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Objectives: Since 2006, the US human papillomavirus (HPV) vaccination program has led to decreases in HPV infections caused by high-risk vaccine-targeted HPV types (HPV 16/18). We assessed differences in high-risk HPV prevalence by cervical cytology result among 20- to 24-year-old persons participating in routine cervical cancer screening in 2015-2017 compared with 2007., Materials and Methods: Residual routine cervical cancer screening specimens were collected from 20- to 24-year-old members of 2 integrated healthcare delivery systems as part of a cross-sectional study and were tested for 37 HPV types. Cytology results and vaccination status (≥1 dose) were extracted from medical records. Cytology categories were normal, atypical squamous cells of undefined significance, low-grade squamous intraepithelial lesions (SIL), or high-grade SIL/atypical squamous cells cannot exclude high-grade SIL. Prevalences of HPV categories (HPV 16/18, HPV 31/33/45/52/58, HPV 35/39/51/56/59/66/68) were estimated by cytology result for 2007 and 2015-2017., Results: Specimens from 2007 (n = 4046) were from unvaccinated participants; 4574 of 8442 specimens (54.2%) from 2015-2017 were from vaccinated participants. Overall, HPV 16/18 positivity was lower in 2015-2017 compared with 2007 in all groups: high-grade SIL/atypical squamous cells cannot exclude high-grade SIL, 16.0% vs 69.2%; low-grade SIL, 5.4% vs 40.1%; atypical squamous cells of undefined significance, 5.0% vs 25.6%; and normal, 1.3% vs 8.1%. Human papillomavirus 31/33/45/52/58 prevalence was stable for all cytology groups; HPV 35/39/51/56/59/66/68 prevalence increased among low-grade SIL specimens (53.9% to 65.2%) but remained stable in other groups., Conclusions: Prevalence of vaccine-targeted high-risk HPV types 16/18 was dramatically lower in 2015-2017 than 2007 across all cytology result groups while prevalence of other high-risk HPV types was mainly stable, supporting vaccine impact with no evidence of type replacement., Competing Interests: A.L.N. has received research funding from Pfizer, Takeda, MedImmune, and Merck for unrelated studies. N.P.K. has received research funding from Merck, GlaxoSmithKline, Sanofi Pasteur, Novartis, MedImmune, Pfizer, and Protein Sciences (now Sanofi Pasteur) for unrelated studies. S.W. has received research funding from GlaxoSmithKline for an unrelated study. The other authors have declared they have no conflicts of interest., (Copyright © 2022, ASCCP.)

Background: Human papillomavirus (HPV) vaccine has been recommended in the United States since 2006 for routine vaccination of girls at age 11-12 years and through age 26 years for women not previously vaccinated. Changes in vaccine-type HPV (VT) prevalence can be used to evaluate vaccine impact, including herd effects., Methods: We determined type-specific HPV in cytology specimens from women aged 20-29 years screened for cervical cancer at Kaiser Permanente Northwest in 2007 and in two vaccine era periods: 2012-2013 and 2015-2016. Detection and typing used L1 consensus PCR with hybridization for 37 types, including quadrivalent vaccine types (HPV 6/11/16/18)., Results: Among 20-24 year-olds in 2012-2013 and 2015-2016, 44% and 64% had a history of ≥1-dose vaccination. VT prevalence decreased from 13.1% in 2007 to 2.9% in 2015-2016 (prevalence ratio [PR] = 0.22; 95% confidence interval [CI] 0.17-0.29). HPV 31 prevalence was also lower in the vaccine periods compared with 2007. VT prevalence in 2015-2016 among 20-24 year-olds was lower in both vaccinated, 1.3% (PR = 0.10; 95% CI 0.06-0.16), and unvaccinated women, 5.8% (PR = 0.45; 95% CI 0.33-0.61). Among 25-29 year-olds, 21% and 32% had a history of ≥1-dose vaccination. VT prevalence decreased from 8.1% in 2007 to 5.0% in 2015-2016 (PR = 0.62; 95% CI 0.50-0.78). Non-VT high risk prevalence was higher in the vaccine periods compared with the pre-vaccine era in both age groups, however, not in 2015-2016 compared with 2012-2013., Conclusion: Within 9-10 years of vaccine introduction, VT prevalence decreased 78% among 20-24 year-olds and 38% in 25-29 year-olds. There were declines in both vaccinated and unvaccinated women, showing evidence of direct and herd protection., (Published by Elsevier Ltd.)

