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Context.—Lower Anogenital Squamous Terminology (LAST) standardization recommended p16INK4a immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs).Objective.—To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.Design.—A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.Results.—Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall (Ptrend ≤ .001) and within each HPV risk group (Ptrend ≤ .001 except for low-risk HPV [Ptrend < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group (Ptrend < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies (P < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL+ cytology, or to be diagnosed as CIN3+ by the EP (P < .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies (P < .001).Conclusions.—p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (

In 2012, national recommendations for cervical-cancer screening of women aged 30-64 years were quinquennial human papillomavirus and cytology co-testing or triennial cytology. Data from a state-wide surveillance program in New Mexico demonstrated 65.2% (95% confidence interval [95%CI]= 64.6%% to 65.7%) of women screened in 2019 had negative co-test within the last 3 years. Percentages of women screened in 2013, 2016, and 2019 with a prior negative co-test more than 5 and up to 7 years ago were 2.6% (95% CI = 2.2% to 2.9%), 2.1% (95% CI = 1.9% to 2.2%), and 6.5% (95% CI = 6.2% to 6.8%), respectively (2-sided P trend<.001). Percentages of women screened in 2013, 2016, and 2019 with a prior negative cytology more than 5 and up to 7 years ago were 3.8% (95% CI = 3.7% to 3.9%), 9.0% (95% CI = 8.7% to 9.3%), and 14.9% (95% CI = 14.4% to 15.4%), respectively (2-sided P trend<.001). Thus, in 2019, only 12.7% (95% CI = 12.4% to 13.1%) of the 30,215 women aged 30-64 years underwent co-testing and 27.7% (95% CI = 27.1% to 28.3%) of the 18,733 underwent cytology at the recommended interval. The observed under- and over-screening could result in increases in cervical-cancer incidence and harms and costs, respectively. [ABSTRACT FROM AUTHOR]

US guidelines recommend that most women older than 65 years cease cervical screening after two consecutive negative cotests (concurrent HPV and cytology tests) in the previous 10 years, with one in the last 5 years. However, this recommendation was based on expert opinion and modeling rather than empirical data on cancer risk. We therefore estimated the 5‐year risks of cervical precancer (cervical intraepithelial neoplasia grade 3 or adenocarcinoma in situ [CIN3]) after one, two and three negative cotests among 346,760 women aged 55–64 years undergoing routine cotesting at Kaiser Permanente Northern California (2003–2015). Women with a history of excisional treatment or CIN2+ were excluded. No woman with one or more negative cotests was diagnosed with cancer during follow‐up. Five‐year risks of CIN3 after one, two, and three consecutive negative cotests were 0.034% (95% CI: 0.023%–0.046%), 0.041% (95% CI: 0.007%–0.076%) and 0.016% (95% CI: 0.000%–0.052%), respectively (ptrend < 0.001). These risks did not appreciably differ by a positive cotest result prior to the one, two or three negative cotest(s). Since CIN3 risks after one or more negative cotests were significantly below a proposed 0.12% CIN3+ risk threshold for a 5‐year screening interval, a longer screening interval in these women is justified. However, the choice of how many negative cotests provide sufficient safety against invasive cancer over a woman's remaining life represents a value judgment based on the harms versus benefits of continued screening. Ideally, this guideline should be informed by longer‐term follow‐up given that exiting is a long‐term decision. What's new? US guidelines recommend that women older than 65 years cease screening for cervical cancer following two consecutive negative cotests (HPV and cytology) in the previous ten years. However, these guidelines are based on modelling and expert opinion, rather than empirical data. In this large epidemiological study, the authors estimated the risks of cervical precancer following one, two, or three negative cotests among women aged 55‐64 years. They caution that the optimal time for women to exit screening represents a value judgment, based on the harms versus benefits of continued screening. Further data are needed. [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: 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]