Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2023, Номер 149(11), С. 971 - 971

Опубликована: Июль 9, 2023

Importance There is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances assays, combining identification HPV fragment analysis (tumor tissue–modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, these newer techniques has limited small cohort studies clinical trials. Objective To establish efficacy TTMV-HPV testing OPSCC a contemporary setting. Design, Setting, Participants This retrospective observational study included who underwent between April 2020 September 2022 during course routine care. For cohort, at least 1 measurement prior initiation primary therapy were included. Patients if they had test performed after completion definitive or salvage therapy. Main Outcomes Measures Per-test performance metrics, including sensitivity, specificity, positive predictive value, negative testing. Results Of 399 analysis, 163 diagnostic (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), 290 [57-70] 237 [81.7%] male). 152 (93.3%) while 11 (6.7%) HPV-negative OPSCC. The sensitivity pretreatment was 91.5% (95% CI, 85.8%-95.4% [139 tests]), specificity 100% 71.5%-100% [11 tests]). In 591 tests conducted evaluated. A total 23 molecularly confirmed pathologic recurrences. demonstrated 88.4% 74.9%-96.1% [38 43 tests]) 99.3%-100% [548 548 detecting Positive value 90.7%-100% 38 99.1% 97.9%-99.7% 553 median (range) lead time from confirmation 47 (0-507) days. Conclusions Relevance that when evaluated setting, assay both surveillance. signifying nearly 10 among false negative. Additional research required validate assay’s and, validated, then further into implementation this standard practice guidelines will required.

Язык: Английский

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Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV⁺ Oropharyngeal Cancer

JAMA Oncology, Год журнала: 2024, Номер 10(7), С. 923 - 923

Опубликована: Июнь 6, 2024

Importance Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role curative human papillomavirus−positive oropharyngeal cancer (HPV + OPC) remains undefined. Neoadjuvant nivolumab chemotherapy followed by response-adaptive treatment HPV OPC may increase efficacy while reducing toxicity. Objective To determine the deep response rate tolerability of addition neoadjuvant to response-adapted locoregional therapy (LRT) patients with OPC. Design, Setting, Participants This phase 2 nonrandomized clinical trial conducted at a single academic center enrolled 77 locoregionally advanced from 2017 2020. Data analyses were performed February 10, 2021, January 9, 2023. Interventions Addition nab-paclitaxel carboplatin (studied first OPTIMA trial) LRT stages III IV. Main Outcomes Measures Primary outcome was plus chemotherapy, defined as proportion tumors 50% or greater shrinkage per Response Evaluation Criteria Solid Tumors 1.1. Secondary outcomes progression-free (PFS) overall (OS). Swallowing function, quality life, tissue- blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression circulating tumor HPV-DNA (ctHPV-DNA), also evaluated. Results The 73 eligible (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started chemotherapy. Deep responses observed 51 (70.8%; 95% CI, 0.59-0.81). Subsequent risk- assigned follows: group A, single-modality radiotherapy alone transoral robotic surgery (28 patients); B, intermediate-dose chemoradiotherapy 45 50 Gray (34 C, regular-dose 70 75 (10 patients). Two-year PFS OS 90.0% (95% 0.80-0.95) 91.4% 0.82-0.96), respectively. By group, 2-year for A 96.4% 96.4%, 88.0% 91.0%, Lower enteral feeding rates changes weight, well improved swallowing, among who received LRT. Pathologic complete underwent 67.0%. PD-L1 nonsignificantly higher deeper PFS, ctHPV-DNA clearance significantly associated PFS. Conclusions Relevance found that is feasible has favorable tolerability, excellent OS, functional OPC, high-risk disease. Moreover, benefit high expressors, sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful patient selection. Trial Registration ClinicalTrials.gov Identifier: NCT03107182

Язык: Английский

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Human malignancies associated with persistent HPV infection

The Oncologist, Год журнала: 2024, Номер 29(6), С. 457 - 464

Опубликована: Апрель 17, 2024

Abstract Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent associated the development cancer, often occurring several decades later. These mostly arise in 6 different anatomical regions: 5 anogenital (anus, cervix, penis, vagina, vulva) sixth oropharynx. Oncogenic HPVs promote cellular proliferation genomic instability, niche target tissue also plays an important role cancer. Cells reside transitional regions between epithelia, such as anus, oropharynx, particularly vulnerable to oncogenesis.

Язык: Английский

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Analysis of AI foundation model features decodes the histopathologic landscape of HPV-positive head and neck squamous cell carcinomas

Oral Oncology, Год журнала: 2025, Номер 163, С. 107207 - 107207

Опубликована: Март 4, 2025

Язык: Английский

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Optimizing fractionation schedules for de-escalation radiotherapy in head and neck cancers using deep reinforcement learning

Radiotherapy and Oncology, Год журнала: 2025, Номер unknown, С. 110833 - 110833

Опубликована: Март 1, 2025

Язык: Английский

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A Single-Cell Transcriptome Atlas of Epithelial Subpopulations in HPV-Positive and HPV-Negative Head and Neck Cancers

Viruses, Год журнала: 2025, Номер 17(4), С. 461 - 461

Опубликована: Март 24, 2025

Persistent infection with HPV causes nearly 5% of all cancers worldwide, including cervical and oropharyngeal cancers. Compared to HPV-negative (HPV−) head neck squamous cell carcinomas (HNSCCs), HPV-positive (HPV+) HNSCCs exhibit a significantly improved treatment response; however, established regimens were largely developed for HPV− disease. Effectively de-escalating therapy optimizing protocols minimize toxicity both HPV+ tumors has been variably successful, in part due the heterogeneity cellular subpopulations. Single-cell RNA sequencing (scRNAseq) primarily used define immune populations rather than type origin, epithelial cells. To address this, we analyzed published scRNAseq data distinguish tumor as function status. We identified transcriptome signatures, ontologies, candidate biomarkers newly subpopulations attention those that are shared or enriched HNSCCs. hypothesize distinct reprogramming versus HNSCC represent important components pro-tumor environment. These described here foundation identification new epithelial-cell-specific biomarkers, effectors, targets HNSCC.

