates of cervical cancer (47.5/100,000/year) due to limited screening access. In settings where men hold most of the decision-making power, they play an important role in women's uptake of cervical cancer screening. We aimed to capture men's knowledge, beliefs and perspectives about cervical cancer, community-based screening and health system barriers. Focus group discussions were conducted with men in rural Uganda. Data were verbatim translated and transcribed into English. Transcripts were analysed in ATLAS.ti using a deductive approach of thematic content analysis and applied to an implementation research framework. Twenty-three men participated in focus groups. Men held poor knowledge of cervical cancer, its causes and treatment. Men felt screening would be acceptable by women if men and women were educated. Men highlighted health system barriers to accessing screening including: 1) poor-quality health services, 2) large distances to facilities/lack of affordable transportation and 3) lack of health workers/mistreatment by health workers. Men described supporting women through assisting with transportation, psychosocial support and sharing information. They requested services for men to be decentralized alongside community outreaches for cervical cancer screening. Engaging men in the implementation, education and planning of community-based cervical cancer screening programs is critical. Not engaging men is a missed opportunity to provide them with services and education. Concerted efforts must be made in educating men and reducing health system barriers to ensure rural women receive cervical cancer screening and follow-up care in low-income settings. Clinicaltrials.gov, NCT04000503; Registered 27 June 2019.

Declining rates of cervical intraepithelial neoplasia in British Columbia, Canada: An ecological analysis on the effects of the school-based human papillomavirus vaccination program.

Since 2008, girls in British Columbia (BC), Canada, have been offered HPV vaccination through a school-based, publicly funded immunization program. The oldest birth cohort eligible for the vaccination program was born in 1994 and uptake is on average 63%. To evaluate the impact of the HPV vaccine in BC, ecological trends in cervical intraepithelial neoplasia (CIN) rates were assessed in young women before and after the implementation of the HPV vaccination program. Information on all Pap smears and histopathological abnormalities, in calendar years 2004-2017 in women 16-28 years of age in BC were obtained from the population-based BC Cancer Cervix Screening Program database. Rates of CIN 2 and 3 were calculated as the number of cases divided by the number of cytology specimens for that period. Rate ratios (RR) were calculated by negative binomial piecewise regression. Age-centered incidence rates of CIN 2 and 3 in BC declined significantly among women 16-23 years of age after HPV vaccine introduction compared to before vaccine introduction. The overall reduction postvaccination for CIN2 and 3 in women 16-23 years was respectively 62% (95% CI 54-68%) and 65% (95% CI 58-71%). Age-specific rates for CIN2 significantly declined for those 18-22 years of age and for those 19, 20 and 23 years of age for CIN3. Among women 24-28 years of age no decline in CIN2 and 3 rate over time was observed. The observed reduction in CIN 2 and 3 rates since the introduction of the school-based HPV vaccine program might illustrate the population impact of the BC provincial school-based HPV vaccination program.

Cervical Intraepithelial Neoplasia Rates in British Columbia Women: A Population-Level Data Linkage Evaluation of the School-Based HPV Immunization Program.

BACKGROUND: To understand real-world human papillomavirus (HPV) vaccine impact, continuous evaluation using population-based data is critical. We evaluated the early impact of the school-based HPV immunization program on cervical dysplasia in women in British Columbia, Canada. METHODS: Data linkage was performed using records from provincial cervical screening and immunization registries. Precancerous outcomes were compared between unvaccinated and HPV-vaccinated women born 1994-2005. Incidence rate, relative rate (RR), and vaccine effectiveness (VE), using unadjusted and adjusted Poisson regression of cytology (HSIL) and histopathology (CIN2, CIN3, and CIN2+) outcomes, were compared across vaccination status groups. RESULTS: Women who received a complete series of vaccine on schedule between age 9 and 14 years had an adjusted RR = 0.42 (95% confidence interval [CI], 0.31-0.57) for CIN2+ over 7 years of follow-up compared to unvaccinated women, resulting in a VE of 57.9% (95% CI, 43.2%-69.0%). Adjusted RR for HSIL was 0.53 (95% CI, .43-.64), resulting in a VE of 47.1% (95% CI, 35.6%-56.7%). CONCLUSION: Women vaccinated against HPV have a lower incidence of cervical dysplasia compared to unvaccinated women. Immunization between 9 and 14 years of age should be encouraged. Continued program evaluation is important for measuring long-term population impact.

Integrated cervical cancer screening in Mayuge District Uganda (ASPIRE Mayuge): a pragmatic sequential cluster randomized trial protocol.

