Cervical cancer screening coverage remains insufficient in most countries. Our objective was to assess whether in-home vaginal self-sampling with a dry swab for high-risk human papillomavirus ...(HR-HPV) testing is effective and cost-effective in increasing participation in cervical cancer screening.
In March 2012, 6000 unscreened women aged 30-65 years, living in a French region covered by a screening programme, who had not responded to an initial invitation to have a Pap smear were equally randomised to three groups: 'no intervention'; 'recall', women received a letter to have a Pap smear; and 'self-sampling', women received a self-sampling kit to return to a centralised virology laboratory for PCR-based HPV testing.
Participation was higher in the 'self-sampling' than in the 'no intervention' group (22.5% vs 9.9%, P<0.0001; OR 2.64) and 'recall' group (11.7%, P<0.0001; OR 2.20). In the 'self-sampling' group, 320 used the self-sampling kit; for 44 of these women with positive HR-HPV test results, 40 had the recommended triage Pap smear. The ICER per extra screened woman was 77.8euro and 63.2euro for the 'recall' and 'self-sampling' groups, respectively, relative to the 'no intervention' group.
Offering an in-home, return-mail kit for vaginal self-sampling with a dry swab is more effective and cost-effective than a recall letter in increasing participation in cervical cancer screening.
To evaluate the diagnostic accuracy of high-risk human papillomavirus (hrHPV) assays on self samples and the efficacy of self sampling strategies to reach underscreened women.
Updated meta-analysis.
...Medline (PubMed), Embase, and CENTRAL from 1 January 2013 to 15 April 2018 (accuracy review), and 1 January 2014 to 15 April 2018 (participation review).
Accuracy review: hrHPV assay on a vaginal self sample and a clinician sample; and verification of the presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by colposcopy and biopsy in all enrolled women or in women with positive tests. Participation review: study population included women who were irregularly or never screened; women in the self sampling arm (intervention arm) were invited to collect a self sample for hrHPV testing; women in the control arm were invited or reminded to undergo a screening test on a clinician sample; participation in both arms was documented; and a population minimum of 400 women.
56 accuracy studies and 25 participation trials were included. hrHPV assays based on polymerase chain reaction were as sensitive on self samples as on clinician samples to detect CIN2+ or CIN3+ (pooled ratio 0.99, 95% confidence interval 0.97 to 1.02). However, hrHPV assays based on signal amplification were less sensitive on self samples (pooled ratio 0.85, 95% confidence interval 0.80 to 0.89). The specificity to exclude CIN2+ was 2% or 4% lower on self samples than on clinician samples, for hrHPV assays based on polymerase chain reaction or signal amplification, respectively. Mailing self sample kits to the woman's home address generated higher response rates to have a sample taken by a clinician than invitation or reminder letters (pooled relative participation in intention-to-treat-analysis of 2.33, 95% confidence interval 1.86 to 2.91). Opt-in strategies where women had to request a self sampling kit were generally not more effective than invitation letters (relative participation of 1.22, 95% confidence interval 0.93 to 1.61). Direct offer of self sampling devices to women in communities that were underscreened generated high participation rates (>75%). Substantial interstudy heterogeneity was noted (I
>95%).
When used with hrHPV assays based on polymerase chain reaction, testing on self samples was similarly accurate as on clinician samples. Offering self sampling kits generally is more effective in reaching underscreened women than sending invitations. However, since response rates are highly variable among settings, pilots should be set up before regional or national roll out of self sampling strategies.
Secondary prevention of cervical cancer Basu, Partha; Mittal, Srabani; Bhadra Vale, Diama ...
Best practice & research. Clinical obstetrics & gynaecology,
February 2018, 2018-Feb, 2018-02-00, Letnik:
47
Journal Article
Recenzirano
Cervical cancer affects women in their reproductive ages. Screening is an important secondary prevention strategy. The long process of carcinogenic transformation from human papillomavirus (HPV) ...infection to invasive cancer provides ample opportunities to detect the disease at a stage when treatment is highly effective. Suitable screening tests are cytology, visual inspection after acetic acid application and HPV detection tests. Evidence of effectiveness of the tests to reduce cervical cancer mortality and the cost-effectiveness of screening programs have been demonstrated. Cervical intraepithelial neoplasia grade 2 and grade 3 are the high-grade cervical cancer precursors and need to be treated. Treatment is safe and effective with ablative or excisional techniques. The World Health Organization recommends screening women at least once in a lifetime between 30 and 49 years of age and ensuring effective treatment of the detected abnormalities. Combination of HPV vaccination and population-based screening will be instrumental in eliminating cervical cancer.
