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BackgroundThe majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high-risk populations.MethodsThe authors analyzed the interobserver reproducibility of anal cytology in a population of 363 human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Liquid-based cytology (LBC) specimens were collected in the anal dysplasia clinic before the performance of high-resolution anoscopy on all patients. Papanicolaou-stained LBC slides were evaluated by 2 cytopathologists, each of whom was blinded to the clinical outcome and the other pathologist's results, using the revised Bethesda terminology.ResultsOverall agreement between the 2 observers was 66% (kappa, 0.54; linear-weighted kappa, 0.69). Using dichotomizing cytology results (atypical squamous cells of undetermined significance [ASC-US] or worse vs less than ASC-US), the agreement increased to 86% (kappa, 0.69). An increasing likelihood of testing positive for markers associated with HPV-related transformation, p16/Ki-67, and HPV oncogene messenger RNA was observed, with increasing severity of cytology results noted both for individual cytologists and for consensus cytology interpretation (P value for trend [p(trend)] < .0001 for all).ConclusionsModerate to good agreement was observed between 2 cytopathologists evaluating anal cytology samples collected from HIV-positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancerous lesions. Anal cytology may be used for anal cancer screening in high-risk populations, and biomarkers of HPV-related transformation can serve as quality control for anal cytology.

The World Health Organization Call to Eliminate Cervical Cancer resonates in cities like Manaus, Brazil, where the burden is among the world's highest. Manaus has offered free cytology-based screening since 1990 and HPV immunization since 2013, but the public system is constrained by many challenges and performance is not well-defined. We obtained cervical cancer prevention activities within Manaus public health records for 2019 to evaluate immunization and screening coverage, screening by region and neighborhood, and the annual Pink October screening campaign. We estimated that among girls and boys age 14–18, 85.9% and 64.9% had 1+ doses of HPV vaccine, higher than rates for age 9–13 (73.4% and 43.3%, respectively). Of the 90,209 cytology tests performed, 24.9% were outside the target age and the remaining 72,230 corresponded to 40.1% of the target population (one-third of women age 25–64). The East zone had highest screening coverage (49.1%), highest high-grade cytology rate (2.5%) and lowest estimated cancers (38.1/100,000) compared with the South zone (32.9%, 1.8% and 48.5/100,000, respectively). Largest neighborhoods had fewer per capita screening locations, resulting in lower coverage. During October, some clinics successfully achieved higher screening volumes and high-grade cytology rates (up to 15.4%). Although we found evidence of some follow-up within 10 months post-screening for 51/70 women (72.9%) with high-grade or worse cytology, only 18 had complete work-up confirmed. Manaus has successfully initiated HPV vaccination, forecasting substantial cervical cancer reductions by 2050. With concerted efforts during campaigns, some clinics improved screening coverage and reached high-risk women. Screening campaigns in community locations in high-risk neighborhoods using self-collected HPV testing can achieve widespread coverage. Simplifying triage and treatment with fewer visits closer to communities would greatly improve follow-up and program effectiveness. Achieving WHO Cervical Cancer Elimination goals in high-burden cities will require major reforms for screening and simpler follow-up and treatment. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus vaccination and cervical screening are lacking in most lower resource settings, where approximately 80% of more than 500 000 cancer cases occur annually. Visual inspection of the cervix following acetic acid application is practical but not reproducible or accurate. The objective of this study was to develop a "deep learning"-based visual evaluation algorithm that automatically recognizes cervical precancer/cancer.Methods: A population-based longitudinal cohort of 9406 women ages 18-94 years in Guanacaste, Costa Rica was followed for 7 years (1993-2000), incorporating multiple cervical screening methods and histopathologic confirmation of precancers. Tumor registry linkage identified cancers up to 18 years. Archived, digitized cervical images from screening, taken with a fixed-focus camera ("cervicography"), were used for training/validation of the deep learning-based algorithm. The resultant image prediction score (0-1) could be categorized to balance sensitivity and specificity for detection of precancer/cancer. All statistical tests were two-sided.Results: Automated visual