BACKGROUND: Cervical cancer is almost entirely preventable through vaccination and screening, yet remains one of the 'gravest threats to women's lives' according to the World Health Organization. Specific high-risk subtypes of human papillomavirus (HR-HPV) are well-established as the primary cause of cervical cancer. Uganda has one of the highest cervical cancer incidence rates in the world (54.8 per 100,000) as a result of limited screening access and infrastructure. The integration of a self-collected cervical cancer screening program using HPV testing within existing community-based primary health care services could increase access to screening and reduce cervical cancer rates among Ugandan women. METHODS: Using a pragmatic, sequential, cluster randomized trial design; we will compare the effectiveness of two cervical cancer screening models for self-collected HPV testing: 1) community health worker recruitment (door-to-door); and 2) community health meetings. In Mayuge district, Uganda, 31 villages are randomized to one of two treatment arms. Due to the nature of this trial, blinding is not possible. Women are eligible to participate if they have no previous history of hysterectomy or treatment for cervical cancer or pre-cancer and are aged 25-49 years old. All participants receive an integrated package of cervical cancer screening and education. Samples are tested for HPV using GeneXpert point of care testing. All women who test positive for HR-HPV types are referred to a designated health centre for follow-up inspection by Visual Inspection with Acetic acid (VIA) and treatment with thermal ablation. The primary outcome for the trial is the number of women who attend follow-up for VIA screening at a designated Health Centre after a positive HR-HPV test out of all women screened per arm. Secondary outcomes include: cervical cancer screening knowledge; patient-reported experience measures for self-collected cervical cancer screening; and HPV incidence. DISCUSSION: Results from this study will inform the national scale-up of cervical cancer screening in Uganda, aligning with the World Health Organization's target of achieving cervical cancer elimination through the pillar of increased HPV screening coverage. TRIAL REGISTRATION: ISRCTN, ISRCTN12767014. Registered 14 May 2019, https://doi.org/10.1186/ISRCTN12767014; clinicaltrials.gov, NCT04000503; Registered 27 June 2019, https://clinicaltrials.gov/ct2/show/NCT04000503 PROTOCOL VERSION: January 8, 2020, version 1.

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.

Identifying Barriers to Treatment for Women With Cervical Dysplasia in Rural Northern British Columbia.

OBJECTIVE: This study seeks to identify barriers to colposcopy examination faced by patients living in Northern BC to improve outcomes for women at risk of developing cervical cancer. METHODS: A retrospective chart review (n = 309) was conducted in the four colposcopy clinics in Northern BC to collect information regarding patients who were referred for colposcopy after abnormal cytology. Demographic factors associated with non-attendance were identified as barriers to accessing care. Aggregate data from the Cervical Cancer Screening Program (n = 4265) were used to calculate wait times by health region across BC. RESULTS: The odds of having missed an appointment was highest for women who were pregnant (OR 4.0) or attending site D vs. site A (OR 6.0); however, only clinic location remained significant in a multivariable model. Wait times were longer for women who had ever missed appointments, and varied among the sites, with site A and D having significantly longer wait times than the remaining sites. The Northern Health Authority had the longest overall median colposcopy wait time for high-grade cytology in the province at 41 days longer than the provincial average of 62 days. CONCLUSION: The Northern Health Authority faces unique challenges associated with geography and patient population that are associated with longer wait times for colposcopy when compared with other health authorities in the province.

Community-integrated self-collected HPV-based cervix screening in a low-resource rural setting: a pragmatic, cluster-randomized trial.

Effective approaches to improve coverage of self-collected human papillomavirus (HPV)-based cervix screening (SCS) as well as attendance at treatment for HPV-positive participants are needed to inform policy on optimal integration of cervical cancer screening programs within existing infrastructure in low-resource settings. ASPIRE Mayuge was a pragmatic cluster-randomized trial in rural Mayuge district, Uganda, comparing the superiority of two recruitment implementation strategies for SCS: Door-to-Door versus Community Health Day. Villages were randomized (unblinded) to a strategy, and participants aged 25-49 years with no previous history of hysterectomy or treatment for cervical cancer or pre-cancer were eligible. Participants completed a survey and participated in SCS. The primary outcome was rate of attendance at treatment after a positive SCS. The trial randomized 31 villages and 2,019 participants included in these analyses (Door-to-Door: 16 clusters, 1,055 participants; Community Health Day: 15 clusters, 964 participants). Among HPV-positive participants, attendance at treatment rates were 75% (Door-to-Door) and 67% (Community Health Day) (P = 0.049). Participants in the Community Health Day intervention were less likely to attend treatment compared to Door-to-Door (risk ratio = 0.78, 95% confidence interval: 0.64-0.96). No adverse events were reported. Policymakers in low-resource settings can use these results to guide implementation of SCS programs. ISRCTN registration: 12767014 . ClinicalTrials.gov registration: NCT04000503 .

