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The present update is a reassessment of the 2018 ‘Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil’ (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing.
The present update is a reassessment of the 2018 ‘Guidelines for HPV-DNA Testing for Cervical Cancer Screening in Brazil’ (Zeferino et al.)9, according to the changes observed in new international guidelines and knowledge updates. The most relevant and recent guidelines were assessed. Questions regarding the clinical practice were formulated, and the answers considered the perspective of the public and private sectors of the Brazilian health system. The review addressed risk-based strategies regarding age to start and stop screening, the use of cytology and colposcopy to support management decisions, treatment, follow-up strategies, and screening in specific groups, including vaccinated women. The update aims to improve the prevention of cervical cancer and to reduce overtreatment and the misuse of HPV testing.
ImportanceCervical cancer screening is associated with reduced cervical cancer mortality; however, clinical trials have also shown an association between excisional procedures for cervical neoplasia and an increased risk of preterm delivery (PTD). National screening guidelines must weigh adverse effects on birth outcomes against benefits of cancer prevention.ObjectiveTo ascertain the population-level association between the number of guideline-recommended cervical cancer screenings and downstream PTD risk among females aged 18 to 24 years.Design, Setting, and ParticipantsThis cross-sectional study used a difference-in-differences approach based on variation in the recommended number of cervical cancer screenings (over time and across individuals giving birth at different ages) to estimate the association between the cumulative recommended number of screenings (by the time of childbirth) and PTD risk. National Vital Statistics System data from females aged 18 to 24 years who had a singleton, nulliparous birth in the US between 1996 and 2018 were used. Regression models were adjusted for maternal educational level, race and ethnicity, comorbidities, marital status, and prenatal care visits. Data were analyzed between June 2020 and March 2023.ExposureA constructed variable capturing the cumulative number of guideline-recommended cervical cancer screenings for an individual based on their age and year of childbirth.Main Outcomes and MeasuresBinary indicators for PTD and very preterm delivery (VPTD), defined as delivery before 37 and 34 weeks’ gestational age, respectively, and gestational age was measured in weeks from the first day of the last menstrual period.ResultsAmong 11 333 151 females aged 18 to 24 years who gave birth between 1996 and 2018, 2 069 713 were Black (18.3%), 2 601 225 were Hispanic (23.0%), 6 068 498 were White (53.5%) individuals, and 593 715 (5.2%) were individuals of other race or ethnicity (Alaska Native; American Indian; Asian; Pacific Islander; multiracial; or unknown or missing race or ethnicity). Mean (SD) age was 20.9 (1.9) years, and 766 001 individuals (6.8%) had hypertension or diabetes. The mean (SD) number of guideline-recommended screenings by time of childbirth was 2.4 (2.2). Overall, PTD and VPTD occurred in 1 140 490 individuals (10.1%) and 333 040 (2.9%) of births, respectively. One additional recommended screening was associated with a 0.073 (95% CI, 0.026-0.120) percentage-point increase in PTD risk but no statistically significant change in VPTD risk. Females with hypertension or diabetes had a higher increase in PTD risk than those without these comorbidities (0.26 [95% CI, 0.11-0.4] vs 0.06 [95% CI, 0.01-0.10] percentage points; Wald test P < .001).Conclusions and RelevanceFindings of this cross-sectional study suggest that additional recommended cervical cancer screenings before birth were associated with an increased risk of PTD. These results can be used in future simulation models integrating oncological trade-offs to help ascertain optimal screening strategies.
IMPORTANCE Cervical cancer screening is a lifesaving intervention, with an array of approaches, including liquid-based cytology (LBC), molecular testing for human papillomavirus (HPV) infection, and combinations via parallel cotesting or sequential triage. Maximizing screening efficacy while minimizing overtreatment is vital, especially when considering how the HPV vaccine will affect the interpretation of results. OBJECTIVES To estimate the likely outcomes of different screening modalities and to model how the increasing uptake of the HPV vaccine could affect the interpretation of screening results. DESIGN, SETTING, AND PARTICIPANTS This decision analytic model established a simple Markov model to compare the outcomes of different cervical cancer screening modalities on a simulated population of women (aged Ն25 years), considering different levels of HPV vaccination. MAIN OUTCOMES AND MEASURES The number of cases of cervical intraepithelial neoplasia (CIN) grade 2 and 3 detected and missed, the number of false positives, and the number of tests required to achieve a given level of accuracy. Positive and negative predictive values of different modalities were simulated under varying levels of HPV vaccination and therefore HPV prevalence. RESULTS In a simulated population of 1000 women aged 25 years and older with an HPV prevalence of 2%, HPV-based modalities outperformed LBC-based approaches, detecting 19% more true positives (HPV test sensitivity, 89.9% [95% CI, 88.6%-91.1%]; LBC test sensitivity, 75.5% [95% CI, 66.6%-82.7%]). While cotesting markedly reduced missed cases, detecting 29% more true positives than LBC alone (19.5 [95% CI, 19.3-19.7] per 1000 women screened vs 15.1 [95% CI, 13.3-16.5] per 1000 women screened), it unacceptably increased excess colposcopy referral by 94% (184.4 [95% CI, 181.8-188.0] false positives per 1000 women screened vs 95.1 [95% CI, 93.1-97.0] false positives per 1000 women screened). By contrast, triage testing with reflex screening substantially reduced false positives by a factor of approximately 10 (eg, HPV with LBC triage, 9.6 [95% CI, 9.3-10.0] per 1000 women screened). Over a lifetime of screening, reflex approaches with appropriate test intervals maximized therapeutic efficacy; as HPV vaccination rates increased, HPV-based screening approaches resulted in fewer unnecessary colposcopies than LBC approaches (HPV testing, 80% vaccine coverage: 44.1 [95% CI, 40-45.9] excess colposcopies; LBC testing, 80% vaccine coverage: 96.9 [95% CI, 96.8-97.0] excess colposcopies). CONCLUSIONS AND RELEVANCEIn this decision analytic model, the effectiveness of cervical cancer screening was dependent on the prevalence of cervical dysplasia and/or HPV infection or vaccination in a population as well as the sensitivity and specificity of various modalities. Although screening is lifesaving, overtesting or modalities inappropriate to the target population may cause significant harm, including overtreatment.
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