evaluation of enrollment cervigrams identified cumulative precancer/cancer cases with greater accuracy (area under the curve [AUC] = 0.91, 95% confidence interval [CI] = 0.89 to 0.93) than original cervigram interpretation (AUC = 0.69, 95% CI = 0.63 to 0.74; P < .001) or conventional cytology (AUC = 0.71, 95% CI = 0.65 to 0.77; P < .001). A single visual screening round restricted to women at the prime screening ages of 25-49 years could identify 127 (55.7%) of 228 precancers (cervical intraepithelial neoplasia 2/cervical intraepithelial neoplasia 3/adenocarcinoma in situ [AIS]) diagnosed cumulatively in the entire adult population (ages 18-94 years) while referring 11.0% for management.Conclusions: The results support consideration of automated visual evaluation of cervical images from contemporary digital cameras. If achieved, this might permit dissemination of effective point-of-care cervical screening. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV)-related biomarkers have shown good cross-sectional performance for anal precancer detection in human immunodeficiency virus–positive (HIV+) men who have sex with men (MSM). However, the long-term performance and risk stratification of these biomarkers are unknown. Here, we prospectively evaluated high-risk (HR) HPV DNA, HPV16/18 genotyping, HPV E6/E7 messenger RNA (mRNA), and p16/Ki-67 dual stain in a population of HIV+ MSM. Methods We enrolled 363 HIV+ MSM between 2009–2010, with passive follow-up through 2015. All had anal cytology and a high-resolution anoscopy at baseline. For each biomarker, we calculated the baseline sensitivity and specificity for a combined endpoint of high-grade squamous intraepithelial lesion (HSIL) and anal intraepithelial neoplasia grade 2 or more severe diagnoses (HSIL/AIN2+), and we estimated the 2- and 5-year cumulative risks of HSIL/AIN2+ using logistic and Cox regression models. Results There were 129 men diagnosed with HSIL/AIN2+ during the study. HR-HPV testing had the highest positivity and sensitivity of all assays, but the lowest specificity. HPV16/18 and HPV E6/E7 mRNA had high specificity, but lower sensitivity. The 2- and 5-year risks of HSIL/AIN2+ were highest for those testing HPV16/18- or HPV E6/E7 mRNA–positive, followed by those testing dual stain–positive. Those testing HR-HPV– or dual stain–negative had the lowest 2- and 5-year risks of HSIL/AIN2+. Conclusions HPV-related biomarkers provide long-term risk stratification for anal precancers. HR-HPV– and dual stain–negativity indicate a low risk of HSIL/AIN2+ for at least 2 years, compared with negative anal cytology; however, the high positivity of HR-HPV in HIV+ MSM may limit its utility for surveillance and management in this population. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is caused by persistent human papillomavirus (HPV) infection. US consensus management guidelines for a positive cervical screening result typically focus on the current screening result only. A negative testing history may alter risk of the following positive screening results, caused by a new HPV infection, and therefore its optimal management.Methods: Women ages 30 years and older were screened with triennial HPV and cytology co-testing at Kaiser Permanente Northern California from 2003 to 2014. We estimated the subsequent 5-year risks of cervical intraepithelial neoplasia grade 3 or more severe diagnoses (CIN3+) in a cohort of 1 156 387 women following abnormal (atypical squamous cells of undetermined significance [ASC-US] or worse) cytology and/or positive HPV testing, when the test result followed 0 (n = 990 013), 1 (n = 543 986), 2 (n = 245 974), or 3 (n = 79 946) consecutive negative co-test(s). All statistical tests were two-sided.Results: Following 0-3 successive negative co-tests, 5-year CIN3+ risks following a positive HPV test decreased progressively from 7.2% (95% CI = 7.0% to 7.4%) to 1.5% (95% CI = 0.7% to 3.4%) (Ptrend < .001). Similarly, risks following an abnormal (ASC-US or worse) cytology result decreased from 6.6% (95% CI = 6.4% to 6.9%) to 1.1% (95% CI = 0.5% to 2.3%) (Ptrend < .001). Risks following low-grade squamous intraepithelial lesion, the risk threshold for referral to colposcopy in the United States, decreased from 5.2% (95% CI = 4.7% to 5.7%) to 0.9% (95% CI = 0.2% to 4.3%). Risks following high-grade squamous intraepithelial lesion or more severe, a specific marker for the presence of precancerous lesions, decreased from 50.0% (95% CI = 47.5% to 52.5%) to 10.0% (95% CI = 2.6% to 34.4%).Conclusions: Following one or more sequential antecedent, documented negative co-tests or HPV tests, women with HPV-positive ASC-US or low-grade squamous intraepithelial lesion might have sufficiently low CIN3+ risk that they do not need colposcopy referral and might instead undergo 6-12-month surveillance for evidence of higher risk before being referred to colposcopy. [ABSTRACT FROM AUTHOR]