•Cervical cancer is a major public health problem causing large number of premature deaths particularly in the developing countries.•Systematic screening of women through population-based programs can significantly reduce cervical cancer mortality.•Developing countries bearing highest burden of the disease should pragmatically select an affordable screening strategy.•Ensuring appropriate treatment and follow-up of screen-positive women is key to the success of the screening program.
Liquid-based cytology has been developed as an alternative for conventional cervical cytology. Despite numerous studies and systematic reviews, controversy remains about its diagnostic accuracy.
To ...assess the performance of liquid-based cytology compared with conventional cytology in terms of detection of histologically confirmed cervical intraepithelial neoplasia (CIN).
Cluster randomized controlled trial involving 89,784 women aged 30 to 60 years participating in the Dutch cervical screening program at 246 family practices. One hundred twenty-two practices were assigned to use liquid-based cytology and screened 49,222 patients and 124 practices were assigned to use the conventional Papanicolaou (Pap) test and screened 40,562 patients between April 2004 and July 1, 2006. Patients were followed up for 18 months through January 31, 2008.
Screening for CIN using liquid-based cytology or conventional papanicolaou (Pap) test and the blinded review of all follow-up of screen-positive women (blinded to the type of cytology and the initial result).
Intention-to-treat and per-protocol analysis of the detection rates of and positive predictive values for histologically verified CIN in both cytology systems. Outcomes are presented as crude and adjusted rate ratios (adjustment for age, urbanization, study site, and period).
The adjusted detection rate ratios for CIN grade 1+ was 1.01 (95% confidence interval CI, 0.85-1.19); for CIN grade 2+, 1.00 (95% CI, 0.84-1.20); for CIN grade 3+, 1.05 (95% CI, 0.86-1.29); and for carcinoma, 1.69 (95% CI, 0.96-2.99). The adjusted positive predictive value (PPV) ratios, considered at several cytological cutoffs and for various outcomes of CIN did not differ significantly from unity.
This study indicates that liquid-based cytology does not perform better than conventional Pap tests in terms of relative sensitivity and PPV for detection of cervical cancer precursors.
trialregister.nl Identifier: NTR1032.
Abstract Background Screening reduces cervical cancer incidence and mortality. Objective To describe cervical cancer epidemiology and screening guidelines in six low- and middle-income countries ...(LMICs) participating in the Study on global AGEing and adult health (SAGE). Search strategy Incidence, mortality, and screening-rate data were obtained for six LMICs and three higher-income comparator countries (Australia, USA, and UK). SCOPUS and PubMed were used to identify literature published after 2000 in English, using several screening-linked terms. Selection Criteria Literature describing the use of cervical cancer screening guidelines in China, Ghana, India, Mexico, Russia, and South Africa were included. Data collection and analysis Incidence, mortality trends, and screening rates were graphed and screening recommendations were summarized. Main Results Higher rates of cervical cancer incidence, mortality, and 5-year prevalence were found in LMICs compared with the comparator countries. LMICs with absent or newly implemented screening guidelines had the lowest rates of crude and effective cervical cancer screening, with high cancer incidence and mortality. Countries with established guidelines had higher screening rates and lower disease burden. Cost, inadequate knowledge, geographical location, and cultural views were common barriers to effective screening coverage. Conclusion Work must continue to improve the implementation of affordable, relevant, and achievable methods to improve screening coverage in LMICs.
