Implementation of new technologies designed to improve cervical cancer screening and completion of care in low-resource settings: a case study from the Proyecto Precancer.

BACKGROUND: This case study details the experience of the Proyecto Precancer in applying the Integrative Systems Praxis for Implementation Research (INSPIRE) methodology to guide the co-development, planning, implementation, adoption, and sustainment of new technologies and screening practices in a cervical cancer screening and management (CCSM) program in the Peruvian Amazon. We briefly describe the theoretical grounding of the INSPIRE framework, the phases of the INSPIRE process, the activities within each phase, and the RE-AIM outcomes used to evaluate program outcomes. METHODS: Proyecto Precancer iteratively engaged over 90 stakeholders in the Micro Red Iquitos Sur (MRIS) health network in the Amazonian region of Loreto, Perú, through the INSPIRE phases. INSPIRE is an integrative research methodology grounded in systems thinking, participatory action research, and implementation science frameworks such as the Consolidated Framework for Implementation Research. An interrupted time-series design with a mixed-methods RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework was used to examine the adoption of human papillomavirus (HPV) testing (including self-sampling), with direct treatment after visual inspection with portable thermal ablation, at the primary level. RESULTS: This approach, blending participatory action research, implementation science, and systems-thinking, led to rapid adoption and successful implementation of the new cervical cancer screening and management program within 6 months, using an HPV-based screen-and-treat strategy across 17 health facilities in one of the largest public health networks of the Peruvian Amazon. Monitoring and evaluation data revealed that, within 6 months, the MRIS had surpassed their monthly screening goals, tripling their original screening rate, with approximately 70% of HPV-positive women reaching a completion of care endpoint, compared with around 30% prior to the new CCSM strategy. CONCLUSIONS: Proyecto Precancer facilitated the adoption and sustainment of HPV testing with subsequent treatment of HPV-positive women (after visual inspection) using portable thermal ablation at the primary level. This was accompanied by the de-implementation of existing visual inspection-based screening strategies and colposcopy for routine precancer triage at the hospital level. This case study highlights how implementation science approaches were used to guide the sustained adoption of a new screen-and-treat strategy in the Peruvian Amazon, while facilitating de-implementation of older screening practices.

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2.

BACKGROUND: In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. OBJECTIVE: This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. STUDY DESIGN: We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF10-DEIA-LiPA25 system (DNA ELISA [enzyme-linked immunosorbent assay] HPV SPF10 kit and RHA HPV SPF10-LiPA25 kit). Persistence/progression was defined as having a record of cervical intraepithelial neoplasia grade ≥2 in the DPDB determined on the last and worst diagnosis on a biopsy or loop electrosurgical excision procedure specimen during follow-up. We estimated the relative risk (95% confidence interval) of persistence/progression using a modified Poisson model. RESULTS: A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. CONCLUSION: The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

"Easy women get it": pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program.

BACKGROUND: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system and community of a low-resource setting prior to implementation of an HPV screen-and-treat program. METHODS: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis. RESULTS: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism. CONCLUSIONS: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system and community in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.

Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study.

OBJECTIVE: To describe the long term risk of cervical cancer in women with untreated (that is, undergoing active surveillance) or immediately treated cervical intraepithelial neoplasia grade 2 (CIN2). DESIGN: Nationwide population based historical cohort study. SETTING: Danish healthcare registries. PARTICIPANTS: Women with CIN2 diagnosed in 1998-2020 and aged 18-40 years at diagnosis, who had either active surveillance or immediate treatment with large loop excision of the transformation zone (LLETZ). Women with a previous record of CIN2 or worse or LLETZ were excluded. MAIN OUTCOME MEASURE: A Weibull survival model for interval censored time-to-event data was used to estimate the cumulative risk of cervical cancer. Inverse probability treatment weighting was used to adjust estimates for age, index cytology, calendar year, and region of residence. RESULTS: The cohort included 27 524 women with CIN2, of whom 12 483 (45%) had active surveillance and 15 041 (55%) had immediate LLETZ. During follow-up, 104 cases of cervical cancer were identified-56 (54%) in the active surveillance group and 48 (46%) in the LLETZ group. The cumulative risk of cervical cancer was comparable across the two groups during the active surveillance period of two years. Thereafter, the risk increased in the active surveillance group, reaching 2.65% (95% confidence interval 2.07% to 3.23%) after 20 years, whereas it remained stable in the LLETZ group at 0.76% (0.58% to 0.95%). CONCLUSIONS: Undergoing active surveillance for CIN2, thereby leaving the lesion untreated, was associated with increased long term risk of cervical cancer compared with immediate LLETZ. These findings show the importance of continued follow-up of women having active surveillance.

