PD-L1 Expression in Endometrial Serous Carcinoma and Its Prognostic Significance.

PURPOSE: Programmed death-ligand 1 (PD-L1) has been widely used as a prognostic biomarker and an immunotherapeutic target in numerous cancers, but information on the clinical significance of its expression in endometrial serous carcinoma (ESC) is largely lacking. Here, we evaluate the predictive value of PD-L1 expression in ESC. MATERIALS AND METHODS: A total of 79 cases of ESC accessioned between January 2003 and September 2015 were selected for further analysis. PD-L1 expression was evaluated in whole tissue sections of these cases by using the tumor proportion score (TPS, cut-off 1%) and combined positive score (CPS, cut-off 1) scoring methods. RESULTS: Overall, there was a heterogeneous expression of PD-L1, focal or patchy, in ESCs. PD-L1 positivity was observed in 43.0% of ESCs by TPS and 73.4% of ESCs by CPS. Kaplan-Meier survival analysis showed that patients with PD-L1-positive tumors suffered significantly worse OS and PFS, when compared with PD-L1 negative tumors (log-rank p = 0.037 and p = 0.003, respectively). In contrast, PD-L1 positivity by CPS within the ESC cases showed no statistical significance for OS and PFS (log-rank p = 0.720 and p = 0.928, respectively). Multivariate Cox analysis showed that PD-L1 positivity by TPS was significantly associated with PFS (HR = 1.921, p = 0.039) but not OS (HR = 1.229, p = 0.631). CONCLUSION: PD-L1 expression is frequently found in ESC, suggesting a potential role of the PD-1/PD-L1 pathway as a potential therapeutic target for these tumors. PD-L1 expression by TPS also serves as a negative prognostic marker in ESC and implies an unfavorable outcome.

Prevalence of genotype-specific human papillomavirus in cytology specimens and cervical biopsies, and its implication in cervical cancer risk stratification: a retrospective study of 10647 cases.

Objective: This study aimed to describe the risk stratification of squamous cell carcinoma (SCC) and its precursor lesions based on HPV E6/E7 mRNA genotyping. Methods: 10647 hrHPV+ women (mean age 40.8 years), who had concurrent cytology and follow-up biopsy results available between September 2016 and May 2020, met the inclusion criteria and were selected for immediate risk analysis. Results: In this cohort, HPV-16 or 18/45+ women had significantly higher immediate risk of cervical cancer and precancer compared with other genotypes+ women. The relative immediate risk (RIR) of ASC-H+ was 2.0 (95% CI: 1.9-2.4) and SCC was 9.4 (95% CI: 5.5-15.6) for HPV-16 or 18/45+ women when compared with women positive for other 11 genotypes. Among follow-up biopsy cases, the RIR of CIN2+ was 2.7 (95% CI: 3.0-3.7) and SCC was 10.8 (95% CI: 7.2-17.4) for HPV-16 or 18/45+ women than women positive for other genotypes. Similarly, when compared with women positive for other genotypes, the RIR of CIN2+ was 2.9 (95% CI: 2.7-4.6) and SCC was 13.8 (95% CI: 3.0-66.2) for HPV-16 or 18/45+ women with ASC-US, and RIR of CIN2+ was 3.3 (95% CI: 3.1-4.6) and SCC was 22.3 (95% CI: 2.8-176.8) for HPV-16 or 18/45+ women with NILM. Conclusions: This study supports that hrHPV mRNA genotyping can be an effective risk stratification tool to identify individual at higher risk for cervical cancer or precancer, and provides important evidences for the future modifications for current China cervical cancer screening guidelines.

Clinicopathological features and outcomes in gastric-type of HPV-independent endocervical adenocarcinomas.

BACKGROUND: We aimed to analyze the clinicopathological features and outcomes of patients with gastric-type of HPV-independent endocervical adenocarcinoma (GAS HPVI ECA), and compare them with non-GAS HPVI ECA cases. METHODS: Thirty-eight GASs [including 17 minimal deviation adenocarcinoma (MDA), 21 non-MDA GAS] and 17 non-GAS HPVI ECAs were studied. Data of clinical features, pathological characteristics, treatment, and outcomes were evaluated. RESULTS: The median age of patients with GAS and non-GAS HPVI ECA was 46 and 48 years, respectively (p = 0.93). Compared with non-GAS HPVI ECAs, GAS had more common complains of vaginal watery discharge (p = 0.04). GAS cases were also associated with higher clinical stage (p = 0.036), more common in deeper cervical stromal invasion (p = 0.002) and lymphoavascular invasion (p = 0.044). GAS was associated with worse median progression-free survival (PFS) (p = 0.02) and median overall survival (OS) (p = 0.03) over patients with non-GAS HPVI ECAs. MDA had similar clinical and pathological features and prognosis compared with non-MDA GAS. Of note, serum CA19-9 levels were significantly higher in GAS than that in non-GAS HPVI ECA cases. CONCLUSIONS: GAS cases were more likely to have high risk pathological factors and poorer PFS and OS compared with non-GAS HPVI ECAs. Serum CA19-9 may be helpful for diagnosis and screening in patients with GAS.

HPV Genotype Specific and Age Stratified Immediate Prevalence of Cervical Precancers and Cancers in Women with NILM/hrHPV+: A Single Center Retrospective Study of 26,228 Cases.

PURPOSE: To investigate the prevalence of precancers [high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS)] and cancers [squamous cell carcinoma (SCC) and adenocarcinoma (ADC)] in various high-risk human papillomavirus (hrHPV) genotypes or age groups among women with negative for intraepithelial lesion or malignancy (NILM) and hrHPV-positive pap results. MATERIALS AND METHODS: In total, 26,228 women with NILM/hrHPV+ were included in the study. Among them, 5893 had immediate follow-up biopsy results available and were selected for further prevalence analysis. RESULTS: About 7.6% and 0.7% women with NILM/hrHPV+ had HSIL and AIS, respectively. The prevalence of HSIL+ squamous lesions is significantly higher in HPV-16+ group than that in other genotype groups (p < 0.0001). The prevalence of AIS+ glandular lesions is significantly higher in HPV-18/45+ groups than women in other genotype groups (p < 0.0001). In addition, the prevalence of HSIL+ lesions was significantly higher in age 25-39 years group than that in age 40-65 years group and >65 years group (p < 0.0001). Overall, the prevalence of HSIL+ in younger women was significantly higher than that in older women when using a cutoff age of 40 years (9.3% vs 5.9%, p < 0.0001) or 50 years (8.6% vs 4.9%, p < 0.0001). No significant difference in AIS+ prevalence was found among different age groups (p = 0.611). Interestingly, the prevalence of SCC and ADC in older women (≥40 years, 0.3% and 0.3%, respectively) was significantly higher than that in younger women (<40 years, 0% and 0.07%) (p = 0.001 for SCC; p = 0.02 for ADC). CONCLUSION: The significant risk of cervical precancers and cancers still exists in women with NILM/hrHPV+, notably the older patient group had a lower risk of cervical precancer, but higher risk of cancer. Therefore, HPV genotyping can be an effective supplemental tool to cytology, and patient age also needs to be considered in the clinical management of patient.