Assessment of immune biomarkers and establishing a triple negative phenotype in gynecologic cancers

Contos, G.; Baca, Yasmine; Xiu, Joanne; Brown, Jubilee; Holloway, Robert; Korn, W. Michael; Herzog, Thomas J.; Jones, Nathaniel; Winer, Ira

doi:10.1016/j.ygyno.2021.09.011

Cited by 9 publications

(9 citation statements)

References 36 publications

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“…Although vulvar cancers are often included in many of the IO “basket” studies, they are usually too few in number to draw meaningful conclusions related to vulvar cancer specifically. PD-L1 expression has been found to be highly prevalent in vulvar cancers while maintaining a low overall TMB 26 . The current study found 82.4% of all vulvar cancers, regardless of HPV status, were PD-L1 positive.…”

Section: Discussionsupporting

confidence: 43%

“…vulvar cancer specifically. PD-L1 expression has been found to be highly prevalent in vulvar cancers while maintaining a low overall TMB (26). The current study found 82.4% of all vulvar cancers, regardless of HPV status, were PD-L1 positive.…”

supporting

confidence: 43%

“…The relationship between PD-1/PD-L1 expression, TMB, and MSI is unclear (14,26,27); each has been identified as a possible independent predictor of response to IOs across many cancer types (28)(29)(30). Although vulvar cancers are often included in many of the IO "basket" studies, they are usually too few in number to draw meaningful conclusions related to…”

Section: The Genomic Landscape Of Vscmentioning

confidence: 99%

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The Genomic Landscape of Vulvar Squamous Cell Carcinoma

Corey

Wallbillich

et al. 2023

International Journal of Gynecological Pathology

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Vulvar squamous cell cancer (VSC) accounts for 90% of vulvar cancers. Next-generation sequencing studies of VSC imply human papillomavirus (HPV) and p53 status play separate roles in carcinogenesis and prognosis. We sought to describe the genomic landscape and analyze the immunologic profiles of VSC with respect to HPV and p53 status. A total of 443 VSC tumors underwent tumor profiling. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded tumor samples. PD-L1, microsatellite instability were tested by fragment analysis, IHC, and next-generation sequencing. Tumor mutational burden—high was defined as >10 mutations per MB. HPV 16/18 positive (HPV+) status was determined using whole exome sequencing on 105 samples. Three cohorts were identified from 105 samples with known HPV: HPV+, HPV−/p53wt, and HPV−/p53mt. Where HPV and p53 status were examined, TP53 mutations were exclusive of HPV+ tumors. In all, 37% of samples were HPV+. Among the 66 HPV− tumors, 52 (78.8%) were HPV−/p53mt and 14 (21.2%) were HPV−/p53wt. The HPV−/p53wt cohort had a higher rate of mutations in the PI3KCA gene (42.9% HPV−/p53wt vs 26.3% HPV+ vs. 5.8% HPV−/p53mt, q=0.028) and alterations in the PI3K/AkT/mTOR pathway (57.1% HPV−/p53wt vs. 34.2% HPV+ vs. 7.7% HPV−/p53mt, q=0.0386) than the other 2 cohorts. Ninety-eight VSC tumors with HPV16/18 information underwent transcriptomic analysis and immune deconvolution method. No differences were observed in immune profiles. The HPV−/p53wt VSC tumors had significantly higher rates of mutations in the PI3KCA gene and alterations in the PI3K/AkT/mTOR pathway, a potential target that merits further investigation in this subgroup.

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Section: Discussionsupporting

confidence: 43%

supporting

confidence: 43%

Section: The Genomic Landscape Of Vscmentioning

confidence: 99%

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The Genomic Landscape of Vulvar Squamous Cell Carcinoma

Corey

Wallbillich

et al. 2023

International Journal of Gynecological Pathology

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“…In this context, coding MSI is a mediator of dMMR tumor development ( 35 ). Gynecologic cancers such as EC and human papilloma virus-driven genital tract cancers with MSI have unique phenotypic features, such as an increased TMB and a higher number of tumor-infiltrating lymphocytes (TILs) ( 36 ). This may partly account for their superior response to ICIs.…”

Section: The Status Quo and Efficacy Prediction Of Immunotherapymentioning

confidence: 99%

Evaluation of immunotherapy efficacy in gynecologic cancer

Jiang

Wu²,

Li³

2023

Front. Immunol.