"Easy women get it": Pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program.

Background: Cervical cancer is preventable with vaccination and early detection and treatment programs. However, in order for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system of a low-resource setting prior to implementation of an HPV screen-and-treat program. Methods: This study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis. Results: We identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women's HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism. Conclusions: Cervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention in Iquitos, Peru: a mixed methods study.

Background: Cervical cancer is a preventable cancer; however, decreasing its prevalence requires early detection and treatment strategies that reduce rates of loss to follow-up. This study explores factors associated with loss to follow-up among HPV-positive women after implementation of a screen-and-treat approach with visual triage and ablative therapy for cervical cancer prevention in Iquitos, Peru. Methods: We conducted semi-structured interviews with nurse-midwives (n = 15) working in cervical cancer prevention and women (n = 24) who were recorded as lost to follow-up after positive HPV results. We used the Health Care Access Barriers Model to guide analysis. We utilize manifest content analysis to describe barriers to follow-up according to the nurse-midwives and thematic analysis to report themes from the women's perspectives. We also report the steps and time taken to contact women and report discrepancies and concordances between nurse-midwives and women regarding reasons for loss to follow-up. Results: Women in this study expressed a desire to receive treatment. Barriers, including fragmented and incomplete registry systems, made receiving follow-up care more challenging. Nurse-midwives faced structural barriers in attempting to deliver positive results to women who were challenging to contact, and women did not have clear knowledge of how to receive their HPV results. Women faced cognitive barriers including a lack of understanding about HPV results and treatment procedures, fear or anxiety about HPV or treatment, and confusion about the follow-up process. Women also reported having important work matters as a barrier. Reported financial barriers were minimal. There was agreement between women's and nurse-midwives' reported barriers to follow-up in slightly over half of the cases. Conclusion: This study highlights the barriers to follow-up after implementation of a primary-level HPV-based screen-and-treat approach. While some barriers that have previously been associated with loss to follow-up were not observed in this study (e.g., financial), we emphasize the need for screen-and-treat programs to focus on strategies that can address incomplete registry systems, structural challenges in results delivery, cognitive barriers in understanding results and treatment, and work-related barriers.

Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study.

BACKGROUND: Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. OBJECTIVE: This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. STUDY DESIGN: This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. RESULTS: During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). CONCLUSION: The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

Implementation of new technologies designed to improve cervical cancer screening and completion of care in low-resource settings: A case study from the Proyecto Precancer.

Background: This case study details the experience of the Proyecto Precancer in applying the Integrative Systems Praxis for Implementation Research (INSPIRE) research methodology to guide the co-development, planning, implementation, adoption, and sustainment of new technologies and screening practices in a cervical cancer screening and management program in the Peruvian Amazon. We briefly describe the theoretical grounding of the INSPIRE framework, the phases of the INSPIRE process, the activities within each phase, and the RE-AIM outcomes used to evaluate program outcomes. Methods: Proyecto Precancer iteratively engaged over 90 stakeholders in the Micro Red Iquitos Sur (MRIS) health network in the Amazonian region of Loreto, Perú through the INSPIRE phases. INSPIRE is an integrative research methodology grounded in systems thinking, participatory action research, and implementation science frameworks such as the Consolidated Framework for Implementation Research. An interrupted time-series design with a mixed-methods RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework was used to examine the adoption of molecular-based primary cervical cancer screening using HPV-testing (including self-sampling), with direct treatment after visual inspection with portable thermal ablation at the primary level. Results: The participatory and system-thinking-oriented approach led to rapid adoption and successful implementation of the new cervical cancer screening and management program within 6 months, using an HPV-based screen-and-treat strategy across 17 health facilities in one of the largest public health networks of the Peruvian Amazon. Monitoring and evaluation data revealed that, within 6 months, the MRIS had surpassed their monthly screening goals, tripling their original screening rate, with approximately 70% of HPV-positive women reaching a completion of care endpoint, compared with around 30% prior to the new CCSM strategy. Conclusions: Proyecto Precancer facilitated the adoption and sustainment of molecular-based primary cervical cancer screening using HPV-testing (including self-sampling), with direct treatment after visual inspection with portable thermal ablation at the primary level and the de-implementation of existing visual inspection-based screening strategies and colposcopy for routine precancer triage at the hospital level. This case study shows how PP used implementation science approaches to guide the adoption of a new screen-and-treat strategy in the Peruvian Amazon, while facilitating de-implementation of older screening practices.