Objective: To examine whether surgical procedures involving the uterine cervix were associated with pregnancy outcomes, including preterm birth, low birth weight, cesarean delivery and pregnancy loss., Design: Population-based observational study nested in retrospective matched cohort., Setting: Kaiser Permanente Northwest integrated health plan in Oregon/Washington, U.S.A., Population: Female health plan members age 14-53 years with documented pregnancies from 1998-2009. Women with prior excisional and ablative cervical surgical procedures (N = 322) were compared to women unexposed to cervical procedures (N = 4,307) and, separately, to those having undergone only diagnostic/biopsy procedures (N = 847)., Methods: Using log-linear regression models, we examined risk of adverse pregnancy outcomes in relation to prior excisional or ablative cervical surgical procedures. We stratified excisional procedures by excision thickness. We evaluated for confounding by age, body mass index, race, smoking history, previous preterm birth, and parity., Results: We found a positive association between excisional treatment > = 1.0 cm and the outcomes preterm birth and low birth weight (preterm birth unadjusted risk ratio [RR] = 2.15, 95% confidence interval [CI] 1.16-3.98 for excisions ≥1.0 cm compared to unexposed women), particularly in women who delivered within one year of surgery (RR = 3.26, 95% CI 1.41-7.53). There was no clear association between excisional treatment and cesarean delivery, and treated women did not have a substantially higher risk of dysfunctional labor. Ablative treatment was not associated with low birth weight, preterm birth, or cesarean delivery but was associated with pregnancy loss (RR = 1.43, 95% CI 1.05-1.93 vs. unexposed women). Analyses using the diagnostic procedures comparison group produced similar results., Conclusion: Women with > = 1.0 cm excisional treatment had elevated risk of preterm birth and low birth weight when compared to unexposed women and women with cervical diagnostic procedures. This suggests that increased risk derives from the treatment itself, not from other characteristics. The observed association between pregnancy loss and ablative surgical treatment requires further investigation., Competing Interests: S Weinmann, A Naleway, E Myers, G Swamy (and/or their institutions) received funding from the GSK group of companies to complete the work disclosed in this manuscript (for study design, model development, statistical analysis). G Swamy declares to have received consulting and lecturing fees and grant support for vaccine studies from GSK, as well as for advisory boards, lectures, and the development of educational presentations. E Myers declares to have received consulting fees from the GSK group of companies, Merck and Gen-Probe. G Krishnarajah, B Arondekar and J Fernandez were employees of the GSK group of companies at the time of the study conduct and own restricted shares/stocks of the GSK group of companies. G Krishnarajah is currently employed by CSL and also reports ownership of stock options/restricted shares from CSL. B Arondekar is currently employed by Pfizer. J Fernandez is currently employed by Takeda and also reports ownership of stock options/restricted shares from Takeda. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cervical cancer screening and follow-up guidelines have changed considerably in recent years, but to the authors' knowledge few published reports exist to estimate the impact of these changes in community-based settings. The authors examined the patterns and results of cervical cancer testing and follow-up over a decade in 4 geographically diverse US health care systems to inform the future evaluation of changes resulting from increased uptake of the human papillomavirus (HPV) vaccination., Methods: The authors studied women aged 21 to 65 years who were members of one of these health systems at any time between 1998 and 2007. Data were collected and standardized across sites, based on receipt of Papanicolaou (Pap) and HPV tests, HPV vaccination, cervical biopsies, and treatment of cervical dysplasia. Annual rates (per 1000 person-years) of Pap testing, HPV testing, and cervical biopsy and treatment procedures were calculated. Screening intervals and trends in the results of screening Pap tests and cervical biopsies also were examined., Results: Pap testing rates decreased (from 483 per 1000 person-years in 2000 to 412 per 1000 person-years in 2007) and HPV testing rates increased over the study period. Screening frequency varied across health care systems, and many women continued to receive annual testing. All 4 sites moved to less frequent screening over the study period without marked changes in the overall use of cervical biopsy or treatment., Conclusions: Despite differences over time and across health plans in rates of cervical cancer testing and follow-up cervical procedures, the authors found no notable differences in Pap test results, diagnostic or treatment procedure rates, or pathological outcomes. This finding suggests that the longer screening intervals did not lead to more procedures or more cancer diagnoses., (© 2015 American Cancer Society.)

