Investigator
Yale University
Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147)
Abstract Purpose: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients. Patients and Methods: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less. Secondary outcomes were HPV clearance and tolerability. Exploratory objectives included the comparison of cervical CD4/CD8 T-cell infiltration at baseline, mid-study, and posttreatment by flow cytometry among study arms. Results: Of the 114 evaluable patients 77% and 23% harbored CIN2 and CIN3, respectively. Regression to CIN1 or less was observed in 95% of patients in the imiquimod group (Arm B) compared with 79% in the control/surveillance (Arm A); P = 0.043 and 84% in the imiquimod+9vHPV group (Arm C; P = 0.384 vs. Arm A). Neither of the treatment-arm differences from Arm A reached the prespecified α = 0.025 significance level. No significant differences were noted in the secondary outcome of rate of HPV clearance. The number of tissue-resident memory CD4/CD8 T cells in cytobrush samples demonstrated a >5-fold increase in Arm B/imiquimod when compared with Arm A/surveillance (P < 0.01). In contrast, there was no significant difference in T-cell responses among participants in Arm C when compared with Arm A. Imiquimod treatment was well tolerated. Conclusions: Although imiquimod induced a higher regression to CIN1 or less and significant increases in CD4/CD8 T cells infiltrating the cervix, it did not meet its prespecified statistical outcome for efficacy. A higher regression rate than expected was observed in the surveillance arm of this prospective trial. Future clinical trials with imiquimod targeting CIN3 patients are warranted.
Association between cancer stigma and cervical cancer screening uptake among women of Dhulikhel and Banepa, Nepal
Background Cervical cancer ranks as the most common cancer among Nepalese women with a high incidence and mortality. Despite evidence that effective screening programs reduce disease burden, screening services are under-utilized. Cancer stigma can be a major barrier to cervical cancer screening uptake among Nepalese women. Objectives This study assessed the association between cancer stigma and cervical cancer screening uptake among women residing in semi-urban areas of Kavrepalanchok district (Dhulikhel and Banepa), Nepal. Methods We conducted a cross-sectional study among 426 women aged 30–60 years using telephone interview method from 15th June to 15th October 2021. A validated Cancer Stigma Scale (CASS) was used to measure cancer stigma and categorized women as presence of cancer stigma if the mean total score was greater than three. We obtained information on cervical cancer screening uptake through self-reported responses. Univariable and multivariable logistic regression were performed to assess the association between cancer stigma and cervical cancer screening uptake. We adjusted socio-demographic: age, ethnicity, occupation, religion and education, and reproductive health variables: parity, family planning user, age of menarche and age at first sexual intercourse during multivariable logistic regression. Results Twenty-three percent of women had cancer stigma and 27 percent reported that they had ever been screened for cervical cancer. The odds of being screened was 0.23 times lower among women who had stigma compared to those who had no stigma (95% CI: 0.11–0.49) after adjusting for confounders: age, ethnicity, occupation, religion, education, parity, contraceptive use, age of menarche and age at first sexual intercourse. Conclusion Women residing in semi-urban areas of Nepal and had cancer stigma were less likely to have been screened for cervical cancer. De-stigmatizing interventions may alleviate cancer stigma and contribute to higher uptake of cervical cancer screening.
Factors Associated With Timely Receipt of Colposcopy After Abnormal Cervical Cancer Screening
Objective The aim of the study was to examine factors associated with timely colposcopy following abnormal cervical cancer screening among patients receiving care at an urban safety-net obstetrics and gynecology clinic. Methods In this cohort study, the authors reviewed the care cycle of index abnormal cervical cancer screening requiring colposcopy follow-up from 3 separate years: 2016, 2018, and 2021. Primary outcomes included colposcopy attendance and timely colposcopy evaluation based on established guidelines. Multivariable log binomial regression models were used to evaluate patient characteristics and outcomes. Results Across the 3 years, the authors identified 820 abnormal cervical cancer screening results from 752 patients for which a colposcopy was indicated. Of these patients, 42.2% identified as non-Hispanic Black, 79.7% were English-speaking, and 80.0% were publicly insured. Pap tests requiring colposcopy resulted in completion 85.2% of the time, with 59.8% completed within guideline-concordant intervals. Human papillomavirus–vaccinated patients were less likely to attend colposcopy (relative risk [RR] = 0.84, 95% confidence interval [CI] = 0.76–0.93). Current smokers had lower colposcopy attendance compared to never-smokers (RR = 0.89, 95% CI = 0.81–0.98). Timely colposcopy took place 59.6% of the time in 2016, 56.9% of the time in 2018, and 63.3% of the time in 2021. Patients aged 40–49 and 50–64 were more likely to complete colposcopy within guideline recommended intervals than those younger than age 30 (RR = 1.23, 95% CI = 1.03–1.47; RR = 1.38, 95% CI = 1.15–1.66). Conclusions Despite modest overall improvement in the rate of guideline-concordant colposcopy attendance, significant gaps in timely follow-up persist. Targeted interventions are needed to improve follow-up care, particularly for younger patients and smokers.