Background: State-of-the-art cervical cancer prevention includes human papillomavirus (HPV) vaccination among adolescents and screening/treatment of cervical precancer (CIN3/AIS and, less strictly, CIN2) among adults. HPV testing provides sensitive detection of precancer but, to reduce overtreatment, secondary "triage" is needed to predict women at highest risk. Those with the highest-risk HPV types or abnormal cytology are commonly referred to colposcopy; however, expert cytology services are critically lacking in many regions.Methods: To permit completely automatable cervical screening/triage, we designed and validated a novel triage method, a cytologic risk score algorithm based on computer-scanned liquid-based slide features (FocalPoint, BD, Burlington, NC). We compared it with abnormal cytology in predicting precancer among 1839 women testing HPV positive (HC2, Qiagen, Germantown, MD) in 2010 at Kaiser Permanente Northern California (KPNC). Precancer outcomes were ascertained by record linkage. As additional validation, we compared the algorithm prospectively with cytology results among 243 807 women screened at KPNC (2016-2017). All statistical tests were two-sided.Results: Among HPV-positive women, the algorithm matched the triage performance of abnormal cytology. Combined with HPV16/18/45 typing (Onclarity, BD, Sparks, MD), the automatable strategy referred 91.7% of HPV-positive CIN3/AIS cases to immediate colposcopy while deferring 38.4% of all HPV-positive women to one-year retesting (compared with 89.1% and 37.4%, respectively, for typing and cytology triage). In the 2016-2017 validation, the predicted risk scores strongly correlated with cytology (P < .001).Conclusions: High-quality cervical screening and triage performance is achievable using this completely automated approach. Automated technology could permit extension of high-quality cervical screening/triage coverage to currently underserved regions. [ABSTRACT FROM AUTHOR]

Background: The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs.Methods: We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided.Results: HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed.Conclusions: The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women. [ABSTRACT FROM AUTHOR]

Background: Current U.S. cervical cancer screening and management guidelines do not consider previous screening history, because data on multiple-round human papillomavirus (HPV) and cytology "co-testing" have been unavailable.Objective: To measure cervical cancer risk in routine practice after successive negative screening co-tests at 3-year intervals.Design: Observational cohort study.Setting: Integrated health care system (Kaiser Permanente Northern California, Oakland, California).Patients: 990 013 women who had 1 or more co-tests from 2003 to 2014.Measurements: 3- and 5-year cumulative detection of (risk for) cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, and cervical cancer (≥CIN3) in women with different numbers of negative co-tests, overall and within subgroups defined by previous co-test results or baseline age.Results: Five-year ≥CIN3 risks decreased after each successive negative co-test screening round (0.098%, 0.052%, and 0.035%). Five-year ≥CIN3 risks for an HPV-negative co-test, regardless of the cytology result, nearly matched the performance (reassurance) of a negative co-test for each successive round of screening (0.114%, 0.061%, and 0.041%). By comparison, ≥CIN3 risks for the cytology-negative co-test, regardless of the HPV result, also decreased with each successive round, but 3-year risks were as high as 5-year risks after an HPV-negative co-test (0.199%, 0.065%, and 0.043%). No interval cervical cancer cases were diagnosed after the second negative co-test. Independently, ≥CIN3 risks decreased with age. Length of previous screening interval did not influence future ≥CIN3 risks.Limitation: Interval-censored observational data.Conclusion: After 1 or more negative cervical co-tests (or HPV tests), longer screening intervals (every 5 years or more) might be feasible and safe.Primary Funding Source: National Cancer Institute Intramural Research Program. [ABSTRACT FROM AUTHOR]