Objective: To determine whether treatments for precancerous cervical lesions were associated with lower pregnancy rates compared to rates in unexposed women and women who had a diagnostic cervical biopsy or colposcopy., Design: Matched, retrospective cohort study., Setting: Kaiser Permanente Northwest (KPNW), an integrated healthcare delivery system in Oregon and Washington., Patients: Women 14 to 53 years old with KPNW enrollment during the period 1998 through 2009., Main Outcome Measure: Pregnancy after exposure or index date. Pregnancy was defined using a validated algorithm and electronic medical records data., Results: We observed 570 pregnancies following cervical treatment in 4,137 women, 1,533 pregnancies following a diagnostic procedure in 13,767 women, and 7,436 pregnancies in a frequency-matched sample of 81,435 women unexposed to treatment or diagnostic procedures. After adjusting for age and contraceptive use, we observed a higher rate of pregnancies in the treatment group compared to unexposed women (hazard ratio (HR) = 1.42, 95% confidence interval (CI): 1.30-1.55), but no difference in pregnancy rates between the treatment and diagnostic procedure groups (HR = 1.03, 95% CI: 0.93-1.13)., Conclusions: No adverse effects of cervical procedures on subsequent rates of pregnancy were observed in this cohort with up to twelve years of follow-up time.

Background: To the authors' knowledge, few studies to date have examined adherence to recommended guidelines for follow-up and outcomes after an unsatisfactory Papanicolaou (Pap) test (UPT) with liquid-based technologies., Methods: Within 4 US health plans, the median time to follow-up and the percentage of patients with follow-up testing by 120 days was calculated after a UPT. Multivariable analyses evaluated the association between clinical factors and follow-up testing. The authors compared the risk of a diagnosis of cervical intraepithelial neoplasia of type 2 or worse (CIN2+) after a UPT with the risk after a satisfactory Pap test while controlling for study site, test year, and other covariates., Results: A total of 634,644 Pap tests performed between 2004 and 2010 were included in the current study. Of 1442 UPTs, 53.4% had follow-up testing within 120 days; follow-up differed across the health plans (P<.001) and was found to be higher among patients aged <50 years (57.2% vs 48.8%; P = .01) and those with positive human papillomavirus (HPV) results (84.6% vs 53.9; P <.01). The risk of CIN2+ was similar for patients with both unsatisfactory and satisfactory Pap tests. However, after a UPT, the variables of age <50 years, having no previous history of Pap testing, having a history of a previous abnormal Pap test, and positive HPV status were all found to be risk factors for CIN2+; a positive HPV test was found to be the strongest risk factor for developing CIN2+. A negative HPV test result was protective for a CIN2+ diagnosis., Conclusions: Various clinical factors associated with the risk of CIN2+ appear to influence the receipt of follow-up after a UPT. HPV test results in patients with UPTs might be used in follow-up strategies; specifically, a negative test result might reduce the urgency for repeat Pap testing., (© 2015 American Cancer Society.)

Recent research suggests that cervical screening of older women is associated with a considerable decrease in cervical cancer incidence. We sought to quantify the efficacy of cervical cytology screening to reduce death from this disease. Among enrollees of 2 US health plans, we compared Papanicolaou smear screening histories of women aged 55-79 years who died of cervical cancer during 1980-2010 (cases) to those of women at risk of cervical cancer (controls). Controls were matched 2:1 to cases on health plan, age, and enrollment duration. Cytology screening during the detectable preclinical phase, estimated as the 5-7 years before diagnosis during which cervical neoplasia is asymptomatic but cytologically detectable, was ascertained from medical records. A total of 39 cases and 80 controls were eligible. The odds ratio of cervical cancer death associated with screening during the presumed detectable preclinical phase was 0.26 (95% confidence interval: 0.10, 0.63) after adjustment for matching characteristics, smoking, marital status, and race/ethnicity using logistic regression. We estimate that cervical cytology screening of all women aged 55-79 years in the United States could avert 630 deaths annually. These results provide a minimum estimate of the efficacy of human papillomavirus DNA screening-a more sensitive test-to reduce cervical cancer death among older women.