Язык: Английский

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Deep Learning for Fully Automated Prediction of Overall Survival in Patients with Oropharyngeal Cancer Using FDG-PET Imaging

Clinical Cancer Research, Год журнала: 2021, Номер 27(14), С. 3948 - 3959

Опубликована: Май 4, 2021

Accurate prognostic stratification of patients with oropharyngeal squamous cell carcinoma (OPSCC) is crucial. We developed an objective and robust deep learning-based fully-automated tool called the DeepPET-OPSCC biomarker for predicting overall survival (OS) in OPSCC using [18F]fluorodeoxyglucose (FDG)-PET imaging.The prediction model was built tested internally on a discovery cohort (n = 268) by integrating five convolutional neural network models volumetric segmentation ten OS prognostication. Two external test cohorts were enrolled-the first based Cancer Imaging Archive (TCIA) database 353) second being clinical deployment 31)-to assess performance goodness fit.After adjustment potential confounders, found to be independent predictor both TCIA [HR 2.07; 95% confidence interval (CI), 1.31-3.28 HR 2.39; CI, 1.38-4.16; P 0.002]. The also revealed good predictive performance, c-index 0.707 (95% 0.658-0.757) cohort, 0.689 0.621-0.757) 0.787 0.675-0.899) cohort; average time taken 2 minutes calculation per exam. integrated nomogram risk factors significantly outperformed [AUC at 5 years: 0.801 0.727-0.874) vs. 0.749 0.649-0.842); 0.031] cohort.DeepPET-OPSCC achieved accurate enabled objective, unbiased, rapid assessment

Язык: Английский

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Sensitivity and Specificity of Human Papillomavirus (HPV) 16 Early Antigen Serology for HPV-Driven Oropharyngeal Cancer: A Systematic Literature Review and Meta-Analysis

Cancers, Год журнала: 2021, Номер 13(12), С. 3010 - 3010

Опубликована: Июнь 16, 2021

Antibodies against HPV16 early proteins have been shown to be promising biomarkers for the identification of HPV-driven oropharyngeal cancer (HPV-OPC) among OPC cases in multiple studies. A systematic literature search was performed identify original research articles comparing HPV antigen serology with established reference methods determine molecular tumor status. Random-effects models were used calculate summary estimates sensitivity and specificity E2, E6 E7 HPV-OPC. Subgroup analyses explore heterogeneity across studies describe variables associated test performance. We identified n = 23 meeting all eligibility criteria included these meta-analysis. showed best performance pooled 83.1% (95% confidence interval (CI) 72.5-90.2%) 94.6% CI 89.0-97.4%), respectively, while E2 serological assays highly specific (E2: 92.5% 79.1-97.6%); E7: 88.5% 77.9-94.4%)) but moderately sensitive 67.8% 58.9-75.6%); 67.0% 63.2-70.6%)). revealed increased bacterially (89.9% 84.5-93.6%)) vs. vitro expressed (55.3% 41.0-68.7%)), both high (95.2% 93.0-96.7%) 91.1% 46.6-99.2%), respectively). Pooled significantly lower utilizing DNA PCR as only method compared those using a combination any two (HPV DNA, RNA, situ hybridization (ISH), p16 immunohistochemistry (IHC)), or histopathological (ISH IHC) stand-alone marker. In conclusion, seropositivity is biomarker However, its differs between depends on methods.

Язык: Английский

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Immunotherapy in head and neck squamous cell carcinoma: An updated review

Cancer Treatment and Research Communications, Год журнала: 2022, Номер 33, С. 100649 - 100649

Опубликована: Янв. 1, 2022

Squamous cell cancer of the head and neck (HNSCC) is sixth most common associated with significant morbidity mortality. The tumor microenvironment for HNSCC a complex interplay immune cells, stromal cytokines amongst others. Immunotherapy acts as an effective antineoplastic agent by influencing this environment includes checkpoint inhibitors (ICI). ICI have been approved in frontline setting recurrent metastatic (R/M) well platinum-refractory (second line) R/M HNSCC. However, recent clinical studies highlight that response to immunotherapy varies, different ICI, combination strategies play crucial role augmenting efficacy immunotherapy. An in-depth analysis focused study contexture patients receiving remains critical. Many novel immunotherapies including CAR-T therapy, oncolytic virus vaccines are underway. Ongoing trials testing neoadjuvant adjuvant settings. Furthermore, identifying better biomarkers target population benefits from paramount importance. Pioneering optimal regimen utilizing new has recently become paradigm shift treatment landscape. Herein, we summarize development all ongoing

Язык: Английский

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Tumor-Infiltrating Lymphocytes in Head and Neck Cancer: Ready for Prime Time?

Cancers, Год журнала: 2022, Номер 14(6), С. 1558 - 1558

Опубликована: Март 18, 2022

The evaluation of tumor-infiltrating lymphocytes (TILs) has received global attention as a promising prognostic cancer biomarker that can aid in clinical decision making. Proof their significance was first shown breast cancer, where TILs are now recommended the classification tumors. Emerging evidence indicates extends to other types, including head and neck cancer. In era immunotherapy treatment choice for assessment immune checkpoints is high relevance. availability standardized method from International Immuno-oncology Biomarker Working Group (IIBWG) an important cornerstone toward assessment. aim current article summarize accumulated establish clear premise future research implementation personalized management squamous cell carcinoma patients.

Язык: Английский

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