Redefining Expertise and Evidence in Global Implementation Research.

The theme for the 11th Annual Symposium on Global Cancer Research, co-convened with partners by the U.S. NCI Center for Global Health is "Closing the Research-to-Implementation Gap." Here, we reflect on the evolving role of implementation science from the lens of the needs of low- and middle-income countries. We highlight the importance for stronger and sustained engagement of implementation scientists and cancer control and prevention practitioners to enable more context-relevant co-design of implementation plans and strategies. We argue that deep learning from embedded implementation research through inductive analytic approaches is a critical first step to acceleration of evidence-to-practice translation and suggest an important role for systems approaches to facilitate this transition.

"Day or night, no matter what, I will go": Women's perspectives on challenges with follow-up care after cervical cancer screening in Iquitos, Peru: a qualitative study.

BACKGROUND: The study's objective was to explore the factors associated with loss to follow-up among women with abnormal cervical cancer screening results in Iquitos, Peru from women's perspectives. METHODS: In-depth interviews were conducted with 20 screen-positive women who were referred for follow-up care but for whom evidence of follow-up was not found. Interview transcripts were thematically analyzed inductively, and the codes were then categorized using the Health Care Access Barriers Model for presentation of results. RESULTS: All interviewed women were highly motivated to complete the continuum of care but faced numerous barriers along the way, including cognitive barriers such as a lack of knowledge about cervical cancer and poor communication from health professionals regarding the process, structural barriers such as challenges with scheduling appointments and unavailability of providers, and financial barriers including out-of-pocket payments and costs related to travel or missing days of work. With no information system tracking the continuum of care, we found fragmentation between primary and hospital-level care, and often, registration of women's follow-up care was missing altogether, preventing women from being able to receive proper care and providers from ensuring that women receive care and treatment as needed. CONCLUSIONS: The challenges elucidated demonstrate the complexity of implementing a successful cervical cancer prevention program and indicate a need for any such program to consider the perspectives of women to improve follow-up after a positive screening test.

Trends in Adolescent Human Papillomavirus Vaccination and Parental Hesitancy in the United States.

BACKGROUND: Human papillomavirus (HPV) vaccination coverage remains suboptimal in the United States, underscoring the importance of monitoring trends in vaccine hesitancy. METHODS: Cross-sectional data from the 2011-2020 National Immunization Survey-Teen were used to assess trends in HPV vaccination initiation among 13-17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy. RESULTS: Among all sex and race and ethnicity groups, the prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%). Among hesitant parents, "safety concerns" increased in nearly all demographic groups, with the greatest increases observed for non-Hispanic white female and male teens and no change for non-Hispanic black female teens. In 2019-2020, parents of unvaccinated non-Hispanic white teens were least likely to intend on vaccinating their teens, and the most common reason for hesitancy varied by sex and race and ethnicity (eg, "safety concerns" for white teens and "not necessary" for black female teens). CONCLUSIONS: Although HPV vaccination initiation increased over time, a substantial fraction of parents remain hesitant, and trends in their reason varied by sex and race and ethnicity. Health campaigns and clinicians should address vaccine safety and necessity.

Adolescent vaccination against human papillomavirus (HPV) is a critical tool for cancer prevention. We analyzed trends in HPV vaccination initiation among adolescents aged 13­17 years and trends in parental hesitancy to initiate HPV vaccination for their teen, using data from a national survey in the United States. Between 2011­2012 and 2019­2020, adolescent HPV vaccination initiation increased over time for both female teens (from 53.4% to 75.2%) and male teens (from 14.5% to 71.5%). However, the majority of parents/guardians of unvaccinated teens did not intend to vaccinate their teen against HPV (ie, were vaccine hesitant), and this was consistent over time in all sex and race and ethnicity groups. Among hesitant parents, the proportion reporting safety concerns as their main reason for being hesitant increased over time in nearly all demographic groups, with the greatest increases in this reasoning observed for white teens. In 2019­2020, parents of unvaccinated white teens were most likely to be vaccine hesitant. The most common reason for being vaccine hesitant also differed by sex and race and ethnicity. Although HPV vaccination has been shown to be safe and effective, HPV vaccination coverage remains suboptimal, and a substantial fraction of parents/guardians continue to be hesitant to adolescent HPV vaccination.