Background: Papanicolaou (Pap) testing has transitioned from conventional preparations (CPs) to liquid-based preparations (LBPs) because of the perceived superiority of LBPs. Many studies conclude that LBPs reduce unsatisfactory Pap tests; however, some believe that the evidence substantiating this claim is weak. The authors studied the effect of the transition from CPs to LBPs on the proportion of unsatisfactory Pap tests in 4 health care systems in the United States participating in the National Institutes of Health-funded Screening Effectiveness and Research in Community-Based Healthcare (SEARCH) project., Methods: The study cohort consisted of 548,174 women ages 21 to 65 years who had 1443,725 total Pap tests between 2000 and 2010. Segmented regression analysis was used to estimate the effect of adopting LBPs on the proportion of unsatisfactory Pap tests after adjusting for age., Results: Three sites that implemented SurePath LBP experienced significant reductions in unsatisfactory Pap tests (estimated effect: site 1, -2.46%; 95% confidence interval [CI], -1.47%, -3.45%; site 2, -1.78%; 95% CI, -1.54%, -2.02%; site 3, -8.25%; 95% CI, -7.33%, -9.17%). The fourth site that implemented ThinPrep LBP did not experience a reduction in unsatisfactory Pap tests. The relative risk of an unsatisfactory Pap test in women aged ≥ 50 years increased after the transition to LBPs (SurePath: relative risk, 2.1; 95% CI, 1.9-2.2; ThinPrep: relative risk, 1.7; 95% CI, 1.5-2.0)., Conclusions: The observed changes in the proportion of unsatisfactory Pap tests varied across the participating sites and depended on the type of LBP technology, the age of women, and the rates before the implementation of this technology., (© 2013 American Cancer Society.)

Background: Although the effectiveness of cervical cancer screening has been firmly established in reproductive-age women, its usefulness in older women is unclear. We sought to evaluate the efficacy of cervical cancer screening in older women., Methods: We conducted a case-control study within two integrated health care systems in the northwestern United States. Cases (n = 69) were women aged 55-79 years who were diagnosed with invasive cervical cancer during 1980-1999. Controls (n = 208) were women with an intact uterus and no diagnosis of cervical cancer, but otherwise similar to cases in terms of age and length of enrollment in the health plan. We reviewed medical records to ascertain screening history during the 7 years prior to reference date., Results: Compared to cases, controls were more likely to have received a Pap test. After adjustment for age and current smoking status, screening prior to an estimated 1-year duration of the occult invasive phase of cervical cancer was associated with a substantial reduction in risk [odds ratio (OR) 0.23; 95% CI 0.11-0.44]. Similar results were obtained using different estimates of the duration of the occult invasive phase. Analysis of the relative incidence of invasive cervical cancer in relation to the time following a negative screening test suggested a large reduction during the first year (OR 0.09; 95% CI 0.03-0.24). The incidence remained low for several years thereafter, returning to the incidence among unscreened women after 5-7 years., Conclusions: Cervical cancer screening by means of cytology is highly efficacious in older women. Our findings also suggest that five-yearly screening is approximately as efficacious as more frequent screening.

Background: Cervical intraepithelial neoplasia grade 3+ (CIN3+) and adenocarcinoma in situ incidence will be an important measure of HPV vaccine impact. Integrated healthcare delivery systems, such as Kaiser Permanente, could be used to monitor CIN3+ trends; however, limited evaluations of data from healthcare delivery systems for CIN3+ surveillance exist., Methods: We compared CIN3+ diagnoses by ICD-9 code with CIN3+ diagnoses by pathology results among 121,211 females aged 11 to 30 years who were continuously enrolled from 2000 to 2005 in either Kaiser Permanente Northern California or Kaiser Permanente Northwest. We calculated sensitivity and positive predictive value of diagnosis by ICD-9 codes using pathology CIN3+ diagnosis as the gold standard., Results: There were 1,090 women with at least one CIN3+ diagnosis by ICD-9 code 233.1 and 1,200 women with at least one CIN3+ diagnosis by pathology results. The sensitivity of the ICD-9 code for detecting a woman with at least one pathology diagnosis for CIN3+ was 62% (740/1,200); positive predictive value was 68% (740/1,090). Among women with at least one CIN3+ diagnosis by ICD-9 code, 679 (62%) had more than one visit with this code; whereas, among women with at least one CIN3+ diagnosis by pathology, 466 (39%) had more than one CIN3+ pathology result., Conclusions: ICD-9 codes may underestimate the number of women with at least one CIN3+ diagnosis., Impact: Pathology results, when available, may provide better estimates of CIN3+ incidence.

