近年来，子宫颈癌的筛查策略发生了一些变化，高危型人乳头瘤病毒检测被推荐为宫颈癌的初筛方法，但初筛阳性女性的管理仍存在一定的不足，宫颈p16/Ki-67免疫细胞化学双染技术有助于进一步的分流。为了更好地指导及规范双染技术的应用，中华医学会病理学分会细胞病理学组组织相关专家特制定本共识，对p16/Ki-67双染技术的制片、判读、临床应用等进行规范，以更好地用于指导宫颈癌的筛查及管理。.

Gliomas with IDH1/2 mutations without 1p19q codeletion have been identified as the distinct diagnostic entity of IDH mutant astrocytoma (IDHmut astrocytoma). Homozygous deletion of Cyclin-dependent kinase 4 inhibitor A/B (CDKN2A/B) has recently been incorporated in the grading of these tumors. The question of whether histologic parameters still contribute to prognostic information on top of the molecular classification, remains unanswered. Here we evaluated consensus histologic parameters for providing additional prognostic value in IDHmut astrocytomas.
An international panel of seven neuropathologists scored 13 well-defined histologic features in virtual microscopy images of 192 IDHmut astrocytomas from EORTC trial 22033-26033 (low-grade gliomas) and 263 from EORTC 26053 (CATNON) (1p19q non-codeleted anaplastic glioma). For 192 gliomas the CDKN2A/B status was known. Consensus (agreement ≥ 4/7 panelists) histologic features were tested together with homozygous deletion (HD) of CDKN2A/B for independent prognostic power.
Among consensus histologic parameters, the mitotic count (cut-off of 2 mitoses per 10 high power fields standardized to a field diameter of 0.55 mm and an area of 0.24 mm2) significantly influences PFS (P = .0098) and marginally the OS (P = .07). Mitotic count also significantly affects the PFS of tumors with HD CDKN2A/B, but not the OS, possibly due to limited follow-up data.
The mitotic index (cut-off 2 per 10 40× HPF) is of prognostic significance in IDHmut astrocytomas without HD CDKN2A/B. Therefore, the mitotic index may direct the therapeutic approach for patients with IDHmut astrocytomas with native CDKN2A/B status.

The Czech Head and Neck Cancer Cooperative Group (CHNCCG) held a meeting in Tabor on 11-12 October 2019 with the aim of reaching an interdisciplinary consensus on some controversial points where international unity is absent. The meeting resulted in recommendations on resection margin size terminology (definition of terms: negative margin, close margin and positive margin) and on the adoption of terminology for neck dissections reporting according to the International Recommendation of the International Head and Neck Scientific Group and on assessment of HPV/p16 status in head and neck tumors.

OBJECTIVE: to provide accurate information about the global prevalence of human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC).
METHODS: a systematic review was performed using three main electronic databases. Studies were independently assessed by two reviewers based on established eligibility criteria, to identify the prevalence of HPV-driven OPSCC following criteria defined by the American Society of Clinical Oncology. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Statistical software MedCalc was used to perform meta-analyses.
RESULTS: from 2215 records found, 15 were included, reporting data from 6009 patients (time period range: 1980-2016), distributed in 11 countries. Eleven studies were considered as presenting low risk, and four as moderate risk of bias. Using proportion meta-analysis, pooled prevalence of HPV-driven OPSCC was 44.8 % (95 %CI: 36.4-53.5 %; i2 = 97.6 %), with the highest rates in New Zealand (74.5 %; 95 %CI: 60.9-85.3 %), and the lowest in Brazil (11.1 %; 95 %CI: 4.5-21.5 %). HPV prevalence was similar between males (45.7 %; 95 %CI: 36.5-55.0 %; i2 = 96.4 %) and females (42.2 %; 95 %CI: 34.3-50.5 %; i2 = 85.4 %). Mean/median age ranged from 59.1-67.1 years in the HPV-negative group, and from 55.7-63.5 years in the HPV-positive group. There was an overall discordance between testing by p16 (49.4 %; 95 %CI, 38.2-60.5 %; i2 = 96.2 %) and p16+ISH/PCR (44.7 %; 95 %CI, 33.5-56.2 %; i2 = 96.4 %).
CONCLUSIONS: Overall pooled prevalence of HPV-driven OPSCC was approximately 45 %, with similar distribution among males and females. Double p16/HPV-DNA/RNA testing may be considered to increase specificity and prognostic accuracy.

