Background
Description of condition and natural history of disease
Cytology | Histology | |||
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Dysplasia | Bethesda | BSCC | CIN | SIL |
Atypia | ASCUS | Borderline change in squamous cells | Atypia | |
Borderline change in endocervical cells | ||||
HPV effect | LSIL | Low-grade dyskaryosis | HPV effect | LSIL |
Mild dysplasia | CIN 1 | |||
Moderate dysplasia | HSIL | High-grade dyskaryosis (moderate) | CIN 2 | HSIL |
Severe dysplasia | High-grade dyskaryosis (severe) | CIN 3 | ||
Carcinoma in situ | High-grade dyskaryosis/?invasive squamous carcinoma | |||
Cancer | Cancer | ?Glandular neoplasia of endocervical type | Cancer | AIS |
?Glandular neoplasia (non-cervical) |
Burden of disease
Prophylactic HPV vaccination
Screening for cervical cancer
Rationale and scope of systematic review
Methods
Systematic review conduct
Key questions and analytical framework
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KQ 1: What are the effectiveness (benefits and harms) and comparative effectiveness of different screening strategies for the prevention and early detection of cervical cancer?
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KQ 1a: Do the effectiveness and comparative effectiveness of different screening strategies for the prevention and early detection of cervical cancer differ by age or by other population subgroups?
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KQ 2: What is the comparative accuracy of screening tests for the prevention and early detection of cervical cancer?
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KQ 2a: Does the comparative accuracy of screening tests differ by age or by HPV vaccination status?
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KQ 3: What are the adverse pregnancy outcomes associated with conservative management of CIN? (NB. will not require a new or updated systematic review)
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KQ 4: What is the relative importance individuals place on the potential outcomes from screening for the prevention and early detection of cervical cancer?
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KQ 5: What is the effectiveness of primary care-based interventions to increase rates of screening for the prevention and early detection of cervical cancer for under- and never screened individuals?
Criterion | Inclusion | Exclusion |
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Population | Individuals with a cervix, 15 years of age and older, who have been sexually active, and who have no symptoms of cervical cancera Population subgroups: – By age group (15–19, 20–24, 25–29, 30–69, 70+) – Risk groups: immunocompromised (e.g. HIV, organ transplantation, chemotherapy or chronic use of corticosteroids, use of disease-modifying anti-rheumatic drugs or biologics); risk behaviours (e.g. early sexual debut, women who have sex with women, individuals who have multiple sexual partners, smoking); under or never screened (e.g. transgender individuals, individuals with a history of trauma or abuse); Indigenous peoples; rural populations; immigrants; race or ethnicity; low socioeconomic status; pregnant individuals; HPV-vaccinated populations | Study population includes > 25% individuals with recent abnormal screening result |
Intervention | Any screening strategy using hrHPV tests and/or cytology with subsequent follow-up of abnormal tests: – Primary screening with cytology (conventional or liquid-based) – Primary screening with hrHPV testing – Cytology screening, which if abnormal may be followed by triage with an hrHPV test – hrHPV screening, which if positive may be followed by triage with cytology or other hrHPV test (e.g. full genotyping) – Other combinations will be considered | HPV test using in situ hybridization, p16 immunostaining, or HPV viral load Urine for sample collection Point-of-care tests Co-testing as a strategy (although we will include relevant data for the individual strategies where suitable) |
Comparator | Effectiveness: No routine screening Comparative effectiveness: Any screening strategy differing by one or more of the following factors: – Screening test strategy – Screening interval – Universal vs. selective/targeted (e.g. starting age) – Method of sample collection (e.g. self-collectionb (self-collection at home vs. self-collection in clinic) vs. health provider collection) – Protocol for evaluation of abnormal screening results (e.g. criteria for immediate colposcopy) | |
Outcomes | Critical outcomes: – Incidence of invasive cervical cancer (squamous and adenocarcinoma) – Incidence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3c – Cervical cancer mortality – All-cause mortality – Overdiagnosis of CIN 2 and CIN 3 and invasive cervical cancerc Important outcomes: – Number and rates of colposcopy and/or biopsy, including LEEP and other treatments provided during colposcopy (or referral rate) (for comparative effectiveness) – Adverse pregnancy outcomes from conservative, local management of CIN – False-positive rate for detecting CIN 2 and CIN 3 and invasive cancerc | |
Timing | No limitation on the duration of follow-up; results will be reported by screening round and longest follow-up | |
Setting | Studies from Very High Human Development Index countries | |