Purpose: Two human papillomavirus (HPV) vaccines are available to prevent cervical cancer. One early measure of HPV vaccine impact would be a reduction in vaccine-related HPV types (HPV 6, 11, 16, or 18, or HPV 16, 18) in cervical samples from young women. We aimed to assess feasibility of specimen collection and baseline HPV prevalence in an integrated healthcare delivery system., Methods: Residual cervical specimens collected during routine cervical cancer screening (2006-2008) were retained consecutively from eligible females aged 11-29 years, stratified by age group. Specimens were evaluated for 37 HPV genotypes using the Roche Linear Array assay., Results: Of 10,124 specimens submitted, 10,103 (99 %) were adequate for HPV testing. Prevalence of HPV 6, 11, 16, or 18 genotype was 11.4 % overall and was the highest in the youngest age group (18.1 % in the 11-19-year-olds, 12.5 % in the 20-24-year-olds, and 7.0 % in the 25-29-year-olds)., Conclusions: HPV types 6, 11, 16, or 18 prevalence could be measured over time to assess early HPV vaccine impact using residual specimens from an integrated healthcare delivery system, particularly if sampling focused on young women.

Background: Invasive cervical cancer is highly preventable, yet it continues to occur, even among women who have access to cancer screening and treatment services. To reduce cervical cancer among such women, reasons for its occurrence must be better understood. We examined factors associated with the diagnosis of cervical cancer among women enrolled in health plans., Methods: We identified all cases of invasive cervical cancer (n = 833) diagnosed from January 1, 1995, through December 31, 2000, among women who were long-term members of seven prepaid comprehensive health plans and reviewed each woman's medical records for the 3 years prior to her cancer diagnosis. Women were classified into one of three categories based on Pap test histories 4-36 months before diagnosis: failure to screen with a Pap test, failure in detection by a Pap test, or failure in follow-up of an abnormal test result., Results: The majority of cases (n = 464; 56%) were in women who had no Pap tests during the period 4-36 months prior to diagnosis. Of the remaining cases, 263 (32%) were attributed to Pap test detection failure and 106 (13%) to follow-up failure. Being older (odds ratio [OR] = 6.48, 95% confidence interval [CI] = 3.89 to 10.79) or living in an area of higher poverty (OR = 1.72, 95% CI = 1.11 to 2.67) or having a lower education level (OR= 1.52; 95% CI = 1.07 to 2.16) was associated with the likelihood of being assigned to the failure to screen category versus either of the other two categories. A total of 375 (81%) of the 464 patients who had not had Pap screening had had at least one outpatient visit 4-36 months prior to cancer diagnosis. The cancer diagnostic process was triggered by a routine screening examination in 44% of patients, whereas 53% of the patients presented with symptoms consistent with cervical cancer; the remaining 3% were identified fortuitously during the course of receiving noncervical care., Conclusions: To reduce the incidence of invasive cervical cancer among women with access to screening and treatment, Pap screening adherence should be increased. In addition, strategies to improve the accuracy of Pap screening could afford earlier detection of cervical cancer.

Objective: To describe the systems strategies used to reduce failures in delivery of breast and cervical cancer screening services in HMOs with high performance rates for these services., Study Design: Multiple case study., Participants and Methods: Seven HMOs participated in an assessment of their breast and cervical cancer screening policies and procedures. Current clinical practice guidelines were analyzed, and key informants were interviewed about organizational policies and procedures that ensure initial screening and follow-up of abnormal results. Data were analyzed across plans for several theoretically relevant domains, including leadership and policies, clinical decision support, delivery system design, clinical information systems, and patient self-management support., Results: Practice guidelines were fundamentally similar across plans for both cancer screenings, although operationalization of risk and formatting of the written documents differed. These plans adopted a wide array of strategies, particularly in the clinical decision support, clinical information systems, and patient self-management support domains, but there is room for improvement. Differences among plans and between strategies for breast and cervical cancer screening provide new understanding of how to approach this problem., Conclusions: Organizations seeking to improve performance of breast and cervical cancer screening should consider multiple strategies aimed at multiple targets and should ensure that strategies used for one type of cancer are considered for others.