Recent developments in early detection strategies and population-based screening: the perspectives of cervical cancer and COVID-19

Gilbert, Laura (2022) Recent developments in early detection strategies and population-based screening: the perspectives of cervical cancer and COVID-19. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Early detection strategies and population-based screening are important public health tools in early detection of disease and population surveillance. This work aimed to examine cervical cancer and COVID-19 with a focus on new strategies for early detection and population-based screening data; these approaches can help detect pre-cancerous lesions before they develop into cervical cancer and can help to better understand the spread of the SARS-CoV-2 virus in the general population. While cervical cancer screening is a long-standing program, requiring review of existing programs and new methodologies, the emergence of the COVID-19 requires an initial evaluation of new test methodologies. Cervical cancer data was collected through testing enrolled patient specimens and programmatic data, and COVID-19 data was collected from testing deidentified patient specimens. This dissertation is comprised of three studies (4 manuscripts). The first study reviewed the Newfoundland and Labrador (NL) cervical screening program to assess positivity and clinical disease endpoint and reviewed programmatic indicators to determine the ability of the program to detect pre-cancerous lesions. The second study evaluated the diagnostic indices and properties of CINtec PLUS and cobas HPV tests among those referred to colposcopy with a history of low-grade squamous intraepithelial lesions (LSIL) to identify those at increased risk of pre-cancerous lesions and cervical cancer and potentially reduce the proportion requiring further followup in all age groups, for those <30 years of age, and those > 30 years of age. Finally, the third study evaluated three (2 different IgG and 1 IgA) serological tests’ abilities to detect prior infection with SARS-CoV-2 from laboratory-confirmed COVID-19. The findings indicate in the first study that while there have been attempts to improve cervical screening participation, high rates of abnormalities, pre-cancerous lesions, and invasive cancers are troubling. In the second study, high sensitivity (93.2%) and negative predictive value (NPV, 98.1% for CINtec PLUS, 97.0% for cobas) were observed in patients referred to colposcopy with a history of LSIL cytology for CINtec PLUS cytology and the cobas HPV test (CIN3+). However, the reduced sensitivity of CINtec PLUS for detection of CIN2+ in general (81.8% for CINtec PLUS, 93.9% for cobas), and CIN 2, especially in patients <30 years, needs to be considered in risk assessments if choosing LSIL-CINtec PLUS triage. Nevertheless, CINtec PLUS was consistently more specific than the HPV test. In the third study, observed sensitivities ranged from 91.3-100.0% and specificities of 90.8-98.2%; cross-reactivity was observed in the IgA test. A two-tiered approach was observed to improve performance in low prevalence settings. In conclusion, based on the review of local cervical screening programs, there are opportunities for improvement. Either test examined could serve as a predictor of CIN3+ with high sensitivity in patients referred to colposcopy with a history of LSIL regardless of age while significantly reducing the number of LSIL referral patients requiring further investigations and follow-up in colposcopy clinics. For COVID-19, IgG tests may serve as practical tools in helping detect past SARS-CoV-2 infection.

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