Study design | – Randomized controlled trials – If insufficient data from randomized controlled trials (by comparison and outcome): non-randomized studies (controlled trials, before-after studies, interrupted time series, individual patient data meta-analysis, cohort studies, case-control studies) | Conference proceedings; government reports; systematic reviews; case reports; editorials |
Language | English or French | |
Publication date | 1995–present |
Eligibility criteria
Criterion | Inclusion | Exclusion |
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Population | Individuals with a cervix, 15 years of age and older, who have been sexually active, and who have no symptoms of cervical cancera Population subgroups: – By age group (15–19, 20–24, 25–29, 30–69, 70+) – HPV-vaccinated populations | Study population includes > 25% individuals with recent abnormal screening results |
Index screening test | – Primary high-risk HPV testing with HPV nucleic acid testsb alone – High-risk HPV testing with HPV nucleic acid tests, followed by some form of triage (e.g. cytology or HPV testing with partial genotyping for HPV 16 or 18, sequential partial genotyping for HPV 16 or 18 followed by cytology to further triage those positive for HPV 16 or 18). Subgroups: – Method of sample collection for high-risk HPV testing (i.e. self-collected (home vs. in clinic) vs. clinician-collected) – Type of assay (i.e. generic, partial genotyping, full genotyping) – HPV test threshold for a positive result (i.e. 1 pg/mL, 2 pg/mL) | HPV test using in situ hybridization, p16 immunostaining, or HPV viral load Earlier versions of commercial tests that have been replaced (e.g. Hybrid Capture 1) Urine for sample collection Point-of-care tests |
Comparator screening test | – Conventional or liquid-based cytology, with or without follow-up by high-risk HPV testing – High-risk HPV testing with HPV nucleic acid tests, followed by different forms of triage than in the index test – hrHPV testing with HPV nucleic acid tests, using a different method of sample collection (i.e. self-sampled (home vs. clinic) vs. clinician-sampled) | Visual inspection with acetic acid or visual inspection with Lugol’s iodine |
Reference standards | • Colposcopy with histologic examination of tissue specimens, when indicated. • Study protocol stipulates that reference standard is applied to: – All patients, or – All screening test-positive patients and a subset (e.g. random 10%) of screening test-negative patients | Reference standard only applied to screen-positive patients |
Outcomes and target conditions | Diagnostic test accuracy: Number and proportion of people positive and negative on each test (TP, FP, TN, FN), sensitivity and specificity to screen for high-grade cervical lesions (CIN 2, CIN 3, HSIL), and/or invasive cervical cancer (squamous cell carcinoma or adenocarcinoma) | |
Timing of reference standard | Reference standard test performed before any management based on the index test result | |
Setting | Studies from Very High Human Development Index countries | |
Study design | – Observational studies (e.g. prospective or retrospective cohorts, or cross-sectional studies) in which all participants receive both the index and comparator screening test, followed by verification of disease status using the reference standard in all patients or in all screening test-positive patients and a subset (e.g. random 10%) of screening test-negative patients – Randomized controlled trials where participants are randomized to different screening tests but all receive the same reference standard | Conference proceedings; government reports; systematic reviews; case reports; case-control studies; editorials |
Language | English or French | |
Publication date | 1995–present |
Criteria | Inclusion | Exclusion |
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Population | Individuals with a cervix, or who have had their cervix removed as part of treatment for cervical cancer, 15 years of age and older (patients and the general public) Population subgroups: – Age (15–19, 20–24, 25–29, 30–69, 70+) – Risk groups: immunocompromised (e.g. HIV, organ transplantation, chemotherapy or chronic use of corticosteroids, use of disease-modifying anti-rheumatic drugs or biologics), risk behaviours (e.g. early sexual debut, women who have sex with women, individuals who have multiple sexual partners, smoking), Indigenous peoples, rural populations, immigrants, lower SES, pregnant individuals, HPV-vaccinated populations – Previous screening history (regular as per guidance vs. not regular (under) vs. never-screened) | |
Exposures | – Experience with critical outcome(s) related to screening or, – Exposure to clinical scenarios or information about potential critical outcomes and/or estimates of effect on outcome risks from screening, or – No experience or exposure to information about outcomes, but authors are soliciting probability trade-offs or ratings of different potential critical outcomes (e.g. number of biopsies acceptable to prevent one early diagnosis of invasive cervical cancer) – Focus of study is on consideration of possible, or assessment of experienced, outcomes from screening. Exposure moderators: differing descriptions or experience of outcomes in terms of stage, treatments received, severity, time since diagnosis (immediate vs. first year vs. later years); number of outcomes considered; differing estimates of magnitudes of effect from screening (if applicable) | Apart from studies with direct (e.g. time-trade off) or indirect (e.g. based on EQ-5D) measurement of heath state utilities, participants need to consider at least one outcome that may be a harm from screening (e.g. false positives, overdiagnosis [e.g. hrHPV+ but never will get cancer], increased CIN 2+ detection). Focus on the harms from management of lesions or cancer. |