Maternal vaginal microbiome composition does not affect development of the infant gut microbiome in early life.

Birth mode has been implicated as a major factor influencing neonatal gut microbiome development, and it has been assumed that lack of exposure to the maternal vaginal microbiome is responsible for gut dysbiosis among caesarean-delivered infants. Consequently, practices to correct dysbiotic gut microbiomes, such as vaginal seeding, have arisen while the effect of the maternal vaginal microbiome on that of the infant gut remains unknown. We conducted a longitudinal, prospective cohort study of 621 Canadian pregnant women and their newborn infants and collected pre-delivery maternal vaginal swabs and infant stool samples at 10-days and 3-months of life. Using cpn60-based amplicon sequencing, we defined vaginal and stool microbiome profiles and evaluated the effect of maternal vaginal microbiome composition and various clinical variables on the development of the infant stool microbiome. Infant stool microbiomes showed significant differences in composition by delivery mode at 10-days postpartum; however, this effect could not be explained by maternal vaginal microbiome composition and was vastly reduced by 3 months. Vaginal microbiome clusters were distributed across infant stool clusters in proportion to their frequency in the overall maternal population, indicating independence of the two communities. Intrapartum antibiotic administration was identified as a confounder of infant stool microbiome differences and was associated with lower abundances of Escherichia coli, Bacteroides vulgatus, Bifidobacterium longum and Parabacteroides distasonis. Our findings demonstrate that maternal vaginal microbiome composition at delivery does not affect infant stool microbiome composition and development, suggesting that practices to amend infant stool microbiome composition focus factors other than maternal vaginal microbes.

Disconnected perspectives: Patient and care provider's experiences of substance use in pregnancy.

OBJECTIVE: Generations of colonialism, abuse, racism, and systemic trauma have contributed to Indigenous women in Canada bearing the greatest burden of substance use in pregnancy. Stigma associated with substance use in pregnancy translates into multiple barriers to women engaging in care. Care providers have key interactions that can act as a bridge or a barrier to care. METHODS: Patient journey maps were created for women living with substance use (n = 3) and semi-structured interviews (n = 20) were performed to understand perceptions of maternity-care providers around women with substance use in pregnancy at a regional hospital in northern British Columbia. RESULTS: Patient journey maps showed overall emotions of hurt, loss, judgment, and anger at their interface with health care during pregnancy. Providers described gaps in knowledge of substance use in pregnancy and harm reduction. Although care providers overall perceived themselves to be providing compassionate care without bias, the patient journey maps suggested profound judgment on behalf of providers. CONCLUSION: Ongoing cultural humility and trauma-informed care training along the continuum of care is critical to impacting discrepancies between perceived lack of bias and harm in patient interactions. Acknowledgment of systemic racism's impact on provision of maternity care is critical for health system change.

Highlighting strengths and resources that increase ownership of cervical cancer screening for Indigenous communities in Northern British Columbia: Community-driven approaches.

OBJECTIVE: To examine the unique and diverse strengths held by rural and remote Indigenous communities in northern British Columbia, including multi-generational support systems in health and wellness, profound connections to the land, and strong cultural foundations, and harness these strengths, allowing communities to engage in innovative and empowering health and wellness programs. METHODS: Building on these pre-existing and fundamental strengths, an alternative option to cervical cancer screening was introduced to nine Carrier Sekani health centers located in northern interior British Columbia in response to disparities in screening rates. Introduced in 2019, CervixCheck uses a self-collection approach that is private, safe, convenient, and offered at local community health centers by trained and supportive health staff. RESULTS: Using a strengths-based and community directed and descriptive approach, the process was outlined for a successful and ongoing health screening opportunity that is put into the hands of community members within Indigenous communities in the region of northern British Columbia. CONCLUSION: Through collaborative partnerships, in-person engagement sessions, and the utilization of pre-existing infrastructure and health and wellness teams, this project was successfully integrated into primary care centers using culturally safe and community-based approaches.

Acceptability and preferences for self-collected screening for cervical cancer within health systems in rural Uganda: A mixed-methods approach.