HPV testing is more sensitive than cytology for cervical screening. However, to incorporate HPV tests into screening, risk-stratification ('triage') of HPV-positive women is needed to avoid excessive colposcopy and overtreatment. We prospectively evaluated combinations of partial HPV typing (Onclarity, BD) and cytology triage, and explored whether management could be simplified, based on grouping combinations yielding similar 3-year or 18-month CIN3+ risks. We typed ∼9,000 archived specimens, taken at enrollment (2007-2011) into the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression (PaP) cohort. Stratified sampling, with reweighting in the statistical analysis, permitted risk estimation of HPV/cytology combinations for the 700,000+-woman KPNC screening population. Based on 3-year CIN3+ risks, Onclarity results could be combined into five groups (HPV16, else HPV18/45, else HPV31/33/58/52, else HPV51/35/39/68/56/66/68, else HPV negative); cytology results fell into three risk groups ('high-grade,' ASC-US/LSIL, NILM). For the resultant 15 HPV group-cytology combinations, 3-year CIN3+ risks ranged 1,000-fold from 60.6% to 0.06%. To guide management, we compared the risks to established 'benchmark' risk/management thresholds in this same population ( e.g., LSIL predicted 3-year CIN3+ risk of 5.8% in the screening population, providing the benchmark for colposcopic referral). By benchmarking to 3-year risk thresholds (supplemented by 18-month estimates), the widely varying risk strata could be condensed into four action bands (very high risk of CIN3+ mandating consideration of cone biopsy if colposcopy did not find precancer; moderate risk justifying colposcopy; low risk managed by intensified follow-up to permit HPV 'clearance'; and very low risk permitting routine screening.) Overall, the results support primary HPV testing, with management of HPV-positive women using partial HPV typing and cytology. [ABSTRACT FROM AUTHOR]

Three different cervical screening methods [cytology, human papillomavirus(HPV) testing and visual inspection with acetic acid(- VIA)] are being considered in China for the national cervical screening program. Comparing risks of CIN3 and cervical cancer (CIN3+) for different results can inform test choice and management guidelines. We evaluated the immediate risk of CIN3+ for different screening results generated from individual and combined tests. We compared tests using a novel statistic designed for this purpose called Mean Risk Stratification (MRS), in a pooled analysis of 17 cross sectional population-based studies of 30,371 Chinese women screened with all 3 methods and diagnosed by colposcopically-directed biopsies. The 3 tests combined powerfully distinguished CIN3+ risk; triple-negative screening conferred a risk of 0.01%, while HPV-positive HSIL+ that was VIA-positive yielded a risk of 57.8%. Among the three screening tests, HPV status most strongly stratified CIN3+ risk. Among HPV-positive women, cytology was the more useful second test. In HPV-negative women, the immediate risks of CIN3+ ranged from 0.01% (negative cytology), 0.00% (ASC-US), 1.1% (LSIL), to 6.6 (HSIL+). In HPV-positive women, the CIN3+ risks were 0.9% (negative cytology), 3.6% (ASC-US), 6.3% (LSIL) and 38.5% (HSIL+). VIA results did not meaningful stratify CIN3+ risk among HPV-negative women with negative or ASC-US cytology; however, positive VIA substantially elevated CIN3+ risk for all other, more positive combinations of HPV and cytology compared with a negative VIA. Because all 3 screening tests had independent value in defining risk of CIN3+, different combinations can be optimized as pragmatic strategies in different resource settings. [ABSTRACT FROM AUTHOR]

It is unclear whether a woman's age influences her risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) upon detection of HPV. A large change in risk as women age would influence vaccination and screening policies. Among 972,029 women age 30-64 undergoing screening with Pap and HPV testing (Hybrid Capture 2, Qiagen, Germantown, MD) at Kaiser Permanente Northern California (KPNC), we calculated age-specific 5-year CIN3+ risks among women with HPV infections detected at enrollment, and among women with 'newly detected' HPV infections at their second screening visit. Women (57,899, 6.0%) had an enrollment HPV infection. Among the women testing HPV negative at enrollment with a second screening visit, 16,724 (3.3%) had a newly detected HPV infection at their second visit. Both enrollment and newly detected HPV rates declined with age ( p < 0.001). Women with enrollment versus newly detected HPV infection had higher 5-year CIN3+ risks: 8.5% versus 3.9%, ( p < 0.0001). Risks did not increase with age but declined slightly from 30-34 years to 60-64 years: 9.4% versus 7.4% ( p = 0.017) for enrollment HPV and 5.1% versus 3.5% ( p = 0.014) for newly detected HPV. Among women age 30-64 in an established screening program, women with newly detected HPV infections were at lower risk than women with enrollment infections, suggesting reduced benefit vaccinating women at older ages. Although the rates of HPV infection declined dramatically with age, the subsequent CIN3+ risks associated with HPV infection declined only slightly. The CIN3+ risks among older women are sufficiently elevated to warrant continued screening through age 65. [ABSTRACT FROM AUTHOR]

