Cervical cancer is the second most common type of cancer affecting women worldwide. Leukocytosis have been related with treatment failure in this pathology, associated with the induction and accumulation of myeloid derived suppressor cells (MDSC) in peripheral blood. S100A9 proved to be a useful marker to identify MDSC in whole blood from patients with cancer. In this study, we analyzed the number of leukocytes that express S100A9, dividing them according to monocytic (CD14+) or granulocytic (CD15+) myeloid populations in patients with locally advanced cervical cancer (Ptes) and compared to healthy donors (Crls). Methods: Peripheral blood samples collected from 11 Crls and 19 Ptes with cervical cancer (stage IB3-IVA) treated in our Institution between 2018 and 2020 with concurrent chemoradiotherapy (cisplatin) followed by brachytherapy. Blood samples (before treatment, before brachytherapy and post-treatment assessment) were obtained. Leukocytes from buffy coat fraction were isolated and stained for S100A9, CD14 and CD15 and then analyzed by flow cytometry. The predictive value of S100A9+ cells between Ptes and Crls was evaluated and associated with therapeutic response. Results: An increase in leukocytes, granulocytes and monocytes positives for S100A9+ were observed in peripheral blood from Ptes with cervical cancer before treatment compared to Crls. Leukocytes: mean Ptes-Crls: 67.7-48.6; p=0.0017. Granulocytes: mean Ptes-Crls: 62.5-45.9; p=0.0073. Monocytes: median Ptes-Crls: 4.62-2.58; p=0.043. We did not find significant differences in S100A9+ cells over treatment between groups. Tumor response was dichotomized as complete and insufficient response (persistence + progression), relating it to S100A9+ cells. Using a logistic regression model, we observed that the percentage of leukocytes and granulocytes S100A9+ exhibited a trend close to significance of being associated with tumor response [Leukocytes odds ratio (OR): 0.908, 95% confidence interval (CI): 0.819-1.006, p=0.06; Granulocytes OR: 0.907, 95% CI: 0.821-1.002, p=0.057]. In this way, it represents that only a 1% increase in S100A9+ leukocytes or granulocytes are associated with a 9% reduction of having a complete response. Conclusions: In our study, patients with locally advanced cervical cancer presented an increase in total leukocytes and myeloid cells that express S100A9. The relationship that seems to exist between S100A9+ leukocytes and granulocytes with tumor response may suggest that patients with high levels of these circulating cells could defined a higher risk population associated with therapeutic failure. Further analysis and a larger cohort of patients with cervical cancer will be necessary to assess the potential role of S100A9+ leukocytes and myeloid cells as predictive markers. Citation Format: Yanina Veronica Langle, Pablo Damian Cresta Morgado, Denise Belgorosky, Pablo Marenco, Pablo Menéndez, Valeria Cáceres, Andrea Aguilar, Marcela Ostojich, Laura Lay, Ana María Eiján, Eduardo Omar Sandes. Patients with cervical cancer display an increase in leukocytes and myeloid cells that express S100A9 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 362.
Background Population-based cervical cancer screening (CCS) are deemed to be more cost-effective than opportunistic screening and to reduce inequalities. Implementation in Portugal has been heterogeneous, at the regional level. In Amadora healthcare cluster (Lisbon area), implementation started in April 2018 in a pilot unit and was scaled-up. We aimed to assess population-based CCS implementation in Amadora. Methods Population-based CCS targets women aged 30-65, and utilises liquid-based cytology with partial HPV genotyping (HPV16/18 and other high-risk HPV - hrHPV). Samples positive for other hrHPV undergo a cytology. HPV16/18+ and other hrHPV+ with ≥ASCUS (atypical squamous cells of undetermined significance) are referred to colposcopy. We assessed implementation according to key indicators extracted from our information system: geographic coverage, number of tests, positive results, positive predictive value of referral (number of cervical intraepithelial neoplasia-CIN/number colposcopies). Results As of 30 August 2019, CCS were in place in 4 of the 9 units, potentially covering 20904 women (48.4% of the target population). 1797 womem performed screening within the programme. Invitation for screening is currently implemented in 1 of the 4 units. Screening results were available for 1702 women, 11,1% were HPV+. From these, 26,5% were HPV 16/18+ and 86.2% positive for other hrHPV. Among the latter, 63.2% were negative for intraepithelial lesion and 36.8% were ≥ASCUS. Overall, of these 189 women, 51.3% (n = 97) were referred for colposcopy. Colposcopy results were available for 37 women, of which 13 had a CIN. PPV of referral was 35.1% (95%confidence interval: 20.7;52.6). Conclusions Despite being a population-based screening most tests are still opportunistic. There is still a limited number of colposcopies results but the current PPV of referral is low and requires further investigation. Implementation towards a full population-based screening in Amadora should continue. Key messages Implementation of a population-based cervical cancer screening in Amadora, Portugal is underway but most screening tests are still applied in an opportunistic manner. A limited number of results is avaliable to estimate positive predictive value of referral to colposcopy. Results available indicate a value of 35.1%, which requires further investigation.
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