Secondary prevention of cervical cancer in low- and middle-income countries.

Taghavi, Katayoun (2021). Secondary prevention of cervical cancer in low- and middle-income countries. (Unpublished). (Dissertation, University of Bern, Faculty of Medicine, Faculty of Science and Vetsuisse Faculty)

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With early and effective treatment of precancerous cervical lesions, cervical cancer can be prevented. Many countries that have implemented cervical cancer screening have observed a substantial reduction in cervical cancer-related morbidity and mortality over the last decades. However, vast geographic and socioeconomic disparities exist today, with most cervical cancers and deaths occurring in low- and middle-income countries (LMIC). Especially in countries with a high prevalence of human immunodeficiency virus (HIV), cervical cancer remains the leading cause of cancer-related death among women.

In May 2018, the World Health Organization (WHO) called for the elimination of cervical cancer (defined as an incidence rate of 4 per 100 000 women-years) and identified human papillomavirus (HPV) vaccination, screening, and treatment targets to achieve this. Mathematical modeling studies have shown that cervical cancer can be eliminated by highly resourced, well-organized screening programs, and HPV vaccination. A major scale-up of the screening programs is required to reach the WHO targets in LMIC. However, screening strategies that have successfully reduced the incidence of cervical cancer in some high-income countries cannot be replicated in LMIC and, as such, context-specific strategies are essential.

In my thesis, I used different study designs to increase understanding on the secondary prevention of cervical cancer in LMIC and women living with HIV (WLHIV).

Observational cohort studies
Specifically, studies 1 and 2 (Chapter 3.1 and 3.2, respectively) are cohort studies evaluating routinely collected data from visual inspection after application of acetic acid (VIA)-based screening programs in Zambia and Zimbabwe, respectively. Study 1 (Chapter 3.1) summarized cervical screening data from all 11 government health facilities in Lusaka, Zambia that provided cervical cancer screening services between January 2010 and July 2019. We assessed screening frequency, examined predictors of positive screening results, and described patterns of sensitization strategies according to age group and HIV status. Study 2 (Chapter 3.2) summarized data gathered from an antiretroviral clinic (ART) clinic with on-site cervical cancer screening capacity. We included 1624 women who had their first ART clinic appointment between 2012 and 2017 and also included the one-year follow-up appointment, taking the follow-up period to 2018. In this cohort study we present essential screening stages in terms of a secondary cervical cancer prevention cascade with two arms: screening and preventative treatment. In doing so, we have explored how women in ART clinics transitioned through linked stages of cervical cancer screening.

We found that in both study populations, screening frequency increased over time. In study 1 (Chapter 3.1) screening frequency increased 65.7% from 2010 to 2019. Furthermore, in study 2 (Chapter 3.2) we found that women who enrolled into care between 2015 and 2018 were more likely to complete the cervical cancer screening cascade than women who enrolled between 2012 and 2015 (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.16–1.49). The cascade analysis identified two important gaps in the screening continuum. First, only 79.5% (95% CI 75.1–83.2) of women who had a positive screening result received treatment within 2 years. This falls short of the WHO target of 90% for treatment of precancerous cervical lesions. We also found a low number of women who were screen-negative after treatment of precancerous cervical lesions (36.1%, 95% CI 31.2–40.7) which raises concerns about the effectiveness of treatment and the accuracy of screening tests used to detect precancerous cervical lesions among WLHIV.

Evidence synthesis studies
Studies 3 and 4 (Chapter 3.3 and 3.4, respectively) synthesize evidence for the management of precancerous cervical lesions and devices that may be used for colposcopy in low- and middle-income countries. Although visual assessment of the cervix remains essential for screening and treatment of precancerous cervical lesions, colposcopy is often not available in low- and middle-income countries (LMIC, Chapter 3.3). Study 4 (Chapter 3.4) is a systematic review of the diagnostic test accuracy of portable devices able to perform colposcopy. We found that when these devices are used as add-on screening tests, a pooled sensitivity of 0.79 (95% CI 0.54–0.92) and specificity of 0.83 (95% CI 0.59–0.94) is achieved. The wide confidence intervals of these estimates indicate that the accuracy of portable devices able to perform colposcopy for the detection of CIN 2+ remains uncertain.

Clinical test accuracy studies
Studies 5 and 6 (Chapter 3.5 and 3.6, respectively) refer to clinical investigations of the diagnostic test accuracy of the Gynocular™, a portable device that can be used for colposcopy. Study 5 (Chapter 3.5) is our protocol which outlines the aims and methods of the first study to evaluate the Gynocular™ in a population of WLHIV exclusively. In this study we are also evaluating other relevant point-of-care tests; the high-risk human papillomavirus test (HR-HPV, GeneXpert™, Cepheid, USA) and VIA. We plan to measure the sensitivity and specificity of each test in a stand-alone capacity as well as the combination of tests. Extensions to this study include a cost analysis, the development of an automated visual assessment tool using pattern recognition, as well as exploring associations with trichomoniasis (a common STI in this setting. Study 6 (Chapter 3.6) is a cross-sectional pilot study evaluating the telemedicine capacity of the device. Here we assessed the diagnostic accuracy of the Gynocular™ used during live colposcopy versus static-image assessments using Swede score evaluation for detecting CIN 2+ lesions. We evaluated 495 images from 94 VIA-positive women. Thirteen (13.9%) had CIN 2+ on biopsy. We found that live and static image assessors had similar accuracy for detecting CIN 2+ lesions (area under curve = 0.69 versus 0.71, p = 0.63) and the Swede score could be used to optimize sensitivity or specificity.

In conclusion, the studies presented in this thesis contribute to a sparse knowledge base on secondary prevention of cervical cancer in WLHIV. The studies suggest that cervical cancer screening and treatment quality needs to be improved for WLHIV in LMIC and that reforms must be context-specific, taking into account the population characteristics and the healthcare infrastructure concerned. These gaps need to be addressed before the WHO initiative to eliminate cervical cancer at the global level can be successful.

Item Type:	Thesis (Dissertation)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
Graduate School:	Graduate School for Cellular and Biomedical Sciences (GCB)
UniBE Contributor:	Taghavi, Katayoun, Bohlius, Julia Friederike
Subjects:	600 Technology > 610 Medicine & health 300 Social sciences, sociology & anthropology > 360 Social problems & social services
Language:	English
Submitter:	Beatrice Minder Wyssmann
Date Deposited:	09 Jun 2023 09:33
Last Modified:	09 Jun 2023 10:32
Additional Information:	Doctor of Medicine and Philosophy (MD, PhD)
URI:	https://boris.unibe.ch/id/eprint/183277