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In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes. 176 464 women aged 20–64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1 214 415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma. The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40–0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46–1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25–0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15–0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 105 (1·1–12·1) and 8·7 per 105 (3·3–18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 105 (7·9–27·0) and 36·0 per 105 (23·2–53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14–0·69) than for squamous-cell carcinoma (0·78, 0·49–1·25). The rate ratio was lowest in women aged 30–34 years (0·36, 0·14–0·94). HPV-based screening provides 60–70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years. European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

Background Disparities in cervical cancer (CC) screening participation persist, with lower rates among immigrant women from low-resource countries compared to native European women. Evidence-based strategies to reach under-screened women are thus needed, such as adopting self-sampling for human papillomavirus (HPV) testing. Studies have demonstrated that women are receptive to HPV self-sampling. However, results may not be generalizable to all ethnic groups and settings. This is the first study in Spain assessing HPV self-sampling acceptability among immigrant populations. A mixed-methods study was used to explore knowledge and perceptions of CC screening and attitudes towards HPV self-sampling among Moroccan and Pakistani women in Catalonia. Methods Eight focus group discussions and twenty-two semi-structured interviews were conducted. After a short demonstration of two self-sampling devices, women were invited to try them at home and complete an acceptability survey for each device, including questions assessing screening preferences, perceived self-efficacy, trust in the test results and willingness to use the self-collection method again. Results Important barriers, such as lack of information about CC screening, and misconceptions about HPV risk were identified. Overall, Moroccan and Pakistani women expressed a preference for clinician-based screening over self-sampling. Over half of the participants (56%) accepted to try at least one self-sampling device. However, concerns about collecting the sample correctly and distrust in the test result were raised. Conclusion Increasing awareness and empowering Moroccan and Pakistani women with culturally appropriate information about the benefits of CC screening is the first step to successfully implement HPV self-sampling. Concerns regarding self-efficacy need also to be addressed before implementing new organised screening programmes using HPV self-sampling in Catalonia, Spain. A peer-based approach using culturally appropriate materials is proposed to best inform, educate, foster confidence, and advocate for the uptake of HPV self-sampling among these two groups of women.

Testing for human papillomavirus (HPV) DNA is reportedly more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial, which was done over two screening rounds approximately 3 years apart (2001–03 and 2004–07) by comparing liquid-based cytology (LBC) combined with HPV testing against LBC alone. Women aged 20–64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were randomly assigned (between July, 2001, and September, 2003) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on, or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator. The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second screening round, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821. There were 24 510 eligible women at entry (18 386 in the revealed group, 6124 in the concealed group). In the first round of screening 233 women (1·27%) in the revealed group had CIN3+, compared with 80 (1·31%) women in the concealed group (odds ratio [OR] 0·97, 95% CI 0·75–1·25; p>0·2). There was an unexpectedly large drop in the proportion of women with CIN3+ between the first and second rounds of screening in both groups, at 0·25% (29 of 11 676) in the revealed group and 0·47% (18 of 3866 women) in the concealed group (OR 0·53, 95% CI 0·30–0·96; p=0·042). For both rounds combined, the proportion of women with CIN3+ were 1·51% (revealed) and 1·77% (concealed) (OR 0·85, 95% CI 0·67–1·08; p>0·2). LBC combined with HPV testing resulted in a significantly lower detection rate of CIN3+ in the second round of screening compared with LBC screening alone, but the effect was small. Over the two screening rounds combined, co-testing did not detect a higher rate of CIN3+ or CIN2+ than LBC alone. Potential changes in screening methodology should be assessed over at least two screening rounds. National Institute of Health Research Health Technology Assessment Programme.

Cervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen-triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa. WLHIV aged 25-50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol's iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%-52.7%) and CIN3+ (56.1%, 95% CI 43.3%-68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%-81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%-93.2%) for CIN2+ and 86.4% (95% CI 75.7%-93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%-58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%-76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%-86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28-2.32; CIN3+: 1.18, 95% CI 0.94-1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%-77.9%; CIN3+: 80.8%, 95% CI 67.5%-90.4%) and specificity (81.6%, 95% CI 77.6%-85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%-91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%-47.1%; relative specificity = 0.57, 95% CI 0.52-0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%-3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%-3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%-1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today. In this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso. The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol's iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019). The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31-41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0. Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases.

