Exposure Definition in Case-Control Studies of Cervical Cancer Screening: A Systematic Literature Review.

The first step in evaluating the effectiveness of cervical screening is defining exposure to screening. Our aim was to describe the spectrum of screening exposure definitions used in studies of the effectiveness of cervical screening. This systematic review included case-control studies in a population-based screening setting. Outcome was incidence of cervical cancer. Three electronic databases were searched from January 1, 2012 to December 6, 2018. Articles prior to 2012 were identified from a previous review. The qualitative synthesis focused on describing screening exposure definitions reported in the literature and the methodologic differences that could have an impact on the association between screening and cervical cancer. Forty-one case-control studies were included. Six screening exposure definitions were identified. Cervical cancer risk on average decreased by 66% when screening exposure was defined as ever tested, by 77% by time since last negative test, and by 79% after two or more previous tests. Methodologic differences included composition of the reference group and whether diagnostic and/or symptomatic tests were excluded from the analysis. Consensus guidelines to standardize exposure definitions are needed to ensure evaluations of cervical cancer screening can accurately measure the impact of transitioning from cytology to human papillomavirus-based screening and to allow comparisons between programs.

Will COVID-19 Be the Tipping Point for Primary HPV Self-sampling?

Self-sampling is poised to be a disruptor for cervical screening. So far, cancer screening has been a causality of COVID-19; however, the opposite may transpire for self-sampling. Self-sampling enables socially distanced cervical screening with an outreach that extends to underserved populations. As evidence mounts that self-sampling is noninferior to clinician-taken samples, the focus for self-sampling is now as a primary screening option for all women. Now, we have evidence from a modeling study (using Australia as an exemplar) to suggest that program effectiveness with primary self-sampling would be better than the current program, even if sensitivity is lower. Regulatory issues, suitable triage strategies, and clear communication about self-sampling are hurdles yet to be overcome. Nevertheless, existing evidence coupled with COVID-19 could be the tipping point for wider introduction of self-sampling.See related article by Smith et al., p. 268.

Measuring the nature and duration of symptoms of cervical cancer in young women: developing an interview-based approach.

BACKGROUND: Some young women experience delays in diagnosis of cervical cancer, but little research about ways of studying these delays has been published. A major challenge is that gynaecological symptoms are common in young women, but cervical cancer is rare. This study describes the development and testing of a measure for studying delays in diagnosis in young women with cervical cancer. METHODS: Prospective development of an interview measure and testing of its ability to reliably and systematically collect relevant data in two large hospitals in London, UK using 27 women aged 18-40 diagnosed with cervical cancer in the previous two years. We developed a semi-structured interview schedule and data extraction form to systematically collect data on symptoms (including nature and duration) and risk factors for delayed diagnosis from young women with cervical cancer. We piloted the measure among young women with cervical cancer (audiorecording it with their permission), refining it iteratively. To complete the measure, we developed a database for managing the data and a manual for using the schedule. Two researchers extracted data from the recorded interviews to assess inter-rater reliability. RESULTS: The final interview schedule yielded quantitative data on the nature and duration of symptoms and risk factors for delayed diagnosis. Inter-rater reliability was high. In the pilot, 12 of the 27 women were diagnosed via symptomatic presentation. Median time from the symptom triggering presentation to presentation was one month (interquartile range 0-4 months). Median time from presentation to diagnosis was three months (interquartile range 1-8.5 months). CONCLUSIONS: We have developed a reliable tool for measuring the nature and duration of symptoms in young women with cervical cancer. Pilot data suggest that a substantial proportion of women experience delay between first presentation and diagnosis.

Predictive value of symptoms for ovarian cancer: comparison of symptoms reported by questionnaire, interview, and general practitioner notes.

BACKGROUND: Because of the poor survival outcomes associated with advanced ovarian cancer, early detection strategies are needed. Although several symptom indices have been described, their relationship with the potential lead time has been poorly documented. METHODS: Women aged 50-79 years who had newly diagnosed ovarian cancer (n = 194) and control subjects (n = 268) who attended ovarian cancer screening clinics were included in the analysis. Symptoms and their onset dates were obtained from three sources: a questionnaire (191 case patients and 268 control subjects), telephone interview (111 case patients and 125 control subjects), and general practitioner (GP) notes (171 case patients and 227 control subjects). Data from questionnaires and GP notes were used to derive two new symptom indices (Index 1 and Index 2). Sensitivity and specificity for these new indices and the previously reported Goff index were calculated for the periods of 0-11 and 3-14 months before diagnosis for all three data sources. RESULTS: For each data source and period, the two new symptom indices derived from questionnaire and GP notes were similar both qualitatively (symptoms included) and quantitatively (sensitivity and specificity) to the Goff index. When symptoms that started within 3 months before diagnosis were excluded, sensitivity was decreased for all indices and all data sources (eg, for telephone interviews, sensitivity for the period 0-11 vs 3-14 months before diagnosis: for Index 1 = 91.0% vs 69.4%, difference = 21.6%, 95% confidence interval [CI] = 13.6% to 29.7%; for Index 2 = 91.0% vs 60.4%, difference = 30.6%, 95% CI = 21.7% to 39.6%; and for the Goff index = 75.7% vs 51.4%, difference = 24.3%, 95% CI = 16.0% to 32.7%). Also, the specificity of all indices was consistently decreased for telephone interviews compared with questionnaires and GP notes (eg, 1 - specificity for the period of 3-14 months before diagnosis for telephone interviews vs questionnaires: for Index 1 = 19.2% vs 10.4%, difference = 8.8%, 95% CI = 1.0% to 16.6%; for Index 2 = 14.4% vs 6.7%, difference = 7.7%, 95% CI = 0.9% to 14.5%; and for the Goff Index = 7.2% vs 1.5%, difference = 5.7%, 95% CI = 0.9% to 10.5%). CONCLUSIONS: Previous estimates of index performance have been overly optimistic because they did not take into account the time required to make a diagnosis on the basis of testing in response to symptoms. In addition, the specificity of a symptom index is lower when based on a telephone interview vs questionnaire or GP notes. Thus, the clinical utility of a symptom index depends on precisely how it is used and how index-positive women are managed.