Women's perspectives on the acceptability and feasibility of an HPV screen-and-treat approach to cervical cancer prevention in Iquitos, Peru: a qualitative study.

BACKGROUND: The objective of this study was to explore women's experiences of a screen-and-treat approach with ablative therapy (referred to by the Spanish acronym TVT-TA) as a method of treatment following a positive HPV test in Iquitos, Peru. METHODS: A total of 111 in-depth interviews were conducted with 47 HPV positive women who attended the TVT-TA procedure at a primary-level healthcare facility. Interviews were conducted immediately before, immediately after, and six-weeks after TVT-TA. RESULTS: Most interviewed women reported experiencing moderate pain during ablative therapy and minimal pain immediately after and six weeks after ablative therapy. Women also stated that the pain was less intense than they had expected. The most common physical after-effects of treatment were bleeding and vaginal odor. Women experienced oscillating emotions with fear upon receiving a positive HPV result, calming after hearing about ablative therapy treatment, worry about pain from the treatment itself, relaxation with counseling about the procedure, and relief following treatment. CONCLUSIONS: Nearly all participants emphasized that they were pleased with the TVT-TA process even if they had experienced pain during TVT-TA, recommended that TVT-TA be expanded and available to more women, and stated that TVT-TA was faster and easier than expected. This study found that TVT-TA is a feasible and acceptable means of treating HPV according to the women receiving the treatment.

Performance of HPV E4 and p16INK4a biomarkers in predicting regression of cervical intraepithelial neoplasia grade 2 (CIN2): protocol for a historical cohort study.

INTRODUCTION: Cervical intraepithelial neoplasia grade 2 (CIN2) represents a spectrum of lesions with variable progression and regression. Pathological diagnosis of CIN2 is subjective and poorly reproducible. Accurate diagnosis and identification of different patterns of CIN2 related to outcome are essential to reduce the risks of overtreatment or undertreatment. It is important to explore novel methods for risk stratification of CIN2 to enable targeted treatment of women at high risk of progression or persistent disease and follow-up of women at low risk. The combination of the novel biomarker human papillomavirus (HPV) E4 with p16INK4a targets steps in the transition from a productive oncogenic HPV infection (CIN1) to a transformed lesion (CIN3) within CIN2. Previous cross-sectional studies suggest that HPV E4 combined with p16INK4a may be valuable for risk assessment of CIN2. However, data on HPV E4/p16INK4a as a predictor for CIN2 regression is lacking. METHODS AND ANALYSIS: We will conduct a historical cohort study including 500 women aged 23-40 years with a first CIN2 diagnosis in Aarhus, Denmark during 2000-2010. Women will be eligible if they have undergone active surveillance and have no previous record of hysterectomy, cone biopsy, and CIN2 or worse. Women will be randomly selected through the Danish Pathology Databank. Tissue samples from women included will be sectioned for p16INK4a and HPV E4 immunohistochemical staining in addition to conventional hematoxylin and eosin (H&E) staining. A positive result will be defined as HPV E4 positive. Through the Danish Pathology Databank, we will collect results on all subsequent cervical biopsies. Regression will be used as the primary outcome. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee in Central Denmark Region (1-10-72-60-20) and registered at the Faculty of Health, Aarhus University. Results will be published in a peer-reviewed journal and presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05049252.

Evidence of latent HPV infection in older Danish women with a previous history of cervical dysplasia.