Comparisons | – Different critical outcome or groups of outcomes (e.g. critical benefits vs. harms) – Healthy state without outcome (for utility studies) – No comparison (for utility studies) – No or another intervention, if applicable for interpreting outcome importance, i.e. no screening, another screening strategy (e.g. having different magnitude of effects), no information (e.g. in studies using decision aids). When only one arm (e.g. receiving decision aid) of a comparative study is used for interpreting data on patient preferences, the study will be classified as a non-comparative study. | |
Outcomes | a) Utility values/weights for the potential outcomes from screening b) Non-utility, quantitative information about relative importance of different outcomes (e.g. rating scales using ordinal or interval variables, ranking; preference for or against screening [screening attendance, intentions, or acceptance] or preferred screening strategy based on different outcome risk descriptions, strength of associations about outcome ratings with screening behaviours or intentions) c) Qualitative information indicating relative importance between outcomes d) Rank-order of importance of outcomes, based on data from a) to c) above, as applicable. Data must relate to the outcomes considered critical to the Task Force. Outcome groupings a) to c) above will be included in a hierarchical manner for each critical screening outcome. | |
Timing | Follow-up duration: any or none | |
Setting | Any setting in Very High Human Development Index countries | |
Study design and publication status | Any quantitative or qualitative study design using the methods described below: – Utility values/weights measured directly using time trade-offa, standard gambleb, visual analogue scales, conjoint analysis with choice experiments or probability trade-offs – Utility values/weights measured or estimated indirectly, e.g. from transforming several health state domains from multi-attribute utility indexes such as EQ-5D to utilities using general population preferences, including mapping from generic or disease-specific health-related quality of life instruments – Non-utility, quantitative information about relative importance of different outcomes, e.g. rating scales using ordinal or interval variables, ranking; preference for or against screening (screening attendance, intentions, or acceptance) or preferred screening strategy based on different outcome risk descriptions, strength of associations about outcome ratings with screening behaviours or intentions) – Qualitative information indicating relative importance between benefits and harms – Rank-order of importance of outcomes | Conference proceedings; government reports; editorials |
Language | English or French | |
Publication date | 2000–present |
Criterion | Inclusion | Exclusion |
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Population | Individuals with a cervix who would meet the criteria for cervical cancer screening, but who have never been screened or who have been under-screened, as defined by the study authors, when assessed against current screening recommendations (e.g. for screening interval). Population subgroups: – Indigenous peoples – Immigrant groups – Rural populations – Low socioeconomic status populations | Individuals with symptoms of cervical cancer or previous abnormal test results on cervical screening (unless cleared to return to normal screening) Individuals who have had complete surgical removal of the cervix |
Intervention | – Mail-out or opt-in (invitation to request) self-sampling for hrHPV screening – Other interventions aimed at individuals or primary care providers with the intent to increase acceptability of screening (e.g. screening reminders, education, counselling, provider recommendation, addressing cultural practices and beliefs, patient-provider communication) | Interventions not targeted to primary care providers or feasible for primary care to deliver to their patients (e.g. community or lay health workers, community distribution of HPV self-sampling kits) |
Comparator | – No intervention – Routine care (could include reminders or invitations to screen, or other forms of minimal intervention like pamphlets, posters) | |
Outcomes | Screening rate | |
Timing | No limitation on the duration of follow-up | |
Setting | – Primary care settings or settings available through primary care referral (note we will not exclude primary care interventions that are implemented alongside or in support of broader public health initiatives (e.g. reminders)) – Studies involving populations from Very High Development Index countries | |
Study design | – Randomized controlled trials – Non-randomized trials and cohort studies (will only be considered if there are no data available from randomized controlled trials) | Conference proceedings; government reports; case series; case reports; case-control studies; editorials |
Language | English or French | |
Publication date | 2000–present |