Recommendations for Use of p16/Ki67 Dual Stain for Management of Individuals Testing Positive for Human Papillomavirus.

OBJECTIVES: The Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee developed recommendations for dual stain (DS) testing with CINtec PLUS Cytology for use of DS to triage high-risk human papillomavirus (HPV)-positive results. METHODS: Risks of cervical intraepithelial neoplasia grade 3 or worse were calculated according to DS results among individuals testing HPV-positive using data from the Kaiser Permanente Northern California cohort and the STudying Risk to Improve DisparitiES study in Mississippi. Management recommendations were based on clinical action thresholds developed for the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines. Resource usage metrics were calculated to support decision-making. Risk estimates in relation to clinical action thresholds were reviewed and used as the basis for draft recommendations. After an open comment period, recommendations were finalized and ratified through a vote by the Consensus Stakeholder Group. RESULTS: For triage of positive HPV results from screening with primary HPV testing (with or without genotyping) or with cytology cotesting, colposcopy is recommended for individuals testing DS-positive. One-year follow-up with HPV-based testing is recommended for individuals testing DS-negative, except for HPV16- and HPV18-positive results, or high-grade cytology in cotesting, where immediate colposcopy referral is recommended. Risk estimates were similar between the Kaiser Permanente Northern California and STudying Risk to Improve DisparitiES populations. In general, resource usage metrics suggest that compared with cytology, DS requires fewer colposcopies and detects cervical intraepithelial neoplasia grade 3 or worse earlier. CONCLUSIONS: Dual stain testing with CINtec PLUS Cytology is acceptable for triage of HPV-positive test results. Risk estimates are portable across different populations.

The relationship of human papillomavirus and cytology co-testing results with endometrial and ovarian cancer diagnoses.

BACKGROUND: To investigate whether routine cervical screening using human papillomavirus (HPV) and cytology co-testing effectively identifies women with endometrial (EC) or ovarian (OvC) cancer. METHODS: In 2003, Kaiser Permanente Northern California implemented triennial co-testing in women aged ≥30 years. Index screening results (n = 2,385,729) were linked to subsequent EC (n = 3434) and OvC (n = 1113) diagnoses from January 1, 2003 to December 31, 2017. EC were categorized as type 1 or 2, and, selectively, EC and OvC diagnoses were stratified on whether symptoms were present at the time of the co-test. Fractions and absolute risks of EC or OvC of each co-testing result were calculated. RESULTS: Most EC (82.18%) and OvC (88.68%) were preceded by a negative HPV and negative cytology co-test. More EC were preceded by atypical squamous cells of undetermined significance (ASC-US) or more severe (ASC-US+) cytology and negative HPV test (n = 290) (8.44% of EC) compared to a negative cytology and a positive HPV test (n = 31) (0.89% of EC) (p < 0.001). The absolute risk of any EC diagnosis following ASC-US+ and negative HPV test was 0.48%. Atypical glandular cells (AGC) cytology and a negative HPV result preceded 6.92% of any EC diagnosis, with an absolute risk of 4.02%, but preceded only 1.13% of type 2 EC cases, with an absolute risk of 0.24%, in asymptomatic women. AGC cytology and a negative HPV result preceded 1.44% of OvC, with an absolute risk of 0.28%. CONCLUSIONS: Abnormal cervical screening tests, even AGC cytology, rarely precedes and poorly predict women with EC or OvC.

Risk Estimates Supporting the 2019 ASCCP Risk-Based Management Consensus Guidelines.

The 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines for the management of cervical cancer screening abnormalities recommend 1 of 6 clinical actions (treatment, optional treatment or colposcopy/biopsy, colposcopy/biopsy, 1-year surveillance, 3-year surveillance, 5-year return to regular screening) based on the risk of cervical intraepithelial neoplasia grade 3, adenocarcinoma in situ, or cancer (CIN 3+) for the many different combinations of current and recent past screening results. This article supports the main guidelines presentation by presenting and explaining the risk estimates that supported the guidelines. METHODS: From 2003 to 2017 at Kaiser Permanente Northern California (KPNC), 1.5 million individuals aged 25 to 65 years were screened with human papillomavirus (HPV) and cytology cotesting scheduled every 3 years. We estimated immediate and 5-year risks of CIN 3+ for combinations of current test results paired with history of screening test and colposcopy/biopsy results. RESULTS: Risk tables are presented for different clinical scenarios. Examples of important results are highlighted; for example, the risk posed by most current abnormalities is greatly reduced if the prior screening round was HPV-negative. The immediate and 5-year risks of CIN 3+ used to decide clinical management are shown. CONCLUSIONS: The new risk-based guidelines present recommendations for the management of abnormal screening test and histology results; the key risk estimates supporting guidelines are presented in this article. Comprehensive risk estimates are freely available online at https://CervixCa.nlm.nih.gov/RiskTables.

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years.

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2+ Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2+ might not be necessary after a negative cotest.Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more severe diagnoses. More research is needed to determine whether such prolonged management might be unnecessary following a negative cotest for those women with an initial CIN2 but otherwise only low-grade findings. Cancer Prev Res; 11(3); 165-70. ©2018 AACR.