Recent reports suggest that the reduction in mortality achieved by the UK national cervical screening programme is too small to justify its financial and psychosocial costs, except perhaps in a few high-risk women. We analysed trends in mortality before 1988, when the British national screening programme was launched, to estimate what future trends in cervical cancer mortality would have been without any screening. Cervical cancer mortality in England and Wales in women younger than 35 years rose three-fold from 1967 to 1987. By 1988, incidence in this age-range was among the highest in the world despite substantial opportunistic screening. Since national screening was started in 1988, this rising trend has been reversed. Cervical screening has prevented an epidemic that would have killed about one in 65 of all British women born since 1950 and culminated in about 6000 deaths per year in this country. However, these estimates are subject to substantial uncertainty, particularly in relation to the effects of oral contraceptives and changes in sexual behaviour. 80% or more of these deaths (up to 5000 deaths per year) are likely to be prevented by screening, which means that about 100000 (one in 80) of the 8 million British women born between 1951 and 1970 will be saved from premature death by the cervical screening programme at a cost per life saved of about £36 000. The birth cohort trends also provide strong evidence that the death rate throughout life is substantially lower in women who were first screened when they were younger.

To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA). Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later. Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77-10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11-20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14-12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23-8.54). HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37-90% of CIN2+ among African WLHIV.

BackgroundLong-term follow-up of large cohorts is needed to determine the effects of HPV and screening on CIN3 (grade 3 cervical intraepithelial neoplasia) and ICC (invasive cervical cancer).MethodsWomen were recruited when attending for routine cervical screening in Greater Manchester, UK: 1987–93 for the Manchester Cohort (MC: 47,625 women) and 2001–03 for the ARTISTIC Cohort (AC: 24,496 women). Both were followed through national registration for cancer incidence and mortality to 2020.ResultsRisk patterns following HPV infection differed for CIN3 and ICC. Risk of ICC in the MC rises for 30 years following a single positive HPV test, reaching 2.5% (95% CI: 1.3–4.5%). A similar pattern was seen in the AC, but the risks of cancer were approximately halved. CIN3 was diagnosed much sooner in the AC due to more efficient cytology. More sensitive HPV testing was able to better predict future risk.ConclusionThe sensitivity of HPV testing and cytology influences the CIN3 detection rate. Sensitive HPV testing enables effective risk stratification. Increased risk of ICC is observed 15–30 years after HPV infection. Women testing HPV + should be followed until their infection clears. Discharging women from screening programmes whilst they remain HPV + may not be safe, even if cytology and colposcopy tests are normal.

BackgroundWe have conducted a population-based study of pleural mesothelioma patients with occupational histories and measured asbestos lung burdens in occupationally exposed workers and in the general population. The relationship between lung burden and risk, particularly at environmental exposure levels, will enable future mesothelioma rates in people born after 1965 who never installed asbestos to be predicted from their asbestos lung burdens.MethodsFollowing personal interview asbestos fibres longer than 5 µm were counted by transmission electron microscopy in lung samples obtained from 133 patients with mesothelioma and 262 patients with lung cancer. ORs for mesothelioma were converted to lifetime risks.ResultsLifetime mesothelioma risk is approximately 0.02% per 1000 amphibole fibres per gram of dry lung tissue over a more than 100-fold range, from 1 to 4 in the most heavily exposed building workers to less than 1 in 500 in most of the population. The asbestos fibres counted were amosite (75%), crocidolite (18%), other amphiboles (5%) and chrysotile (2%).ConclusionsThe approximate linearity of the dose–response together with lung burden measurements in younger people will provide reasonably reliable predictions of future mesothelioma rates in those born since 1965 whose risks cannot yet be seen in national rates. Burdens in those born more recently will indicate the continuing occupational and environmental hazards under current asbestos control regulations. Our results confirm the major contribution of amosite to UK mesothelioma incidence and the substantial contribution of non-occupational exposure, particularly in women.

Pooled results of four randomised controlled trials in Europe showed that HPV testing reduces cervical cancer risk. 1 The British ARTISTIC trial 2 and several other studies have also shown that it gives longer protection for cervical intraepithelial neoplasia grade 3 (CIN3). The primary aim of cervical screening is to prevent cancer, and the 22 cancers observed among HPV negative women in this very large study, suggesting an invasive cancer risk of the order of 1 in 1000 after a 10-year screening interval, are a major addition to the evidence. Collaborative pooling of data and modelling studies are needed to estimate the effects on early and advanced cancer incidence of HPV testing with screening intervals of up to 10 years at different ages, and particularly at a woman's final HPV test.