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      Self-sampling for human papillomavirus (HPV) testing: a systematic review and meta-analysis

      systematic-review

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          Abstract

          Introduction

          Human papillomavirus (HPV) self-sampling test kits may increase screening for and early detection of cervical cancer and reduce its burden globally. To inform WHO self-care guidelines, we conducted a systematic review and meta-analysis of HPV self-sampling among adult women on cervical (pre-)cancer screening uptake, screening frequency, social harms/adverse events and linkage to clinical assessment/treatment.

          Methods

          The included studies compared women using cervical cancer screening services with HPV self-sampling with women using standard of care, measured at least one outcome, and were published in a peer-reviewed journal. We searched PubMed, the Cumulative Index to Nursing and Allied Health Literature (CNIAHL), Latin American and Caribbean Health Sciences Literature (LILACS) and Embase through October 2018. Risk of bias was assessed using the Cochrane tool for randomised controlled trials (RCTs) and the Evidence Project tool for non-randomised studies. Meta-analysis was conducted using random-effects models to generate pooled estimates of relative risk (RR).

          Results

          33 studies in 34 articles with 369 017 total participants met the inclusion criteria: 29 RCTs and 4 observational studies. All studies examined HPV self-sampling; comparison groups were standard of care (eg, Pap smear, visual inspection with acetic acid, clinician-collected HPV testing). 93% of participants were from high-income countries. All 33 studies measured cervical cancer screening uptake. Meta-analysis found greater screening uptake among HPV self-sampling participants compared with control (RR: 2.13, 95% CI 1.89 to 2.40). Effect size varied by HPV test kit dissemination method, whether mailed directly to home (RR: 2.27, 95% CI 1.89 to 2.71), offered door-to-door (RR: 2.37, 95% CI 1.12 to 5.03) or requested on demand (RR: 1.28, 95% CI 0.90 to 1.82). Meta-analysis showed no statistically significant difference in linkage to clinical assessment/treatment between arms (RR: 1.12, 95% CI 0.80 to 1.57). No studies measured screening frequency or social harms/adverse events.

          Conclusion

          A growing evidence base, mainly from high-income countries and with significant heterogeneity, suggests HPV self-sampling can increase cervical cancer screening uptake compared with standard of care, with a marginal effect on linkage to clinical assessment/treatment.

          Systematic review registration number

          PROSPERO CRD42018114871.

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          Most cited references42

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          Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer.

          More than ever, clinicians need regularly updated reviews given the continuously increasing amount of new information regarding innovative cervical cancer prevention methods. A summary is given from recent meta-analyses and systematic reviews on 3 possible clinical applications of human papillomavirus (HPV) testing: triage of women with equivocal or low-grade cytologic abnormalities; prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN) lesions, and last not but not least, primary screening for cervical cancer and pre-cancer. Consistent evidence is available indicating that HPV-triage with the Hybrid Capture(®) 2 assay (Qiagen Gaithersburg, Inc., MD, USA [previously Digene Corp.] (HC2) is more accurate (higher sensitivity, similar specificity) than repeat cytology to triage women with equivocal Pap smear results. Several other tests show at least similar accuracy but mRNA testing with the APTIMA(®) (Gen-Probe Inc., San Diego, CA, USA) test is similarly sensitive but more specific compared to HC2. In triage of low-grade squamous intraepithelial lesions (LSIL), HC2 is more sensitive but its specificity is substantially lower compared to repeat cytology. The APTIMA(®) test is more specific than HC2 without showing a loss in sensitivity. Identification of DNA of HPV types 16 and/or 18, or RNA from the five most carcinogenic HPV types allow selecting women at highest risk for CIN3+ but the sensitivity and negative predictive value of these markers are lower than full-range high-risk HPV (hrHPV) testing. After conservative treatment of cervical pre-cancer, HPV testing picks up more quickly, with higher sensitivity and not lower specificity, residual or recurrent high-grade CIN than follow-up cytology. Primary screening for hrHPV generally detects more CIN2, CIN3 or cancer compared to cytology at cut-off atypical squamous cells of undetermined significance (ASC-US) or LSIL, but is less specific. Combined HPV and cytology screening provides a further small gain in sensitivity at the expense of a considerable loss in specificity if positive by either test is referred to colposcopy, in comparison with HPV testing only. Randomised trials and follow-up of cohort studies consistently demonstrate a significantly lower cumulative incidence of CIN3+ and even of cancer, in women aged 30 years or older, who were at enrollment hrHPV DNA negative compared to those who were cytologically negative. The difference in cumulative risk of CIN3+ or cancer for double negative (cytology & HPV) versus only HPV-negative women is small. HC2, GP5+/6+ PCR (polymerase chain reaction), cobas(®) 4800 PCR (Roche Molecular Systems Inc., Alameda, CA, USA) and Real Time PCR (Abbott Molecular, Des Plaines, IL, USA) can be considered as clinically validated for use in primary screening. The loss in specificity associated with primary HPV-based screening can be compensated by appropriate algorithms involving reflex cytology and/or HPV genotyping for HPV16 or 18. There exists a substantial evidence base to support that HPV testing is advantageous both in triage of women with equivocal abnormal cytology, in surveillance after treatment of CIN lesions and in primary screening of women aged 30 years or older. However, the possible advantages offered by HPV-based screening require a well organised program with good compliance with screening and triage policies. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2012 Marc Arbyn. Published by Elsevier Ltd.. All rights reserved.
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            HIV-positive women have higher risk of human papilloma virus infection, precancerous lesions, and cervical cancer.