INTRODUCTION: Understanding whether human papillomavirus (HPV) may establish latency in the uterine cervix is important. A better understanding of HPV natural history is useful for clinical counseling of women attending screening and to accurately inform health prevention strategies such as screening and HPV vaccination. We evaluated the extent of latent HPV infections in older women with a history of abnormal cytology. MATERIAL AND METHODS: We conducted a cross-sectional study in Aarhus, Denmark, from March 2013 through April 2015. Women were enrolled if they underwent cervical amputation or total hysterectomy because of benign disease. Prior to surgery, women completed a questionnaire and a cervical smear was collected for HPV testing and morphological assessment. For evaluation of latency (i.e., no evidence of active HPV infection, but HPV detected in the tissue), we selected women with a history of abnormal cervical cytology or histology, as these women were considered at increased risk of harboring a latent infection. Cervical tissue underwent extensive HPV testing using the SPF10-DEIA-LipA25 assay. RESULTS: Of 103 women enrolled, 26 were included in this analysis. Median age was 55 years (interquartile range [IQR] 52-65), and most women were postmenopausal and parous. The median number of sexual partners over the lifetime was six (IQR 3-10), and 85% reported no recent new sexual partner. Five women (19.2%) had evidence of active infection at the time of surgery, and 19 underwent latency evaluation. Of these, a latent infection was detected in 11 (57.9%), with HPV16 being the most prevalent type (50%). Nearly 80% (n = 14) of the 18 women with a history of previous low-grade or high-grade cytology with no treatment had an active or latent HPV infection, with latent infections predominating. HPV was detected in two of the six women with a history of high-grade cytology and subsequent excisional treatment, both as latent infections. CONCLUSIONS: HPV can be detected in cervical tissue specimens without any evidence of an active HPV infection, indicative of a latent, immunologically controlled infection. Modeling studies should consider including a latent state in their model when estimating the appropriate age to stop screening and when evaluating the impact of HPV vaccination.

Known Benefits and Unknown Risks of Active Surveillance of Cervical Intraepithelial Neoplasia Grade 2.

Cervical intraepithelial neoplasia grade 2 (CIN 2) is an equivocal diagnosis with high interobserver variation. Owing to high regression rates of 50%, many countries recommend active surveillance of CIN 2, especially in women younger than age 25-30 years, where regression rates are even higher (ie, 60%). Additionally, excisional treatment is associated with increased risk of reproductive harm, particularly preterm birth. Active surveillance typically consists of semi-annual follow-up visits for up to 2 years, including colposcopy and either cytology, testing for human papillomavirus, or both. Excisional treatment is recommended for progression or persistent disease after 2 years. Because active surveillance in younger women is relatively new, knowledge on subsequent risk of cervical cancer is limited. Considering human papillomavirus latency, women undergoing active surveillance might be at higher risk of cervical cancer than women undergoing excisional treatment. Furthermore, there are limited data describing preferences of women for the management of CIN 2, and it is also unclear how active surveillance may affect planning for future pregnancy. In this context, biomarkers for risk stratification of CIN 2 into either high or low probability of progression would allow for targeted treatment. Currently, immunohistochemical staining for p16 is used to clarify the histologic diagnosis, but whether it or other biomarkers can be used for risk-stratification in clinical management of women with CIN 2 remains unknown. In conclusion, active surveillance of CIN 2 needs further investigation, including understanding the long-term cervical cancer risk and evaluation of markers that may enable risk stratification of CIN 2.

Gut Helminth Infection-Induced Immunotolerance and Consequences for Human Papillomavirus Persistence.

Cervical cancer, a malignancy caused by persistent human papillomavirus (HPV) infection, develops in more than 500,000 women annually. More than 90% of deaths from cervical cancer occur in low- and middle-income countries. A common epidemiological feature of countries with high cervical cancer incidence is a high burden of intestinal helminth infection. The ability of intestinal helminths to trigger immunoregulation, resulting in a "tolerogenic" systemic immune environment, provides fertile soil for the persistence of oncogenic viruses such as HPV. Animal models have shown that intestinal helminth infection permits the persistence of some viruses, however, HPV-specific and human studies are lacking. Large, well-organized trials evaluating the consequences of intestinal helminth infection on the human immune system and HPV persistence may lead to improved strategies for HPV prevention in helminth-endemic regions of the world. Additionally, such studies would offer insight into the specific ways that intestinal helminth infection contributes to immunomodulation, which could identify new therapeutic targets for a range of diseases, from inflammatory disorders to cancer. In this review, we discuss the evidence for helminth-induced systemic and local immune dysregulation, discuss possible mechanisms by which chronic intestinal helminth infection may facilitate HPV persistence, and suggest novel helminth-related interventions that could offer a high leverage (if somewhat unconventional) approach to HPV and cervical cancer control in resource-constrained regions.

