Gina S. Ogilvie

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

Investigating the healthcare‐seeking behaviors of mobile phone users to improve cervical cancer screening in rural Uganda

Abstract Objective Cervical cancer is the leading cause of cancer in low‐ and middle‐income countries, despite being preventable. Uganda, which lacks an effective screening program, has one of the highest global cervical cancer incidence rates. Mobile health (mHealth) technology has the potential to improve healthcare‐seeking behaviors and access. The present study describes the connection between mobile phone access and healthcare‐seeking behaviors in rural Uganda. Methods Women were eligible for this cross‐sectional study if they had no prior screening or treatment for cervical cancer in the past 5 years, were aged 30 to 49 years old, and were residents of the South Busoga Forest reserve. Survey data was analyzed using descriptive statistics and chi‐square tests. Results Of the 1434 participants included in the analysis, 91.4% reported having access to a mobile phone. Most respondents were aged 30–40 years, had a partner, had ≤primary education, and were farmers. Participants with mobile phone access were significantly more likely to report attending a healthcare outreach visit (access = 87.3%, no access = 72.6%, P  < 0.001) or visiting a health center (access = 96.9%, no access = 93.5%, P  < 0.001). Participants in both groups had largely positive attitudes around and good knowledge of cervical cancer screening. Conclusion While attendance to healthcare services was high amongst participants, those with mobile phone access were more likely to seek healthcare services. Further inquiry into this association between mobile phone access and healthcare‐seeking behavior is needed to optimize the improvements to cervical cancer screening when implementing interventions such as mHealth technology.

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.

Declining rates of cervical intraepithelial neoplasia in British Columbia, Canada: An ecological analysis on the effects of the school‐based human papillomavirus vaccination program

AbstractSince 2008, girls in British Columbia (BC), Canada, have been offered HPV vaccination through a school‐based, publicly funded immunization program. The oldest birth cohort eligible for the vaccination program was born in 1994 and uptake is on average 63%. To evaluate the impact of the HPV vaccine in BC, ecological trends in cervical intraepithelial neoplasia (CIN) rates were assessed in young women before and after the implementation of the HPV vaccination program. Information on all Pap smears and histopathological abnormalities, in calendar years 2004‐2017 in women 16‐28 years of age in BC were obtained from the population‐based BC Cancer Cervix Screening Program database. Rates of CIN 2 and 3 were calculated as the number of cases divided by the number of cytology specimens for that period. Rate ratios (RR) were calculated by negative binomial piecewise regression. Age‐centered incidence rates of CIN 2 and 3 in BC declined significantly among women 16‐23 years of age after HPV vaccine introduction compared to before vaccine introduction. The overall reduction postvaccination for CIN2 and 3 in women 16‐23 years was respectively 62% (95% CI 54‐68%) and 65% (95% CI 58‐71%). Age‐specific rates for CIN2 significantly declined for those 18‐22 years of age and for those 19, 20 and 23 years of age for CIN3. Among women 24‐28 years of age no decline in CIN2 and 3 rate over time was observed. The observed reduction in CIN 2 and 3 rates since the introduction of the school‐based HPV vaccine program might illustrate the population impact of the BC provincial school‐based HPV vaccination program.

Experiences with thermal ablation for cervical precancer treatment after self‐collection HPV‐based screening in the ASPIRE Mayuge randomized trial

AbstractCervical cancer remains a significant public health burden in low‐resourced countries. Thus, the WHO prioritized cervix screening, and recently recommended thermal ablation treatment for cervical precancer. However, there is limited information on side effects during treatment and recovery, and acceptability among those treated. The ASPIRE Mayuge trial recruited women to participate in self‐collection cervix screening between 2019 and 2020 (N = 2019). Screen‐positive women (N = 531, 26.3%) were referred for visual inspection with acetic acid and thermal ablation treatment, per Uganda Ministry of Health recommendations; 71.2% of those referred attended follow‐up. Six months post‐screening, a subset of trial participants were recontacted. Those who received thermal ablation completed a survey assessing side effects during and after the procedure, and willingness to recommend the treatment to others. We summarized the results to describe the side effects and acceptability of thermal ablation treatment. Of 2019 participants, 349 (17%) received thermal ablation. A subset of 135 completed the follow‐up survey, where 90% reported pain during treatment; however, intensity and duration were low. Over a third of women reported problems with recovery for reasons including pain, discharge and bleeding. Regardless, 98% reported they would recommend the treatment to others. The use of thermal ablation to treat cervical precancer appears to be highly acceptable in this population. While many women reported side effects during the procedure and recovery, the majority said they would recommend the treatment to others. However, given the substantial proportion who reported problems with recovery, efforts should be made to provide additional resources to women after receiving thermal ablation treatment for cervical precancer.

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.

Human papillomavirus‐based screening at extended intervals missed fewer cervical precancers than cytology in the HPV For Cervical Cancer (HPV FOCAL) trial

AbstractWhile cervix screening using cytology is recommended at 2‐ to 3‐year intervals, given the increased sensitivity of human papillomavirus (HPV)‐based screening to detect precancer, HPV‐based screening is recommended every 4‐ to 5‐years. As organized cervix screening programs transition from cytology to HPV‐based screening with extended intervals, there is some concern that cancers will be missed between screens. Participants in HPV FOr CervicAL Cancer (HPV FOCAL) trial received cytology (Cytology Arm) at 24‐month intervals or HPV‐based screening (HPV Arm) at 48‐month intervals; both arms received co‐testing (cytology and HPV testing) at exit. We investigated the results of the co‐test to identify participants with cervical intraepithelial neoplasia grade 2 or higher (CIN2+) who would not have had their precancer detected if they had only their arm's respective primary screen. In the Cytology Arm, 25/62 (40.3%) identified CIN2+s were missed by primary screen (ie, normal cytology/positive HPV test) and all 25 had normal cytology at the prior 24‐month screen. In the HPV arm, three CIN2+s (3/49, 6.1%) were missed by primary screen (ie, negative HPV test/abnormal cytology). One of these three misses had low‐grade cytology findings and would also not have been referred to colposcopy outside of the trial. Multiple rounds of cytology did not detect some precancerous lesions detected with one round of HPV‐based screening. In our population, cytology missed more CIN2+, even at shorter screening intervals, than HPV‐based screening. This assuages concerns about missed detection postimplementation of an extended interval HPV‐based screening program. We recommend that policymakers consider a shift from cytology to HPV‐based cervix screening.

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.

Integrated Cervical Cancer Screening in Mayuge District Uganda (ASPIRE Mayuge)

The purpose of this pragmatic cluster randomized control trial is to test the effectiveness of cervical cancer screening follow-up completion using two implementation approaches for self-collected HPV testing in a rural, low-resource setting: 1) community health workers recruiting women door-to-door and 2) community health workers recruiting women at community health meetings. This study will also help to further understand how current patient referral systems are working between health facilities, patient and provider preferences for integrated care and health system related barriers to integrated cervical cancer screening. Hypothesis: More women will receive screening via the community health meeting but the engagement to care (i.e., visual inspection with acetic acid-our main outcome) will be greater in the door-to-door arm.

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.