Topical Imiquimod for the Treatment of High-Grade Squamous Intraepithelial Lesions of the Cervix: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the histologic response rate of high-grade squamous intraepithelial lesions (HSIL) of the cervix after topical application of 5% imiquimod cream. METHODS: In this phase II trial, women with cervical HSIL (cervical intraepithelial neoplasia [CIN] 2-3) were randomly assigned to 250 mg of 5% imiquimod cream applied to the cervix weekly for 12 weeks, followed by loop electrosurgical excision procedure (LEEP) without preceding treatment. The sample size was calculated based on the HSIL regression rates previously reported by Grimm et al. The primary outcome was rate of histologic regression (to CIN 1 or less) in LEEP specimens. Prespecified secondary endpoints included surgical margin status and adverse events. Outcomes were stratified by human papillomavirus type and lesion grade (CIN 2 or CIN 3). Results were reported according to per protocol (PP) and intention-to-treat (ITT) analyses. RESULTS: Ninety women were enrolled: 49 in the experimental group and 41 in the control group. In the PP population, histologic regression was observed in 23 of 38 participants (61%) in the experimental group compared with 9 of 40 (23%) in the control group (P=.001). Surgical margins were negative for HSIL in 36 of 38 participants (95%) in the experimental group and 28 of 40 (70%) in the control group (P=.004). In the ITT population, rates of histologic regression also were significantly higher in the experimental group. Rates of adverse events in the experimental group were 74% (28/38) in the PP population and 78% (35/45) in the ITT population. Adverse events were mild, with abdominal pain being the most common. Three patients in the experimental group had grade 2 adverse events, including vaginal ulcer, vaginal pruritus with local edema, and moderate pelvic pain. CONCLUSION: Weekly topical treatment with imiquimod is effective in promoting regression of cervical HSIL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03233412.

Evaluation of human papillomavirus self-collection offered by community health workers at home visits among under-screened women in Brazil.

OBJECTIVE: To explore the acceptability of high-risk human papillomavirus self-testing, involving community health workers, for never/under-screened Brazilian women. Cervical cancer is the most common cause of cancer-related death among adult women in a large number of low-income and lower-middle-income countries, where it remains a major public health problem. High-risk human papillomavirus persistence is required for the development of cervical neoplasia. METHODS: The target population was all women aged 30+ from the list of families available in healthcare centre data, who had never been screened or were not screened in the previous 3 years (under-screened women), and who were living in the 17 cities included in this study. RESULTS: Of the 377 women included, 16.9% (n = 64) had never had a pap smear. Of all samples included in the study, 97.1% (n = 366) were considered adequate for evaluation, as 2.9% (n = 11) were considered invalid for all high-risk human papillomavirus types. Analysing these 366 samples, 9.6% (n = 35) of the women were infected by at least one high-risk human papillomavirus type and 90.4% (n = 331) had no infection with any high-risk type of the virus. CONCLUSIONS: Vaginal self-sampling is an adequate strategy to improve the effectiveness of the cervical cancer program by increasing screening in a high-risk group.

Detection of HPV E6 oncoprotein from urine via a novel immunochromatographic assay.

Cervical cancer is a significant public health problem, especially in low- and middle-income countries, where women have little access to cervical cancer screening; consequently 80% of cervical cancer related mortality occurs in these regions. The development of screening methods that need less infrastructure thus represents an urgent medical need. The study aims to compare the detection rates of high-risk human papillomavirus 16 and 18 E6 oncoprotein in urine, vaginal self-collected, and cervical scrapes of women using the OncoE6™ Cervical Test and compare the HPV16 and/or HPV18 E6 detection rates with the HPV DNA testing. Paired urine, vaginal self-collected and cervical specimens were collected from 124 women who participated in cervical cancer screening or treatment in this proof-of-concept study and underwent to HPV16/18-E6 testing and high-risk HPV DNA testing prior to treatment of cervical neoplasia or cancer. Concordance between urinary, vaginal and cervical HPV16/18-E6 and HPV-DNA testing was evaluated for patients classified as negative group (

Is Proflavine Exposure Associated with Disease Progression in Women with Cervical Dysplasia? A Brief Report.

Proflavine is an acridine dye used with high-resolution microendoscopy for in vivo diagnostic evaluation of cervical epithelial cells. However, there are concerns that even short-term exposure of cervical tissue to dilute proflavine may increase cervical cancer risk. We performed a retrospective analysis of women referred for colposcopy to Barretos Cancer Hospital comparing the risk of cervical disease progression in those whose cervical tissue was (n = 232) or was not exposed (n = 160) to proflavine. Patients in both groups underwent treatment and follow-up based on histopathologic results and per the local standards of care. Progression of disease was evaluated by comparing histopathology from the initial visit to the worst subsequent histopathology result from all follow-up visits. Mean duration of follow-up was 18.7 and 20.1 months for the proflavine-exposed and controls groups, respectively. There were no significant differences in disease progression from normal/CIN1 to CIN2/3 or from any initial diagnosis to invasive cancer between the proflavine exposed and control groups overall. Risks of cervical dysplasia progression observed in this study are in agreement with those of the natural history of cervical cancer. Our results suggest that cervical exposure to dilute proflavine does not increase the risk of cervical precancer and cancer.

Development and validation of a prognostic nomogram for ambulatory patients with advanced cancer.