Attendance at early recall and colposcopy is crucial to attaining the benefits of primary high‐risk human papillomavirus (HR‐HPV)‐based screening. Within the English HPV pilot, we analysed ...deprivation‐ and age‐related patterns of attendance at colposcopy and 12‐ and 24‐month early recall of HR‐HPV positive women screened in 2013 to 2015 (N = 36 466). We fitted logistic regression models for adjusted odds ratios (OR). Despite high overall attendance, area deprivation had a small but significant impact at both early recalls, for example, attendance at 24 months was 86.3% and 83.0% in less vs more deprived areas, respectively (ORadj: 0.76; 95% CI: 0.67‐0.87). Older women (≥30 years) were more likely to attend early recall than younger women (<30 years), for example, attendance at 24 months was 86.1% vs 82.3%, respectively (ORadj: 1.32, 95% CI: 1.16‐1.51). Most women attended colposcopy following a baseline referral, with 96.9% attendance among more deprived and 97.8% among less deprived areas (ORadj: 0.70; 95% CI: 0.55‐0.88). Differences in colposcopy attendance by deprivation level at 12 and 24 months were of approximately the same magnitude. In conclusion, attendance at early recall and colposcopy was reassuringly high. Although there were statistically significant differences by deprivation and age group, these were small in absolute terms.
We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, ...incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% 95% confidence interval (CI), 77 to 85% were positive, including 78% of patients with early-stage disease. The sensitivity in 245 ovarian cancer patients was 33% (95% CI, 27 to 39%), including 34% of patients with early-stage disease. In contrast, only 1.4% of 714 women without cancer had positive Pap brush samples (specificity, ~99%). Next, we showed that intrauterine sampling with a Tao brush increased the detection of malignancy over endocervical sampling with a Pap brush: 93% of 123 (95% CI, 87 to 97%) patients with endometrial cancer and 45% of 51 (95% CI, 31 to 60%) patients with ovarian cancer were positive, whereas none of the samples from 125 women without cancer were positive (specificity, 100%). Finally, in 83 ovarian cancer patients in whom plasma was available, circulating tumor DNA was found in 43% of patients (95% CI, 33 to 55%). When plasma and Pap brush samples were both tested, the sensitivity for ovarian cancer increased to 63% (95% CI, 51 to 73%). These results demonstrate the potential of mutation-based diagnostics to detect gynecologic cancers at a stage when they are more likely to be curable.
The principal objective was to compare automation-assisted reading of cervical cytology with manual reading using the histological end point of cervical intraepithelial neoplasia grade II (CIN2) or ...worse (CIN2+). Secondary objectives included (i) an assessment of the slide ranking facility of the Becton Dickinson (BD) FocalPoint™ Slide Profiler (Becton Dickinson, Franklin Lakes, NJ, USA), especially 'No Further Review', (ii) a comparison of the two approved automated systems, the ThinPrep® Imaging System (Hologic, Bedford, MA, USA) and the BD FocalPoint Guided Screener Imaging System, and (iii) automated versus manual in terms of productivity and cost-effectiveness.
A 1 : 2 randomised allocation of slides to either manual reading or automation-assisted paired with manual reading. Cytoscreeners were blinded to whether samples would be read only manually or manually paired with automated. Slide reading procedures followed real-life laboratory protocol to produce a final result and, for paired readings, the worse result determined the management. Costs per event were estimated and combined with productivity to produce a cost per slide, per woman and per CIN2+ and cervical intraepithelial neoplasia grade III (CIN3) or worse (CIN3+) lesion detected. Cost-effectiveness was estimated using cost per CIN2+ detected. Lifetime cost-effectiveness in terms of life-years and quality-adjusted life-years was estimated using a mathematical model.
Liquid-based cytology samples were obtained in primary care, and a small number of abnormal samples were obtained from local colposcopy clinics, from different women, in order to enrich the proportion of abnormals. All of the samples were read in a single large service laboratory. Liquid residues used for human papillomavirus (HPV) triage were tested (with Hybrid Capture 2, Qiagen, Crawley, UK) in a specialist virology laboratory in Edinburgh, UK. Histopathology was read by a specialist gynaecological pathology team blinded to HPV results and type of reading.
Samples were obtained from women aged 25-64 years undergoing primary cervical screening in Greater Manchester, UK, with small proportions from women outside this age range and from women undergoing colposcopy.
