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The Prognostic Values of HPV Genotypes and Tumor PD-L1 Expression in Patients With HPV-associated Endocervical Adenocarcinoma

Authors: Zhou, Feng; Chen, Hao; Li, Meiping; Strickland, Amanda L.; Zheng, Wenxin; Zhang, Xiaofei;

The Prognostic Values of HPV Genotypes and Tumor PD-L1 Expression in Patients With HPV-associated Endocervical Adenocarcinoma

Abstract

Despite the well-established pathogenic effect of high-risk human papillomavirus (hrHPV) genotypes on endocervical adenocarcinomas (ECAs), the prognostic values of hrHPV genotypes and their association with other prognostic variables have not been established. We categorized 120 usual-type human papillomavirus–associated (HPVA) ECA cases into 3 species groups (HPV16+, HPV18/45+, and other genotypes+) based on the hrHPV status. The clinical-stage, invasion patterns (Silva), and programmed death ligand-1 (PD-L1) expression were compared among genotype groups. In addition, log-rank test and Kaplan-Meier survival curves were used to compare progression-free survival (PFS) among different patient groups. A total of 120 ECA cases with positive hrHPV tests were included in this study. Among them, 51 (42.5%) were positive for HPV16, 50 (41.7%) were positive for HPV18 or 18/45, 9 (7.5%) were positive for other hrHPV genotypes (not including HPV16/18/45). Our data showed patients had no significant difference in clinical stages (P=0.51), invasion patterns (P=0.55), and PFS (P=0.59) across genotype groups. Overall, a relatively high prevalence of PD-L1 expression was observed in HPVA ECAs (25% by tumor proportion score [TPS] and 55% by a combined positive score [CPS]). Using TPS, 19.6% (10/51) HPV16+ cases, 32.0% (16/50) cases of HPV18 or 18/45+ cases, and 22.2% (2/9) cases of other genotypes+ cases demonstrated PD-L1 positivity. No significant difference in PD-L1 expression was seen across genotype groups (P=0.35). PD-L1 expression in tumors with patterns B and C was significantly higher than in those with pattern A (P=0.00002). Patients with PD-L1-positive tumors by either CPS or TPS showed significantly poorer PFS than those with PD-L1-negative tumors (CPS, P=0.025; TPS, P=0.001). Our data support that HPV genotypes have no prognostic value in HPVA ECAs, while PD-L1 expression serves as a negative prognostic marker in HPVA ECAs and implies an unfavorable outcome.

Keywords

Adult, Human papillomavirus 16, Genotype, Human papillomavirus 18, Papillomavirus Infections, Uterine Cervical Neoplasms, Original Articles, Adenocarcinoma, Middle Aged, Prognosis, B7-H1 Antigen, Biomarkers, Tumor, Humans, Female, Aged, Follow-Up Studies

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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
8
Top 10%
Average
Top 10%
Green
hybrid