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.

Challenges associated with follow-up care after implementation of an HPV screen-and-treat program with ablative therapy for cervical cancer prevention.

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 new HPV-based screen-and-treat approach for cervical cancer prevention in Iquitos, Peru. METHODS: We conducted semi-structured interviews with "obstetras" (i.e., 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 analyses. We utilized manifest content analysis to describe barriers to follow-up according to the obstetras and thematic analysis to report themes from the women's perspectives. We also report the steps and time taken to contact women. RESULTS: We found an incomplete and fragmented patient monitoring system. This incomplete system, in conjunction with challenges in contacting some of the women, led to structural barriers for the obstetras when attempting to deliver positive results. Women in this study expressed a desire to receive treatment, however, 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 and reported frequently using natural medicine. Reported financial barriers were minimal. 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 as prominently 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.

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.

Barriers and innovative interventions for early detection of cervical cancer / Barreras e intervenciones innovadoras para la detección temprana del cáncer cervicouterino

Abstract: Cervical cancer has decreased significantly over the past 30 years in some countries. However, it remains among the leading causes of cancer deaths in low-income, and racial/ethnic minority women. Cervical cancer prevention technologies are not always available. Laboratories are often not well equipped to use them. HPV information has not been widely disseminated. WHO guidelines, and US and Latin American data provide context for strategies on effective interventions to reduce cervical cancer disparities. Systemic, personal and cultural barriers, combined with decision-making guidelines, and impactful messaging can accelerate reductions in cervical cancer health inequities in the Americas.

Resumen: El cáncer cervicouterino ha disminuido significativamente en los últimos 30 años, pero sigue siendo una de las principales causas de muerte entre mujeres de bajos recursos y minorías raciales/étnicas. Las tecnologías preventivas del cáncer cervicouterino no están siempre disponibles y los laboratorios no están siempre bien equipados para utilizarlas. La información sobre el VPH no ha sido difundida ampliamente. La OMS y datos de EEUU y Latinoamérica ofrecen estrategias para reducir el cáncer cervicouterino. El entendimiento de las barreras sistémicas, personales y culturales, dentro de un marco de toma de decisiones, y mensajes innovadores puede reducir las barreras asociadas con el cáncer cervicouterino en las Américas.