Burden of Mycoplasma genitalium and Bacterial Coinfections in a Population-Based Sample in New Mexico.

ABSTRACT: In this population-based US study, the overall prevalence of Mycoplasma genitalium was 1.95% (95% confidence interval [CI], 1.62%-2.34%), declining from 6.12% (95% CI, 4.72%-7.92%) in women aged 21 to 24 years to 0.48% (95% CI, 0.25%-0.94%) in women aged 40 to 64 years. The prevalence of coinfections with Chlamydia trachomatis and Trichomonas vaginalis was low.

Association of Vaginal Microbiota With Signs and Symptoms of the Genitourinary Syndrome of Menopause Across Reproductive Stages.

The genitourinary syndrome of menopause (GSM) describes signs and symptoms resulting from effects of estrogen deficiency on the female genitourinary tract, including the vagina, labia, urethra, and bladder. Signs/symptoms associated with GSM may occur during any reproductive stage from multiple etiologies but are most common during menopause due to low estrogen. Vaginal microbiota, particularly Lactobacillus spp., are beneficial to the female genital tract; however, their abundance declines during menopause. We aimed to longitudinally assess vaginal microbiota characterized by 16S rRNA gene amplicon sequencing and GSM-associated endpoints across reproductive stages. In a 2-year cohort study of 750 women aged 35-60 years at enrollment and 2 111 semiannual person-visits, low-Lactobacillus vaginal microbiota communities were observed at 21.2% (169/798), 22.9% (137/597), and 49.7% (356/716) of person-visits among pre-, peri-, and postmenopausal women, respectively (p < .001). Compared to communities that have high Gardnerella vaginalis relative abundance and diverse anaerobes, the following communities were associated with a lower covariate-adjusted odds of vaginal atrophy: L crispatus-dominated communities among postmenopausal women (odds ratio [OR] = 0.25; 95% confidence interval [CI]: 0.08, 0.81), L gasseri/L jensenii (OR = 0.21; 95% CI: 0.05, 0.94) and L iners (OR = 0.21; 95% CI: 0.05, 0.85) among perimenopausal women, and L iners-dominated communities (OR = 0.18; 95% CI: 0.04, 0.76) among premenopausal women. Postmenopausal women with L gasseri/L jensenii-dominated communities had the lowest odds of vaginal dryness (OR = 0.36; 95% CI: 0.12, 1.06) and low libido (OR = 0.28; 95% CI: 0.10, 0.74). Findings for urinary incontinence were inconsistent. Associations of vaginal microbiota with GSM signs/symptoms are most evident after menopause, suggesting an avenue for treatment and prevention.

Knowledge, attitudes, and practices of cervical cancer prevention and pap smears in two low-income communities in Lima, Peru.

BACKGROUND: Cervical cancer is a leading cause of death among Peruvian women. Barriers at multiple levels impact effective screening and treatment, including a lack of knowledge about cervical cancer and how regular screening can reduce morbidity and mortality through earlier detection. The aim of this study is to assess knowledge, attitudes, and practices regarding cervical cancer and its prevention in the peri-urban communities of Oasis and Pampas in southern Lima, Peru that can be used to inform future campaigns about cervical cancer prevention. METHODS: A cross-sectional survey that included several open-ended questions was administered to women in Pampas and Oasis between 2015 and 2016 to evaluate the knowledge, attitudes, and practices regarding cervical cancer and Pap smears. RESULTS: In total, 224 women were interviewed. Knowledge about cervical cancer and Pap smears was high, and attitudes were predominantly positive among most participants. Most participants knew how often they should get Pap smears (89.7%), when to begin seeking screening (74.6%), knew the price of a Pap smear (61.9%), and felt Pap smears were important for their health (70.1%). About one third (29.5%) of premenopausal women reported receiving a Pap smear in the last year. However, open ended questions revealed some knowledge gaps around Pap smears, as well as some stigma associated to Human Papilloma Virus (HPV) infection. CONCLUSION: Although knowledge of cervical cancer prevention was generally high and perceptions were positive among women in peri-urban Peruvian communities, our findings revealed there is a need for education on HPV infection prevalence among sexually active individuals to reduce stigma. Future research should focus on exploring experiences with follow-up and treatment associated with abnormal Pap smears, as well as perspectives from health authorities and professionals about barriers in the early detection and treatment process for cervical cancer.