OBJECTIVE: To understand the knowledge, preferences, and barriers for self-collected cervical cancer screening (SC-CCS) and follow-up care at the individual and health system level to inform the implementation of community-based SC-CCS. METHODS: Surveys and focus group discussions (FGDs) with women and FGDs with healthcare providers were conducted in Uganda. Survey data were analyzed using frequencies and FGD data were analyzed using thematic content analysis. Data were triangulated between methods. RESULTS: Sixty-four women were surveyed and 58 participated in FGDs. Facilitators to screening access included decentralization, convenience, privacy, confidentiality, knowledge, and education. Barriers to accessing screening included lack of transportation and knowledge, long wait times, difficulty accessing health care, and lack of trust in the health system. Additional implementation challenges included insufficiently trained human resources and lack of infrastructure. CONCLUSION: Integrating SC-CCS within rural health systems in low-resource settings has been under-evaluated. Community-based SC-CSS could prevent high cervical cancer-related mortalities while working within the human and financial resource limitations of rural health systems. SC-CCS is acceptable to women and healthcare providers. By addressing rural women's preferences and barriers to care, decision-makers can build health systems that provide community-centered care close to women's homes across the care continuum.

Neonatal Abstinence Syndrome and Associated Neonatal and Maternal Mortality and Morbidity.

OBJECTIVES: We examined demographic characteristics and birth outcomes of infants with neonatal abstinence syndrome (NAS) and their mothers in Canada. METHODS: This retrospective, population-based, descriptive cross-sectional study of mother-infant dyads included all singleton live births in Canada (excluding Quebec), from 2005-2006 to 2015-2016 (N = 2 881 789). Demographic characteristics, NAS, and neonatal and maternal morbidities were identified from delivery hospitalization data (including diagnostic codes). The main composite outcomes were maternal and neonatal mortality and/or severe morbidity, including death and potentially life-threatening conditions in the mother and the infant, respectively. Logistic regression yielded adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: The study included 10 027 mother-infant dyads with NAS. The incidence of NAS increased from 0.20% to 0.51%. Maternal mortality was 1.99 vs 0.31 per 10 000 women in the NAS group versus the comparison group (aOR = 6.53; 95% CI: 1.59 to 26.74), and maternal mortality and/or severe morbidity rates were 3.10% vs 1.35% (aOR = 2.21; 95% CI: 1.97 to 2.49). Neonatal mortality was 0.12% vs 0.19% (aOR = 0.28; 95% CI: 0.15 to 0.53), and neonatal mortality and/or severe morbidity rates were 6.36% vs 1.73% (aOR = 2.27; 95% CI: 2.06 to 2.50) among infants with NAS versus without NAS. CONCLUSIONS: NAS incidence increased notably in Canada between 2005-2006 and 2015-2016. Infants with NAS had elevated severe morbidity, and their mothers had elevated mortality and severe morbidity. These results highlight the importance of implementing integrated care services to support the mother-infant dyad during childbirth and in the postpartum period.

Understanding Men's Perceptions of Human Papillomavirus and Cervical Cancer Screening in Kampala, Uganda.

PURPOSE: This preliminary study explores Ugandan men's knowledge and attitudes about human papillomavirus (HPV), cervical cancer, and screening. METHODS: A local physician led an education session about cervical cancer for 62 men in Kisenyi, Kampala in Uganda. Trained nurse midwives administered surveys to assess knowledge and attitudes before and after the education session. RESULTS: From the pre-education survey, only 24.6% of men had heard of HPV previously, and 59% of men had heard of cervical cancer. Posteducation, 54.5% of men believed only women could be infected with HPV and 32.7% of men believed antibiotics could cure HPV. Despite their limited knowledge, 98.2% of men stated they would support their partners to receive screening for cervical cancer, and 100% of men surveyed stated they would encourage their daughter to get the HPV vaccine if available. CONCLUSIONS: Knowledge of HPV and cervical cancer among Ugandan men is low. Even after targeted education, confusion remained about disease transmission and treatment. Ongoing education programs geared toward men and interventions to encourage spousal communication about reproductive health and shared decision making may improve awareness of cervical cancer prevention strategies.

Community-based HPV self-collection versus visual inspection with acetic acid in Uganda: a cost-effectiveness analysis of the ASPIRE trial.

BACKGROUND: Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. OBJECTIVE: Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women ('HPV-VIA') and (2) clinic-based VIA ('VIA'). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. DESIGN: We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy ('HPV-ST') involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. OUTCOME MEASURES: The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). RESULTS: HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%-4.7%) to 3.5% (range: 3.2%-4%), 2.8% (range: 2.4%-3.1%) and 2.4% (range: 2.1%-2.7%) with ICERs of US$130 (US$110-US$150) per YLS, US$240 (US$210-US$280) per YLS, and US$470 (US$410-US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. CONCLUSIONS: Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.