Comparison of urine specimen collection times and testing fractions for the detection of high-risk human papillomavirus and high-grade cervical precancer

Background: Urine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. Objectives: We examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). Study design: A total of 37 female colposcopy clinic attendees, ≥30 years, provided three urine samples: "first void" urine collected at home, and "initial stream" and "mid-stream" urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. Results: HR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8-72.7%]) than in initial stream urine (75.7%[61.9-89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI. =. 62.7-99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1-96.6%]). Conclusion: This is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed

Preference for Human Papillomavirus Self-Collection and Papanicolaou: Survey of Underscreened Women in North Carolina

Objectives Self-collection of samples for human papillomavirus (HPV) testing (self-collection) has the potential to increase cervical cancer screening among underscreened women. We assessed attitudes toward at-home HPV self-collection compared with clinic-based Pap testing in this higher-risk population. Materials and Methods Participants were low-income women in North Carolina overdue for cervical cancer screening. Women self-collected samples at home, returned samples by mail for HPV testing, and completed phone questionnaires about at-home HPV self-collection. Participants were referred to clinic-based Pap testing and invited to complete a second questionnaire about Pap testing. A cross-sectional questionnaire compared attitudes, experiences, and preferences for self-collection versus Pap testing and assessed predictors of preference for HPV self-collection. Results Half (51%) of 221 women reported a preference for HPV self-collection, 19% preferred Pap testing, and 27% reported no preference. More women reported difficulty finding time to do the Pap test (31%) than the self-test (13%, p =.003) and being afraid of the self-test results (50%) than the Pap test results (36%, p =.02). There were relatively fewer reports of physical discomfort and pain from self-collection than Pap testing (discomfort: 18% self; 48% Pap; pain: 8% self; 30% Pap, p =.001). No differences were found in positive versus negative thoughts about the tests, trust in the tests' safety and accuracy, or willingness to do tests again. Conclusions Overall positive attitudes toward HPV self-collection compared with Pap testing among underscreened women suggest that self-collection is a promising option to increase cervical cancer screening in this high-risk population

Worldwide incidence of cervical lesions: a systematic review

We conducted a systematic review summarizing data on incidence of high- and low-grade lesions in women with normal baseline cervical cytology, stratified by age (<30 and ⩾30 years), and baseline human papillomavirus (HPV) infection. Incidence of high- and low-grade lesions in women aged ⩾30 years with a baseline HPV infection increased over follow-up time (5-127 months), although incidence generally remained <10%. Without baseline HPV infection, incidence of high-grade lesions remained low over follow-up time (<5% over 5-122 months). Incidence of high-grade lesions in women aged ⩾30 years with baseline HPV infection appeared similar to that in women aged <30 years. In some women aged <30 years, high-grade lesions can develop relatively shortly after initial HPV infection. We observed an increase in low-grade lesions over time in women aged ⩾30 years with baseline HPV infection, potentially indicative of an HPV infection that is potentially progressing to higher grade lesions

An overview of early investigational drugs for the treatment of human papilloma virus infection and associated dysplasia

Introduction: High-risk HPV (HR-HPV) related invasive cervical cancer (ICC) causes >270,000 deaths per annum world-wide with over 85% of these occurring in low-resource countries. Ablative and excisional treatment modalities are restricted for use with high-grade pre-cancerous cervical disease with HPV infection and low-grade dysplasia mostly managed by a watch-and-wait policy.Areas Covered: Various pharmacological approaches have been investigated as non-destructive alternatives for the treatment of HR-HPV infection and associated dysplasia. These are discussed dealing with efficacy, ease-of-use (physician or self-applied), systemic or locally applied, side-effects, cost and risks. The main focus is the perceived impact on current clinical practice of a self-applied, effective and safe pharmacological anti-HPV treatment.Expert opinion: Current prophylactic HPV vaccines are expensive, HPV type restricted and have little effect in already infected women. Therapeutic vaccines are under development but are also HPV type-restricted. At present, the developed nations use national cytology screening and surgical procedures to treat only women identified with HPV-related high-grade dysplastic disease. However, since HPV testing is rapidly replacing cytology as the test-of-choice, a suitable topically-applied and low-cost antiviral treatment could be an ideal solution for treatment of HPV infection per se with test-of-cure carried out by repeat HPV testing. Cytology would only then be necessary for women who remained HPV positive. Although of significant benefit in the developed countries, combining such a treatment with self-sampled HPV testing could revolutionise the management of this disease in the developing world which lack both the infrastructure and resources to establish national cytology screening programs

Evaluating situational judgment test use and diversity in admissions at a southern US medical school

Introduction Situational judgment tests have been adopted by medical schools to assess decision-making and ethical characteristics of applicants. These tests are hypothesized to positively affect diversity in admissions by serving as a noncognitive metric of evaluation. The purpose of this study was to evaluate the performance of the Computer-based Assessment for Sampling Personal Characteristics (CASPer) scores in relation to admissions interview evaluations. Methods This was a cohort study of applicants interviewing at a public school of medicine in the southeastern United States in 2018 and 2019. Applicants took the CASPer test prior to their interview day. In-person interviews consisted of a traditional interview and multiple-mini-interview (MMI) stations. Between subjects, analyses were used to compare scores from traditional interviews, MMIs, and CASPer across race, ethnicity, and gender. Results 1,237 applicants were interviewed (2018: n = 608; 2019: n = 629). Fifty-seven percent identified as female. Self-identified race/ethnicity included 758 White, 118 Black or African-American, 296 Asian, 20 Native American or Alaskan Native, 1 Native Hawaiian or Other Pacific Islander, and 44 No response; 87 applicants identified as Hispanic. Black or African-American, Native American or Alaskan Native, and Hispanic applicants had significantly lower CASPer scores than other applicants. Statistically significant differences in CASPer percentiles were identified for gender and race; however, between subjects, comparisons were not significant. Conclusions The CASPer test showed disparate scores across racial and ethnic groups in this cohort study and may not contribute to minimizing bias in medical school admissions