            HIV-positive women have higher human papillomavirus (HPV) prevalence and cervical cancer incidence than HIV-negative women, partly because of HIV's modifying effect on HPV pathogenesis. We synthesized the literature on the impact of HIV on HPV natural history.
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              Is Open Access

              HPV testing on self collected cervicovaginal lavage specimens as screening method for women who do not attend cervical screening: cohort study

              Objective To determine whether offering self sampling of cervicovaginal material for high risk human papillomavirus (HPV) testing is an effective screening method for women who do not attend regular cervical screening programmes. Design Cohort study (the PROHTECT trial). Settings Noord-Holland and Flevoland regions of the Netherlands, December 2006 to December 2007, including 13 laboratories, gynaecologists, and more than 800 general practitioners. Participants 28 073 women who had not responded to two invitations to the regular cervical screening programme: 27 792 women were assigned to the self sampling group and invited to submit a self collected cervicovaginal sample for HPV testing; 281 were assigned to the recall control group and received a second re-invitation for conventional cytology. Intervention Women with a positive result on the high risk HPV test on their self sample material were referred to their general practitioner. Women with abnormal results on cytology were referred for colposcopy. Women with normal results on cytology were re-evaluated after one year by cytology and high risk HPV testing and referred for colposcopy if either result was positive. Main outcome measures Attendance rate in both groups and yield of cervical intraepithelial neoplasia grade II/III or worse (≥CIN II/≥CIN III) in self sampling responders. Results The compliance rate in the self sampling group was significantly higher than in the control group (crude 26.6% v 16.4%, P<0.001; adjusted 27.5% v 16.6%, P<0.001). The number of detected ≥CIN II and ≥CIN III lesions in self sampling responders was 99 (1.3%) and 76 (1.0%), respectively. Self sampling responders who had not participated in the previous round of screening (43%) had increased relative risks of ≥CIN II (2.04, 95% confidence interval 1.27 to 3.28) and ≥CIN III (2.28, 1.31 to 3.96) compared with self sampling women who had been screened in the previous round (57%). Conclusions Offering self sampling by sending a device for collecting cervicovaginal specimens for high risk HPV testing to women who did not attend regular screening is a feasible and effective method of increasing coverage in a screening programme. The response rate and the yield of high grade lesions support implementation of this method for such women. Trial registration ISRCTN45527158.
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                Author and article information

                Journal
                BMJ Glob Health
                BMJ Glob Health
                bmjgh
                bmjgh
                BMJ Global Health
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2059-7908
                2019
                14 May 2019
                : 4
                : 3
                : e001351
                Affiliations
                [1 ] departmentDepartment of International Health , Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland, USA
                [2 ] departmentInfections and Cancer Epidemiology Group , International Agency for Research on Cancer , Lyon, France
                [3 ] departmentDepartment of Reproductive Health and Research , Organisation mondiale de la Santé , Geneve, Switzerland
                Author notes
                [Correspondence to ] Dr Manjulaa Narasimhan; narasimhanm@ 123456who.int
                Author information
                http://orcid.org/0000-0002-7425-0382
                Article
                bmjgh-2018-001351
                10.1136/bmjgh-2018-001351
                6529022
                31179035
                44adf218-bc73-4ac9-ba35-21d091418c41
                © World Health Organization 2019. Licensee BMJ.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution IGO License ( https://creativecommons.org/licenses/by-nc/3.0/igo/), which permits use, distribution, and reproduction for non-commercial purposes in any medium, provided the original work is properly cited.

                History
                : 06 December 2018
                : 26 April 2019
                : 27 April 2019
                Funding
                Funded by: UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme;
                Categories
                Research
                1506
                Custom metadata
                unlocked

                human papillomavirus,cervical cancer screening,self-sampling,systematic review,meta-analysis

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