Of the numerous aspects involved in the diagnosis, treatment, and follow-up of cervical uterine precursor lesions, epidemiology, virology, cytology, human papillomavirus (HPV) testing, and diagnostic algorithms for equivocal and HPV-positive findings are important for pathologists. Cytology will continue to be used as a preventive medical check-up in young women, while HPV-based screening is suggested for older women. HPV screening has yielded a significant reduction in cancer precursors and invasive cervical carcinoma in numerous studies. In contrast to the sensitivity, the specificity of the HPV test is inferior to that of cytology and the morphological biomarker p16/Ki-67, so that they are suitable as methods in the triage of HPV-positive findings. Cytological abnormalities and mildly dysplastic changes could be further clarified by an HPV test or the p16/Ki-67 test. The HPV test should also be used in the follow-up of patients after conization.

BACKGROUND: BRCA1 and RASSF1A promoter methylation has been reported to be correlated with a worse survival in patients with breast cancer. However, the prognostic values of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer remain to be determined. Here, we performed this study to evaluate the prognostic significance of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer.
METHODS: A range of online databases was systematically searched to identify available studies based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. The pooled hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were applied to estimate the prognostic effect of GSTP1, p16, ESR1, and PITX2 promoter methylation in breast cancer for multivariate regression analysis.
RESULTS: 13 eligible articles involving 3915 patients with breast cancer were analyzed in this meta-analysis. In a large patient population, GSTP1 showed a trend toward a worse prognosis in overall survival (OS) (HR = 1.64, 95% CI = 0.93-2.87, P = .085). PITX2 promoter methylation was significantly correlated with a worse prognosis in OS (HR = 1.57, 95% CI = 1.15-2.14, P = .004), but no association between p16 promoter methylation and OS (HR = 0.92, 95% CI = 0.31-2.71, P = .884). PITX2 promoter methylation was significantly correlated with an unfavorable prognosis of patients with breast cancer in metastasis-free survival (MFS) (HR = 1.73, 95% CI = 1.33-2.26, P < .001). The result from 3 studies with 227 cases showed that ESR1 promoter methylation was linked to a worse prognosis in OS (HR = 1.55, 95% CI = 1.06-2.28, P = .025).
CONCLUSIONS: Our findings suggest ESR1 and PITX2 promoter methylation may be correlated with a worse survival of patients with breast cancer (ESR1: OS, PITX2: OS and MFS). The clinical utility of aberrantly methylated ESR1 and PITX2 could be a promising factor for the prognosis of breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for patients with high-grade osteosarcoma has highly improved the clinical survival. However, the prognostic and predictive role of P16 expression after neoadjuvant chemotherapy remains unclear. We first determined whether P16 expression can become a potential prognostic and predictive biomarker in high-grade osteosarcoma.
METHODS: This meta-analysis was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence intervals (95% CIs) were calculated in this analysis.
RESULTS: Four studies involving a total of 527 patients with high-grade osteosarcoma receiving neoadjuvant chemotherapy were identified. We did not find that P16 expression was correlated with sex status, histologic subtype, and tumor site (P > .1). P16 expression was found to be significantly associated with a \"good\" response to neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was observed between p16 expression and pathologic complete response after neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The expression of the P16 was not associated with clinical outcomes in overall survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P = .448; DFS: P = .263).
CONCLUSIONS: The use of P16 expression could become a promising predictive biomarker of the response to neoadjuvant chemotherapy in the white population with high-grade osteosarcoma. However, it was not correlated with the prognosis of patients in OS and DFS. More clinical researches are very essential in Asians in the future.

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OBJECTIVE: To determine the impact of implementing p16 Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions (LAST) guidelines, we compared p16 use and follow-up data before and after implementation of the guidelines.
METHODS: We reviewed all cervical biopsy specimens diagnosed by two pathologists before and after implementation of the LAST guidelines and calculated the rate of and reason for p16 use across all biopsy specimens, high-grade squamous intraepithelial lesion (HSIL) detection, and follow-up.
RESULTS: In total, 1,829 and 1,623 cervical biopsy specimens were reviewed in periods A and B, respectively. Overall p16 use increased from 2.8% to 6.2% (P < .001). Recommendations 2 and 4 increased from 0.16% and 0% of all cervical biopsy specimens in period A to 1.4% and 1.9% in period B, respectively (P < .0001). p16+ HSIL increased from 1.4% to 2.3% (P < .05). The positive predictive value of p16+ HSIL increased from 48% to 76% (P < .05).
CONCLUSIONS: Implementation of the p16 LAST guidelines resulted in a significant increase in p16 use and a significant increase in the positive predictive value of p16+ HSIL.

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