Predicting survival of advanced cancer patients (ACPs) is a difficult task. We aimed at developing and testing a new prognostic tool in ACPs when they were first referred to palliative care (PC). A total of 497 patients were analyzed in this study (development sample, n = 221; validation sample, n = 276). From 35 initial putative prognostic variables, 14 of them were selected for multivariable Cox regression analyses; the most accurate final model was identified by backward variable elimination. Parameters were built into a nomogram to estimate the probability of patient survival at 30, 90, and 180 days. Calibration and discrimination properties of the Barretos Prognostic Nomogram (BPN) were evaluated in the validation phase of the study. The BPN was composed of 5 parameters: sex, presence of distant metastasis, Karnofsky Performance Status (KPS), white blood cell (WBC) count, and serum albumin concentration. The C-index was 0.71. The values of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were 0.84, 0.74, and 0.74 at 30, 90, and 180 days, respectively. There were good calibration results according to the Hosmer-Lemeshow test. The median survival times were 313, 129, and 37 days for the BPN scores <25th percentile (<125), 25th to 75th percentile (125-175), and >75th percentile (>175), respectively (P < .001). The BPN is a new prognostic tool with adequate calibration and discrimination properties. It is now available to assist oncologists and palliative care physicians in estimating the survival of adult patients with advanced solid tumors.

Diagnosing Cervical Neoplasia in Rural Brazil Using a Mobile Van Equipped with In Vivo Microscopy: A Cluster-Randomized Community Trial.

Cervical cancer is a leading cause of death in underserved areas of Brazil. This prospective randomized trial involved 200 women in southern/central Brazil with abnormal Papanicolaou tests. Participants were randomized by geographic cluster and referred for diagnostic evaluation either at a mobile van upon its scheduled visit to their local community, or at a central hospital. Participants in both arms underwent colposcopy, in vivo microscopy, and cervical biopsies. We compared rates of diagnostic follow-up completion between study arms, and also evaluated the diagnostic performance of in vivo microscopy compared with colposcopy. There was a 23% absolute and 37% relative increase in diagnostic follow-up completion rates for patients referred to the mobile van (102/117, 87%) compared with the central hospital (53/83, 64%; P = 0.0001; risk ratio = 1.37, 95% CI, 1.14-1.63). In 229 cervical sites in 144 patients, colposcopic examination identified sites diagnosed as cervical intraepithelial neoplasia grade 2 or more severe (CIN2+; 85 sites) with a sensitivity of 94% (95% CI, 87%-98%) and specificity of 50% (95% CI, 42%-58%). In vivo microscopy with real-time automated image analysis identified CIN2+ with a sensitivity of 92% (95% CI, 84%-97%) and specificity of 48% (95% CI, 40%-56%). Women referred to the mobile van were more likely to complete their diagnostic follow-up compared with those referred to a central hospital, without compromise in clinical care. In vivo microscopy in a mobile van provides automated diagnostic imaging with sensitivity and specificity similar to colposcopy. Cancer Prev Res; 11(6); 359-70. ©2018 AACR.

Racial/Ethnic Disparities in Cervical Cancer Screening and Outcomes.

Invasive cervical cancer disproportionately affects women without sufficient access to care, with higher rates among minority groups in higher-income countries and women in low-resource regions of the world. Many elements contribute to racial/ethnic disparities in the cervical cancer continuum - from screening and diagnosis to treatment and outcome. Sociodemographic factors, access to healthcare, income and education level, and disease stage at diagnosis are closely linked to such inequities. Despite the identification of such elements, racial/ethnic disparities persist, and are widening in several minority subgroups, particularly in older women, who are ineligible for human papillomavirus (HPV) vaccination and are underscreened. Recent studies suggest that racial/ethnic differences in HPV infection exist and may also have a role in observed differences in cervical cancer. In this review, we provide an overview of the current literature on racial disparities in cervical cancer screening, incidence, treatment and outcome to inform future strategies to reduce persistent inequities.

Validation of the Modified Glasgow Prognostic Score in Advanced Cancer Patients Receiving Palliative Care.

CONTEXT: The modified Glasgow Prognostic Score (mGPS) is a well-known marker of systemic inflammatory response previously associated with poor prognoses in cancer. OBJECTIVES: We investigated the relationships between mGPS and clinical variables and the prognostic impact of mGPS in patients with advanced cancer starting palliative care (PC). METHODS: Data from two prospective studies conducted at a tertiary cancer center were analyzed (N = 459). Data regarding patient characteristics, Karnofsky Performance Status, and blood samples were collected at the initial evaluation. The mGPS was calculated as follows: C-reactive protein (CRP) < 10 mg/L = 0; CRP > 10 mg/L = 1, CRP > 10 mg/L and albumin < 35 g/L = 2. Chi-square or Fisher exact tests were used for comparisons of categorical variables; continuous variables were compared using the Mann-Whitney U test. For the survival analysis, Cox regression analyses were performed. RESULTS: mGPS of 0, 1, and 2 were assigned to 79.7%, 6.8%, and 13.5% of the patients, respectively. A positive association between hepatic metastasis (P = 0.004), primary lung cancer (P = 0.021), PC only (P < 0.001), lower Karnofsky Performance Status (P < 0.001), and higher systemic inflammation (mGPS 1/2) was found. Median overall survival was 1, 3, and 5.7 months for mGPS of 2, 1, and 0, respectively. After multivariate analyses, mGPS remained an independent prognostic marker (mGPS 1, hazard ratio 2.066, P = 0.001; mGPS 2, hazard ratio 2.664, P < 0.001). CONCLUSION: Systemic inflammatory response is associated with a low functional status, primary lung cancers, and tumors with hepatic metastasis. When starting PC, an mGPS definition may have clinical utility implications, by identifying three groups of patients with advanced cancer patients with distinct survival outcomes.