The principal intervention was automation-assisted reading of cervical cytology slides which was paired with a manual reading of the same slide. Low-grade cytological abnormalities (borderline and mild dyskaryosis) were triaged with HPV testing to direct colposcopy referral. Women with high-grade cytology were referred for colposcopy and those with negative cytology were returned to recall.
The principal outcome measure was the sensitivity of automation-assisted reading relative to manual for the detection of CIN2+. A secondary outcome measure was cost-effectiveness of each type of reading to detect CIN2+. The study was powered to detect a relative sensitivity difference equivalent to an absolute difference of 5%.
The principal finding was that automated reading was 8% less sensitive relative to manual, 6.3% in absolute terms. 'No further review' was very reliable and, if restricted to routine screening samples, < 1% of CIN2+ would have been missed. Automated and manual were very similar in terms of cost-effectiveness despite a 60%-80% increase in productivity for automation-assisted reading.
The significantly reduced sensitivity of automated reading, combined with uncertainty over cost-effectiveness, suggests no justification at present to recommend its introduction. The reliability of 'no further review' warrants further consideration as a means of saving staff time.
Current Controlled Trials ISRCTN66377374.
This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 3. See the HTA programme website for further project information.
Within 2021, Norway intends to complete implementation of HPV DNA-based primary screening for cervical cancer for women 34-69 years, while continue cytology-based screening for women 25-33 years. ...Over the recent years, the incidence of cervical cancer has increased by 30% among women younger than 40 years. In this subset of women, nearly 30% were diagnosed with a normal smear, as most recent smear, prior the cancer diagnosis. This observation demands quality control of normal smears. The aim of this study was to assess increase in program sensitivity of CIN2+ after follow-up of women with false negative Pap-smears testing positive for a 3-type (-16, -18, -45) HPV mRNA test in a cohort design over one screening interval. 521 women, aged 23-39 years, and no prior history of CIN1+ or HSIL, with an ASC-US or worse smear (ASC-US+) and 1444 women with normal screening cytology comprised the study cohorts. The positivity rate for the 3-type HPV mRNA was 1.9% (28/1444). Rescreening revealed 23 women with ASC-US, two women with LSIL, two women with ASC-H, and one woman with AGUS. If the HPV mRNA-positivity rate and histology findings from samples rescreened were applied to all women with normal cytology, an estimated increase in screening sensitivity of 16.4% (95% CI:15.3-17.5) for CIN2+ and 17.3% (95% CI:16.2-18.4) for CIN3+ were achieved. By rescreening less than 2% of women with normal cytology positive for a 3-type HPV mRNA test, we achieved a significant increase in screening program sensitivity.
It is well established that screening can prevent cervical cancer, but the magnitude of the impact of regular screening on cervical cancer mortality is unknown.
Population-based case-control study ...using prospectively recorded cervical screening data, England 1988-2013. Case women had cervical cancer diagnosed during April 2007-March 2013 aged 25-79 years (N=11 619). Two cancer-free controls were individually age matched to each case. We used conditional logistic regression to estimate the odds ratio (OR) of developing stage-specific cancer for women regularly screened or irregularly screened compared with women not screened in the preceding 15 years. Mortality was estimated from excess deaths within 5 years of diagnosis using stage-specific 5-year relative survival from England with adjustment for age within stage based on SEER (Surveillance, Epidemiology and End Results, USA) data.
In women aged 35-64 years, regular screening is associated with a 67% (95% confidence interval (CI): 62-73%) reduction in stage 1A cancer and a 95% (95% CI: 94-97%) reduction in stage 3 or worse cervical cancer: the estimated OR comparing regular (⩽5.5yearly) screening to no (or minimal) screening are 0.18 (95% CI: 0.16-0.19) for cancer incidence and 0.08 (95% CI: 0.07-0.09) for mortality. It is estimated that in England screening currently prevents 70% (95% CI: 66-73%) of cervical cancer deaths (all ages); however, if everyone attended screening regularly, 83% (95% CI: 82-84%) could be prevented.
The association between cervical cancer screening and incidence is stronger in more advanced stage cancers, and screening is more effective at preventing death from cancer than preventing cancer itself.
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