RESUMEN
Background: Carrageenan demonstrated potent anti-HPV (human papillomavirus) activity in vitro and in animal models. The Carrageenan-gel Against Transmission of Cervical Human papillomavirus trial's interim analysis (n = 277) demonstrated a 36% protective effect of carrageenan against incident HPV infections. Herein, we report the trial's final results. Methods: In this exploratory phase IIB randomised, placebo-controlled trial, we recruited healthy women aged ≥18 years primarily from health service clinics at two Canadian Universities in Montreal. Participants were randomised (1:1) by the study coordinator (using computer-assisted block randomisation with randomly variable block sizes up to a block size of eight) to a carrageenan-based or placebo gel to be self-applied every other day for the first month and before/after intercourse. Participants, study nurses, and laboratory technicians (HPV testing and genotyping) were blinded to group assignment. At each visit (months 0, 0.5, 1, 3, 6, 9, 12), participants provided questionnaire data and a self-collected vaginal sample (tested for 36 HPV types, Linear Array). The primary outcome was type-specific HPV incidence (occurring at any follow-up visit). Intention-to-treat analyses for incidence were conducted using Cox proportional hazards regression models, including participants with ≥2 visits. Safety analyses included all participants randomised. This trial is registered with the ISRCTN registry, ISRCTN96104919. Findings: Between Jan 16, 2013 and Sept 30, 2020, 461 participants (enrolled) were randomly assigned to the carrageenan (n = 227) or placebo (n = 234) groups. Incidence and safety analyses included 429 and 461 participants, respectively. We found 51.9% (108/208) of participants in carrageenan and 66.5% (147/221) in placebo arm acquired ≥1 HPV type (hazard ratio 0.63 [95% CI: 0.49-0.81], p = 0.0003). Adverse events were reported by 34.8% (79/227) and 39.7% (93/234) of participants in carrageenan and placebo arm (p = 0.27), respectively. Interpretation: Consistent with the interim analysis, use of a carrageenan-based gel compared to placebo resulted in a 37% reduction in risk of incident genital HPV infections in women with no increase in adverse events. A carrageenan-based gel may complement HPV vaccination. Funding: Canadian Institutes of Health Research, CarraShield Labs Inc.
RESUMEN
Background: The coronavirus disease 2019 (COVID-19) pandemic has caused disruptions to cancer care by delaying diagnoses and treatment, presenting challenges and uncertainties for both patients and physicians. We conducted a nationwide online survey to investigate the effects of the pandemic and capture modifications, prompted by pandemic-related control measures, on cervical cancer screening-related activities from mid-March to mid-August 2020, across Canada. Methods: The survey consisted of 61 questions related to the continuum of care in cervical cancer screening and treatment: appointment scheduling, tests, colposcopy, follow-up, treatment of pre-cancerous lesions/cancer, and telemedicine. We piloted the survey with 21 Canadian experts in cervical cancer prevention and care. We partnered with the Society of Canadian Colposcopists, Society of Gynecologic Oncology of Canada, Canadian Association of Pathologists, and Society of Obstetricians and Gynecologists of Canada, which distributed the survey to their members via email. We reached out to family physicians and nurse practitioners via MDBriefCase. The survey was also posted on McGill Channels (Department of Family Medicine News and Events) and social media platforms. The data were analyzed descriptively. Results: Unique responses were collected from 510 participants (November 16, 2020, to February 28, 2021), representing 418 fully and 92 partially completed surveys. Responses were from Ontario (41.0%), British Columbia (21.0%), and Alberta (12.8%), and mostly comprised family physicians/general practitioners (43.7%), and gynecologist/obstetrician professionals (21.6%). Cancelled screening appointments were mainly reported by family physicians/general practitioners (28.3%), followed by gynecologist/obstetrician professionals (19.8%), and primarily occurred in private clinics (30.5%). Decreases in the number of screening Pap tests and colposcopy procedures were consistently observed across Canadian provinces. About 90% reported that their practice/institution adopted telemedicine to communicate with patients. Conclusions: The area most severely impacted by the pandemic was appointment scheduling, with an important level of cancellations reported. Survey results may inform resumptions of various fronts in cervical cancer screening and management. Funding: The present work was supported by the Canadian Institutes of Health Research (operating grant COVID-19 May 2020 Rapid Research Funding Opportunity VR5-172666 Rapid Research competition and foundation grant 143347 to Eduardo L Franco). Eliya Farah and Rami Ali each received an MSc stipend from the Department of Oncology, McGill University.
Cervical cancer is a common cancer among women caused by infections with certain types of human papillomavirus (HPV). Nearly four in five people are infected with HPV during their lifetime, making it the most common sexually transmitted infection worldwide. Vaccination against the virus can prevent infections and routine screening for precancerous lesions can enable early diagnosis and treatment, improving outcomes. However, the COVID-19 pandemic has disrupted routine cervical cancer screening programs in several countries. This has caused delays in screening, which could result in more women being diagnosed with advanced-stage cancers. El-Zein et al. showed that despite the interrupted screening programmes, about half of practices in Canada were able to catch up on delayed screening by February 2021. Between November 2020 and February 2021, El-Zein et al. surveyed 510 Canadian healthcare professionals involved in cervical cancer screening and treatment. About 64%-75% of the respondents reported canceled or postponed screening appointments. Most appointment delays were less than four months. Fewer than one in ten delays were longer than six months. Most survey respondents said their practices pivoted to using telemedicine for some patient visits, such as cervical cancer screening follow-ups. About 40% of respondents suggested that the pandemic provided support to alternative screening options, such as HPV self-sampling at home. The survey results may help healthcare professionals and policymakers to develop plans that mitigate disruptions to cervical cancer screening during future emergencies.