“There is nothing that can prevent me from supporting her:” men’s perspectives on their involvement and support of women’s use of topical therapy for cervical precancer treatment in Kenya

Purpose: Cervical cancer disproportionately impacts women in low- and middle-income countries (LMICs). The World Health Organization’s (WHO) 90/70/90 strategy aims to eliminate cervical cancer by 2030 by increasing HPV vaccination coverage to 90%, screening 70% of eligible women, and effectively treating 90% of those with abnormal results by 2030, potentially preventing 62 million deaths in LMICs. LMICs, however, struggle with limited access to cervical precancer treatment, in part due to a lack of trained professionals and weak health systems. Effective non-surgical, self-administered, which have demonstrated efficacy in high-income countries, could bridge the treatment gap in LMICs and may be more scalable and cost-effective than provider-administered therapies. To inform feasibility studies in LMICs, data are needed on the role of male partners in influencing the acceptability and uptake of self-administered topical therapies, including their support of recommended abstinence and contraception guidelines associated with these therapies. Methods: Between November 2022 and April 2023, we conducted five focus group discussions (FGDs) with men aged 25 to 65 years in Kenya to explore their perspective and perceived support regarding their female partners using topical self-administered therapies for cervical precancer treatment. The FGDs were moderated by local qualitative research assistants and conducted in local languages, transcribed, coded, and analyzed using qualitative description. Results: Thirty-nine male participants meeting the eligibility criteria participated in five FGDs. The mean age of participants was 42.5 years. Most participants, 79.5%, had a female partner with a history of cervical precancer treatment, 5.1% did not, and 15.4% were unsure of their female partner’s prior precancer treatment history. The study aimed to assess men’s support of their female partners’ use of topical therapies for treating cervical precancer. We find that male participants strongly express acceptance and willingness to support their wives or partners in using such therapies, if available. Reported supportive behavior included permitting the use of the therapies and support of maintaining abstinence during the recommended times. Additionally, participants desired male involvement in clinic and community-based education about topical therapies to facilitate widespread support. Conclusion: The use of self-administered topical therapies for cervical precancer treatment, if supported by efficacy studies in LMICs, may support achieving the WHO’s 2030 goal of 90% treatment access. We find that with adequate education, men express overwhelming support of their female partner’s use of topical therapies, including adherence to abstinence and contraception guidelines

Postpartum HIV care continuum outcomes in the southeastern USA

The aim of this study was to evaluate postpartum HIV care outcomes.Design:A prospective clinical cohort of women with HIV and a live birth at the University of North Carolina, 1996-2014.Methods:We estimated two stages of the HIV care continuum in the first 24 months postpartum: care retention (at least two visits per year, ≥90 days apart) and viral suppression (HIV RNA<400copies/ml). Multivariable models were fit using logistic regression.Results:Among 1416 women, 141 experienced a live birth at a median age of 28 years, with 74% virally suppressed at delivery. Among all women, 48% were retained in care and 25% maintained viral suppression for the first 24 months postpartum. Among women with available HIV RNA measures, 42% were suppressed at 24 months. HIV care retention estimates were stable across calendar years, but viral suppression rates at 24 months postpartum, among women with available HIV RNA measures, increased from 33 to 67% from 1996-2001 to 2009-2014 (P=0.04). Being at least 30 years old was positively, and receiving less than 12 weeks of antenatal antiretroviral therapy was negatively, associated with HIV care retention at 24 months postpartum [adjusted odds ratio (AOR): 2.41, 95% confidence interval (95% CI): 1.09-5.29 and AOR: 0.27, 95% CI: 0.08-0.86]. Older maternal age and viral suppression at delivery were both positively associated with virologic suppression at 24 months postpartum (AOR: 2.52, CI: 1.02-6.22, and AOR: 6.42 CI: 1.29-31.97, respectively).Conclusion:HIV care continuum outcomes decrease substantially postpartum, with younger women and those with less antenatal HIV care less likely to successfully remain engaged in HIV care following childbirth

A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction

Minimizing time to Human Immunodeficiency Virus (HIV) viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV ribonucleic acid (RNA) in nonpregnant adults. There is limited data in pregnant women

Test accuracy of human papillomavirus in urine for detection of cervical intraepithelial neoplasia

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or <CIN2. We calculated the sensitivity and specificity for detection of CIN2+ and assessed agreement between sample collection methods. We included 307 women (median age, 36 years) with valid histology results and triplematched urine, self-collected cervicovaginal, and provider-collected cervical hrHPV results; 83 women (27%) had CIN2+. Urine-based hrHPV testing correctly identified 80% of CIN2+ cases (95% confidence interval [CI], 71 to 88%) using the PCR cycle threshold (CT) established for provider-collected cervical samples, but sensitivity remained below the estimates for self-collected cervicovaginal and provider-collected cervical samples (both 94% [95% CI, 89 to 99%]). Using a higher CT cutoff value of ≤40, 90% sensitivity was achieved for urine-based hrHPV testing. Agreement between results for urine samples and self-collected cervicovaginal samples (kappa = 0.58) or provider-collected cervical samples (kappa = 0.54) was moderate. Urinebased hrHPV testing may be a promising approach to improve cervical cancer screening coverage, especially among women with limited access to health care