BACKGROUND Different US practice guidelines have conflicting recommendations for when women should return after a screening result of human papillomavirus (HPV)-negative with an equivocal Papanicolaou (Pap) result of atypical squamous cells of undetermined significance (ASC-US) (ie, return in either 3 or 5 years). One way to determine management is to compare the risk of precancer/cancer after an HPV-negative/ASC-US result with the risks after other negative screening results. For example, if the risk after an HPV-negative/ASC-US result was similar to the risk after a negative Pap test, a 3-year return would be preferred because guidelines agree that women with negative Pap test results should return in 3 years. Alternatively, if the risk after an HPV-negative/ASC-US result is similar to that after a cotest-negative result (HPV negative/Pap test negative), a 5-year return would be preferred because guidelines agree that women testing cotest negative should return in 5 years. METHODS The authors compared risks of cervical intraepithelial neoplasia of grade 3 or higher (CIN3+) and cervical cancer among women aged 30 years to 64 years at Kaiser Permanente Northern California with the following test results from 2003 through 2012: 17,191 women testing HPV negative/ASC-US; 980,268 women testing Pap test negative (regardless of HPV result); and 892,882 women testing cotest negative. RESULTS The 5-year CIN3+ and cancer risks after an HPV-negative/ASC-US result were closer to the risks after a negative Pap test result (CIN3+: 0.48% vs 0.31% [ P =.0019]; and cancer: 0.043% vs 0.031% [ P =.4]) than after a negative cotest (CIN3+: 0.48% vs 0.11% [ P<.0001]; and cancer: 0.043% vs 0.014% [ P =.016]). CONCLUSIONS Women testing HPV negative/ASC-US were found to have precancer/cancer risks that were more closely aligned with women with negative Pap test results, suggesting that women testing HPV negative/ASC-US should be managed similarly to women testing negative on Pap tests with a 3-year return for screening. Cancer (Cancer Cytopathol) 2014;122:842-850. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

To inform the proposed systematic adjudicative staining of cervical intraepithelial neoplasia grade 2 (CIN2) and equivocal diagnoses, we characterized diagnostic heterogeneity across 15 laboratories. Laboratory-specific distributions of 37,486 biopsy specimen diagnoses were compared after adjusting for preceding cytology. In a subset of preceding cytology specimens, HPV16 genotyping was considered an indicator of lesion severity. Distributions of normal and CIN1 diagnoses varied widely, with laboratories favoring either normal (5.5%-57.7%) or CIN1 diagnoses (23.3%-86.7%; P < .001 for normal:CIN1 variability). Excluding extreme values, 6.2% to 14.4% of diagnoses were CIN2 (P < .001). For CIN2 diagnoses, HPV16 positivity in the preceding cytology varied between 39.0% in the largest laboratory and 57.4% in others (P < .001), suggesting differential interpretation, not population differences, as a cause of variability. In conclusion, the frequency of diagnoses requiring special staining (p16INK4a immunostaining) to adjudicate equivocal CIN2 will be sizable and vary between laboratories, especially if extended to a fraction of CIN1 lesions. [ABSTRACT FROM AUTHOR]

Study purpose: We ascertained the follow-up care after an abnormal cytology (Papanicolaou) screening in the San Martı´n region of Peru´ and assessed the status of women who had not received adequate care. Basic procedures: We identified women with an abnormal cytology and assessed their medical records, laboratory registries, death certificates and interviewed them at home. Re-screening, diagnosis and treatment were offered. Main findings: Only 46 (25%) of the 183 women identified received appropriate follow-up care. At re-screening 31 (34%) had a normal result, 9 (10%) were diagnosed with CIN1 and 50 (56%) had CIN2 or worse. Principal conclusions: In this setting, follow-up care after an abnormal cytology was very poor and could explain the lack of impact of cervical cancer screening. Women with an abnormal cytology constitute a high-risk group that should be a priority for health services. [Copyright &y& Elsevier]

