bims-ovdlit 2026-11-08 papers

Issue of 2026–11–08
four papers selected by
Lara Paracchini, Humanitas Research

Cancer Med. 2026 Nov;pii: e72455. [Epub ahead of print]15(11):

Assessing Potential Harms From Screening Overdiagnosis and False Positives With Multicancer Early Detection Tests.

Talía Malagón, W Alton Russell, Julia V Burnier, Kyle Dickinson, Darren Brenner.

BACKGROUND: Multicancer early detection tests could be used for cancer screening, but may lead to harms, including false positive results and overdiagnosis of indolent tumors that would not have become clinically evident during that person's lifetime. We assessed the potential for these screening harms in the context of future population-based screening with a multicancer early detection test.
METHODS: We used a microsimulation model to assess potential population-level impacts of screening at ages 50-75 years with a multicancer early detection test in Canada. We assumed high test specificity (97%-99.1%) and test sensitivity increasing with cancer stage. The model includes latent indolent cancers that would not be diagnosed within that person's lifetime but can be overdiagnosed through screen-detection. We calculated the yearly and cumulative lifetime probabilities of screening overdiagnosis and false positive test results, assuming a range of preclinical screen-detectable periods (2-5 years).
RESULTS: An estimated 2.1%-6.0% of all yearly screen-detected cancers with a multicancer screening test were predicted to be overdiagnoses across scenarios. The proportion of overdiagnosis varied by site and strongly increased with age, going from 1% at age 50 to over 10% of screen-detected cancers by age 75. The test positive predictive value ranged from 15.9% to 77.6%, meaning that there could be 0.3-5.3 false positives with no underlying cancer for every true cancer case detected by the test.
CONCLUSION: Population-level multicancer screening with a multicancer early detection test would lead to screen-related overdiagnosis; healthcare systems should consider how overdiagnoses and screening false positives may increase their follow-up capacity and caseload.

Keywords: cancer risk; cancer screening; false positives; health decision model; multicancer early detection tests; overdiagnosis; positive predictive value

DOI: https://doi.org/10.1002/cam4.72455

BMC Cancer. 2026 Aug 03. pii: 1335. [Epub ahead of print]26(1):

Fallopian tube cytology combined with p53 and PAX-8 immunocytochemistry in diagnosing ovarian carcinoma: a prospective study.

Sofia Lekka, Victoria Psomiadou, Theodoros Panoskaltsis, Eleni Tsouma, Olympia Tzaida, Helen Trihia, Abraham Pouliakis, Dimitrios Korfias, Panagiotis Giannakas, Panagiotis Vakas, Nikolaos Vlahos, George Vorgias.

OBJECTIVE: Ovarian cancer has a high mortality rate, primarily due to delayed diagnosis caused by the lack of effective diagnostic tools. Based on the tubal origin of extra-uterine high grade serous carcinomas, we aimed to evaluate the diagnostic accuracy of cytological examination of ex vivo fallopian tube brushings, alone and in combination with p53 and PAX-8 immunocytochemistry, for the identification of ovarian carcinoma, with a particular focus on high-grade serous carcinoma (HGSC).
METHODS: Our study included patients who underwent pelvic surgery for any adnexal pathology. Ex vivo, fallopian tube smears were collected using a soft brush and placed on both microscopic slides and in Thin Prep solution. The cytological samples were classified as benign, atypical or malignant, followed by immunocytochemical evaluation for p53 protein and PAX-8. The SEE-Fim protocol was used for tubal histopathological assessment.
RESULTS: Out of 103 evaluable cases, pathology identified 12 borderline tumors, 44 benign cases and 47 malignant ones, including 28 high-grade serous carcinoma cases. Cytology alone demonstrated an overall accuracy of 71.88%, while p53 showed an accuracy of 73.79% and PAX-8 an accuracy of 69.90%. After combining all three methods through logistic regression analysis, specificity increased to 83.93%, positive predictive value to 78.05%, and overall accuracy to 76.60%. Following a sub-analysis focusing on high-grade serous carcinoma, cytology reached a sensitivity of 92.86%, while p53 and PAX-8 reached 82.14% and 78.57% respectively. The combination of cytology with PAX-8 further increased sensitivity to 100%.
CONCLUSIONS: The combination of tubal cytology and immunocytochemistry could be used as a reliable diagnostic tool for extrauterine high-grade serous carcinoma. Further evaluation of a larger sample size is warranted.

Keywords: Ovarian cancer; P53; PAX8; Tubal cytology; Tubal immunocytochemistry

DOI: https://doi.org/10.1186/s12885-026-16649-0

ESMO Open. 2026 Nov 03. pii: S2059-7029(26)02556-1. [Epub ahead of print]11(11): 108611

Prognostic value of PD-L1 expression and association with HRD in high-grade serous ovarian cancer: an ancillary analysis of the PAOLA-1/ENGOT-ov25 trial (GINECO).

BACKGROUND: The prognostic significance of programmed death-ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSOC) remains uncertain, because of heterogeneity in assays, scoring systems, and assessment of tumor and immune compartments across studies. We therefore evaluated its biological and prognostic relevance using a standardized pathological approach in a large, well-annotated phase III trial cohort.
MATERIALS AND METHODS: In this ancillary retrospective biomarker analysis of PAOLA-1/ENGOT-ov25, PD-L1 was assessed by 22C3 pharmDx immunohistochemistry on whole-slide sections from 324 International Federation of Gynecology and Obstetrics stage III-IV HGSOCs. Three predefined scoring systems commonly used in PD-L1 assessment were applied: tumor proportion score (TPS ≥1%), immune cell score (IC ≥1%), and combined positive score (CPS ≥1). Associations with homologous recombination deficiency (HRD), BRCA1/2 status, and survival were examined using multivariable Cox models adjusted for major clinicopathological factors.
RESULTS: PD-L1 positivity was observed in 38.2% of tumors by TPS, 62.4% by IC, and 66.1% by CPS. Positivity did not significantly vary by sampling site or timing of tissue collection relative to chemotherapy. PD-L1 positivity was enriched in HRD-positive tumors (TPS: 42.3% versus 28.0%, P = 0.017; IC: 65.1% versus 52.0%, P = 0.030; CPS: 70.4% versus 53.0%, P = 0.003) and remained independently associated with improved overall survival in adjusted analyses [TPS: adjusted hazard ratio (aHR) 0.70 (95% confidence interval 0.49-1.00), P = 0.046; IC: aHR 0.68 (0.49-0.95), P = 0.025; CPS: aHR 0.70 (0.50-0.97), P = 0.037]. Associations with progression-free survival were not statistically significant after adjustment.
CONCLUSIONS: In advanced HGSOC, standardized whole-slide PD-L1 assessment identifies an HRD-associated PD-L1-positive immune context independently associated with improved overall survival. Immune-integrated scoring approaches capture this signal more effectively than tumor-cell-restricted assessment and provide a robust framework for future ovarian cancer studies.

Keywords: PD-L1; biomarkers; gynecological cancer (ovarian); homologous recombination deficiency; precision medicine

DOI: https://doi.org/10.1016/j.esmoop.2026.108611