Laurie W. Smith

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens—Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral

Abstract The Netherlands’ cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037

Women’s acceptability of and experience with primary human papillomavirus testing for cervix screening: HPV FOCAL trial cross-sectional online survey results

Objective To study participant’s acceptability of and attitudes towards human papillomavirus (HPV) testing compared with cytology for cervical cancer screening and what impact having an HPV positive result may have in future acceptability of screening. Design Cross-sectional online survey of clinical trial participants. Setting Primary care, population-based Cervix Screening Program, British Columbia, Canada. Participants A total of 5532 participants from the HPV FOCAL trial, in which women received HPV and cytology testing at study exit, were included in the analysis. Median age was 54 years. The median time of survey completion was 3 years after trial exit. Outcome measures Acceptability of HPV testing for primary cervical cancer screening (primary); attitudes and patient perceptions towards HPV testing and receipt of HPV positive screen results (secondary). Results Most respondents (63%) were accepting of HPV testing, with the majority (69%) accepting screening to begin at age 30 years with HPV testing. Only half of participants (54%) were accepting of an extended screening interval of 4–5 years. In multivariable logistic regression, women who received an HPV positive screen test result during the trial (OR=1.41 95% CI 1.11 to 1.80) or were older (OR=1.01, 95% CI 1.00 to 1.02) were more likely to report HPV testing as acceptable. Conclusions In this evaluation of acceptability and attitudes regarding HPV testing for cervix screening, most are accepting of HPV testing for screening; however, findings indicate heterogeneity in concerns and experiences surrounding HPV testing and receipt of HPV positive results. These findings provide insights for the development of education, information and communication strategies during implementation of HPV-based cervical cancer screening. Trial registration numbers ISRCTN79347302 and NCT00461760.

Cost‐effectiveness analysis of primary human papillomavirus testing in cervical cancer screening: Results from the HPV FOCAL Trial

AbstractThe Human Papillomavirus FOr CervicAL cancer (HPV FOCAL) trial is a large randomized controlled trial comparing the efficacy of primary HPV testing to cytology among women in the population‐based Cervix Screening Program in British Columbia, Canada. We conducted a cost‐effectiveness analysis based on the HPV FOCAL trial to estimate the incremental cost per detected high‐grade cervical intraepithelial neoplasia of grade 2 or worse lesions (CIN2+). A total of 19,009 women aged 25 to 65 were randomized to one of two study groups. Women in the intervention group received primary HPV testing with reflex liquid‐based cytology (LBC) upon a positive finding with a screening interval of 48 months. Women in the control group received primary LBC testing, and those negative returned at 24 months for LBC and again at 48 months for exit screening. Both groups received HPV and LBC co‐testing at the 48‐month exit. Incremental costs during the course of the trial were comparable between the intervention and control groups. The intervention group had lower overall costs and detected a larger number of CIN2+ lesions, resulting in a lower mean cost per CIN2+ detected ($7551) than the control group ($8325), a difference of ‐$773 [all costs in 2018 USD]. Cost per detected lesion was sensitive to the costs of sample collection, HPV testing, and LBC testing. The HPV FOCAL Trial results suggest that primary HPV testing every 4 years produces similar outcomes to LBC‐based testing every 2 years for cervical cancer screening at a lower cost.

The social and economic impacts of cervical cancer on women and children in low‐ and middle‐income countries: A systematic review

AbstractBackgroundThere is limited knowledge on the social and economic impacts of a diagnosis of cervical cancer on women and children in low‐ and middle‐income countries (LMICs).ObjectivesTo determine the social and economic impacts associated with cervical cancer among women and children living in LMICs.Search strategyThe MEDLINE, PsychInfo, CINAHL, Pais International, and CAB Global Health databases were systematically searched to retrieve studies up to June 2021.Selection criteriaStudies were included if they reported on either the social or economic impacts of women or children in a LMIC.Data collection and analysisData was independently extracted by two co‐authors. The authors performed a quality assessment on all included articles.Main resultsIn all, 53 studies were included in the final review. Social impacts identified included social support, education, and independence. Economic impacts included employment and financial security. No study reported the economic impact on children. Studies that utilized quantitative methods typically reported more positive results than those that utilized qualitative methods.ConclusionsAdditional mixed‐methods research is needed to further understand the social support needs of women with cervical cancer. Furthermore, research is needed on the impact of a mother's diagnosis of cervical cancer on her children.

Evidence of Decreased Long-term Risk of Cervical Precancer after Negative Primary HPV Screens Compared with Negative Cytology Screens in a Longitudinal Cohort Study

Abstract Background: The growing use of primary human papillomavirus (HPV) cervical cancer screening requires determining appropriate screening intervals to avoid overtreatment of transient disease. This study examined the long-term risk of cervical precancer after HPV screening to inform screening interval recommendations. Methods: This longitudinal cohort study (British Columbia, Canada, 2008 to 2022) recruited women and individuals with a cervix who received 1 to 2 negative HPV screens (HPV1 cohort, N = 5,546; HPV2 cohort, N = 6,624) during a randomized trial and women and individuals with a cervix with 1 to 2 normal cytology results (BCS1 cohort, N = 782,297; BCS2 cohort, N = 673,778) extracted from the provincial screening registry. All participants were followed through the registry for 14 years. Long-term risk of cervical precancer or worse [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)] was compared between HPV and cytology cohorts. Results: Cumulative risks of CIN2+ were 3.2/1,000 [95% confidence interval (CI), 1.6–4.7] in HPV1 and 2.7/1,000 (95% CI, 1.2–4.2) in HPV2 after 8 years. This was comparable with the risk in the cytology cohorts after 3 years [BCS1: 3.3/1,000 (95% CI, 3.1–3.4); BCS2: 2.5/1,000 (95% CI, 2.4–2.6)]. The cumulative risk of CIN2+ after 10 years was low in the HPV cohorts [HPV1: 4.7/1,000 (95% CI, 2.6–6.7); HPV2: 3.9 (95% CI, 1.1–6.6)]. Conclusions: Risk of CIN2+ 8 years after a negative screen in the HPV cohorts was comparable with risk after 3 years in the cytology cohorts (the benchmark for acceptable risk). Impact: These findings suggest that primary HPV screening intervals could be extended beyond the current 5-year recommendation, potentially reducing barriers to screening.

HPV Testing for Cervical Cancer Screening Study

This is a randomised controlled trial of HPV testing with cytology triage for HPV positive women compared to liquid-based cervical cytology (LBC). Although LBC is not widely used for cervical cancer screening in Canada at present, the Pan-Canadian Cervical Cancer Forum has recommended its use and as it is likely to be the standard of care by the time these data are published, the trial has been designed to account for this. Further, LBC will improve the cost-effectiveness of HPV testing because the LBC medium is suitable for both HPV testing as well as cytology and thereby allows the triage testing to be undertaken from the same sample without having to recall the women.