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Various immunotherapies have demonstrated remarkable success over the past few decades, and have been approved for the treatment of different cancer types. However, patient responses to immunotherapy are variable, and approximately 50% of cases are refractory to these agents. Tumor biomarker-based stratification of cases may therefore help identify subpopulations that are sensitive/resistant to immunotherapy; it may also improve prediction of response in various cancers including gynecologic cancer. These biomarkers include the tumor mutational burden, microsatellite instability, mismatch repair deficiency, T cell-inflamed gene expression profile, programmed cell death protein 1 ligand 1, tumor-infiltrating lymphocytes, and numerous other genomic alterations. Future directions in the treatment of gynecologic cancer include the utilization of these biomarkers to select ideal candidates. This review focused on recent advances in the predictive ability of molecular biomarkers in patients with gynecologic cancer who undergo immunotherapy. The most recent developments in combined immunotherapy and targeted therapy strategies and novel immune interventions against gynecologic cancers have also been discussed.

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“…The studies were published between 2016 and 2022, and the tissue samples were collected from 1994 to 2020. All studies originated from -USA 16,18,[21][22][23][24][25][26][27][28] or Europe, 17,[29][30][31][32][33][34][35] except from one worldwide multicentre study. 36 Most studies [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] reported on women with vulvar SCC and, of these, eight studies included information on HPV status either from immunohistochemical p16 staining, 21,23,35 HPV RNA analysis, 31 or both p16 and DNA or RNA analysis.…”

Section: S T U D Y C H a R A C T E R I S T I C Smentioning

confidence: 99%

PD‐L1 expression in vulvar cancer: a systematic review and meta‐analysis

Baandrup,

Sand,

Aalborg

et al. 2023

Histopathology

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Programmed cell death ligand‐1 (PD‐L1) expression in cancer may predict clinical response to immunotherapeutic treatment with PD‐1/PD‐L1 inhibitors. Within the vulvar cancer field, PD‐L1 expression has only been assessed by a few studies. We conducted a meta‐analysis to examine the prevalence of PD‐L1 positivity in vulvar cancer. PubMed, Embase, and Cochrane were searched for articles reporting on PD‐L1 expression in vulvar cancer. Study selection and data extraction were performed independently by two authors. We extracted data on PD‐L1 prevalence in vulvar cancer according to combined positive score (CPS) and tumour proportion score (TPS). Cutoff values for positivity were ≥1 or ≥10 for CPS and ≥1% and ≥5% for TPS. Random‐effects models were used to estimate pooled PD‐L1 prevalence, with 95% confidence intervals (CIs). Tests of between‐study heterogeneity were evaluated by the I2 statistics. Sources of heterogeneity were explored by subgroup analyses and meta‐regression. In total, 19 studies were included. Pooled PD‐L1 prevalence in vulvar cancer was 83.4% (95% CI: 70.8–91.3; I2 = 80.0) and 53.9% (95% CI: 37.4–69.6; I2 = 93.0) according to CPS and TPS, respectively. Based on TPS, human papillomavirus (HPV)‐associated vulvar squamous cell carcinomas (SCC) showed a lower PD‐L1 prevalence (39.9%; 95% CI: 13.3–74.2) compared with HPV‐independent SCC (62.6%; 95% CI: 33.7–84.6), but meta‐regression showed no significant variation in PD‐L1 prevalence by HPV status. PD‐L1 prevalence was similar in advanced (44.9%; 95% CI: 29.8–61.1) and localized vulvar cancer (56.7%; 95% CI: 18.9–76.7). In conclusion, PD‐L1 expression in vulvar cancer is frequent but between‐study heterogeneity was high. Based on a subgroup of heterogenous studies, we found no strong variation in PD‐L1 prevalence according to HPV status and stage.

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Assessment of immune biomarkers and establishing a triple negative phenotype in gynecologic cancers

Cited by 9 publications

References 36 publications

The Genomic Landscape of Vulvar Squamous Cell Carcinoma

The Genomic Landscape of Vulvar Squamous Cell Carcinoma

Evaluation of immunotherapy efficacy in gynecologic cancer

PD‐L1 expression in vulvar cancer: a systematic review and meta‐analysis

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