Objective: Endocervical curettage (ECC) specimens obtained during colposcopy can detect cervical cancer and precursors otherwise missed by biopsy alone, but the procedure can be painful and reduce compliance with needed follow-up. ECC is routinely performed in the Calgary Health Region colposcopy clinics, permitting a look at its real-world utility. Study Design: We analyzed pathology and colposcopy reports from 2003 to 2007. We calculated the added diagnostic utility of ECC compared with cervical biopsy alone. Results: ECC increased the diagnostic yield of cervical intraepithelial neoplasia grade 2 or worse (cervical intraepithelial neoplasia [CIN]2+) in 1.01% of 13,115 colposcopically guided biopsy examinations. Therefore, 99 ECC specimens were taken to detect 1 additional CIN2+. ECC detected 5.4% of 2443 CIN2+ subjects otherwise missed by biopsy alone. Utility was greatest among women aged 46 years or older referred after a high-grade cytology. Conclusion: ECC is rarely informative when used routinely in colposcopic practice. Older women referred after high-risk cytology benefit most from ECC. [Copyright &y& Elsevier]

Objective: To calculate pooled risk estimates for combinations of cytology result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to provide a basis for risk-stratified colposcopy and biopsy practice.Data Source: A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search was conducted on June 9, 2018, using key words such as "uterine cervical neoplasms," "cervical cancer," "mass screening," "early detection of cancer," and "colposcopy."Methods Of Study Selection: Eligible studies must have included colposcopic impression and either cytology results or HPV 16/18 partial genotype results as well as a histologic biopsy diagnosis from adult women. Manuscripts were reviewed for the following: cytology, HPV status, and colposcopy impression as well as age, number of women, and number of cervical intraepithelial neoplasia (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations of cytology, genotype, and colposcopic impression.Tabulation, Integration, and Results: Of 340 abstracts identified, nine were eligible for inclusion. Data were also obtained from three unpublished studies, two of which have since been published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns across studies in the lowest risk groups such that risk estimates were similar despite different referral populations and study designs. Women with a normal colposcopy impression (no acetowhitening), less than high-grade squamous intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of prevalent precancer. Women with at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high-grade colposcopic impression were at highest risk of prevalent precancer.Conclusion: Our results support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels. [ABSTRACT FROM AUTHOR]

Background The goal of cervical screening is to detect and treat precancers before some become cancer. We wanted to understand why, despite state-of-the-art methods, cervical cancers occured in relationship to programmatic performance at Kaiser Permanente Northern California (KPNC), where > 1,000,000 women aged ≥ 30 years have undergone cervical cancer screening by triennial HPV and cytology cotesting since 2003. Methods We reviewed clinical histories preceding cervical cancer diagnoses to assign “causes” of cancer. We calculated surrogate measures of programmatic effectiveness (precancers/(precancers and cancers)) and diagnostic yield (precancers and cancers per 1000 cotests), overall and by age at cotest (30–39, 40–49, and ≥ 50 years). Results Cancer was rare and found mainly in a localized (treatable) stage. Of 623 cervical cancers with at least one preceding or concurrent cotest, 360 (57.8%) were judged to be prevalent (diagnosed at a localized stage within one year or regional/distant stage within two years of the first cotest). Non-compliance with recommended screening and management preceded 9.0% of all cancers. False-negative cotests/sampling errors (HPV and cytology negative), false-negative histologic diagnoses, and treatment failures preceded 11.2%, 9.0%, and 4.3%, respectively, of all cancers. There was significant heterogeneity in the causes of cancer by histologic category (p < 0.001 for all; p = 0.002 excluding prevalent cases). Programmatic effectiveness (95.3%) and diagnostic yield were greater for squamous cell versus adenocarcinoma histology (p < 0.0001) and both decreased with older ages (p trend < 0.0001). Conclusions A state-of-the-art intensive screening program results in very few cervical cancers, most of which are detected early by screening. Screening may become less efficient at older ages. [ABSTRACT FROM AUTHOR]