HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management

Nature Reviews Clinical Oncology, Год журнала: 2022, Номер 19(5), С. 306 - 327

Опубликована: Фев. 1, 2022

Язык: Английский

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Detection of Occult Recurrence Using Circulating Tumor Tissue Modified Viral HPV DNA among Patients Treated for HPV-Driven Oropharyngeal Carcinoma

Clinical Cancer Research, Год журнала: 2022, Номер 28(19), С. 4292 - 4301

Опубликована: Май 16, 2022

Despite generally favorable outcomes, 15% to 25% of patients with human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) will have recurrence. Current posttreatment surveillance practices rely on physical examinations and imaging are inconsistently applied. We assessed circulating tumor tissue modified viral (TTMV)-HPV DNA obtained during routine among a large population real-world patients.This retrospective clinical case series included 1,076 consecutive across 108 U.S. sites who were ≥ 3 months for HPV-driven OPSCC had one or more TTMV-HPV tests (NavDx, Naveris Laboratories) between February 6, 2020, June 29, 2021. Test results compared subsequent evaluations.Circulating was positive in 80 (7.4%) patients, follow-up available all. At first testing, 21 (26%) known recurrence while 59 (74%) not recurrent disease. Among these 55 (93%) subsequently confirmed recurrence, 2 clinically suspicious lesions, "no evidence disease" (NED) at last follow-up. To date, the overall predictive value testing disease is 95% (N = 76/80). In addition, point-in-time negative 1,198/1,256).These findings highlight potential practice. As tool, positivity indication majority cases, pre-dating identification by exams. These data may inform future guideline-endorsed strategies malignancy surveillance. See related commentary Colevas, p. 4171.

Язык: Английский

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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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Post-treatment monitoring of surgically treated oropharyngeal squamous cell carcinoma patients using human papillomavirus cell-free DNA

Oral Oncology, Год журнала: 2025, Номер 163, С. 107225 - 107225

Опубликована: Март 5, 2025

The incidence rate of human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing. Despite good prognosis, recurrence can decrease health-related quality life and increase mortality, so post-treatment monitoring important for patient outcomes. One potential biomarker HPV cell-free DNA (cfDNA) from blood plasma. Plasma samples at start treatment during follow-up 27 OPSCC patients were analyzed cfDNA six high-risk types using a multiplex digital PCR assay. Presence was compared to tumor status determined by p16INK4a immunohistochemistry, DNA, RNA HPV16 E6 serology. At treatment, sensitivity detection in HPV-driven cases 89 % (17/19), while specificity 100 among 39 plasma 8 HPV-negative cases. A median 4 per over mean time 11 months available. Positive negative predictive values assessed on per-test-basis. testing after completion therapy had positive value HPV-OPSCC within one year, 98 %. In recurrent OPSCC, detectable between 3 6.8 before routine examination methods. Post-treatment early could be aided patients.

Язык: Английский

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Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

JAMA Oncology, Год журнала: 2019, Номер 5(7), С. 985 - 985

Опубликована: Май 2, 2019

Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence HPV-positive head and neck squamous cell carcinoma (HNSCC).To evaluate the dynamics HPV detection associations disease outcomes in patients HPV-negative HNSCC.This prospective, 2-institution, tertiary referral center study 396 newly diagnosed cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis completion primary therapy. Weekly during radiotherapy. Purified tumor sample evaluated for 37 types, viral load quantified by type-specific real-time polymerase chain reaction. Cancers stratified status, classified as type if identical that detected nontumor type.Prevalence before, during, after Associations between tumor-type nontumor-type recurrence-free overall survival evaluated.Of (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; 354 [89.4%] white race/ethnicity), 217 had cancer; 170, 9, unknown HNSCC. The prevalence higher among compared (24 194 [84.2%] vs 170 202 [12.4%]; P < .001). HPV-16 an 81% sensitivity 100% specificity HPV-16-positive decreased significantly therapy odds ratio probability infection each increasing month (0.41; 95% CI, 0.33-0.52; .001), whereas those types did not (1.01; 0.97-1.06; = .62). Current smoking a reduced clearance (hazard [HR], 0.54; 0.32-0.93). Two-year lower than without detectable (68% 95%; adjusted HR, 6.61; 1.86-23.44; .003), (55% 88%; 3.72; 1.71-8.09; No observed HNSCC.Prevalence rapidly therapy, increased risk death. Analysis has considerable promise biomarker treatment response progression.

Язык: Английский

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Optimizing Treatment De-Escalation in Head and Neck Cancer: Current and Future Perspectives

The Oncologist, Год журнала: 2020, Номер 26(1), С. 40 - 48

Опубликована: Сен. 21, 2020

Abstract Treatment of locoregionally advanced head and neck squamous cell carcinoma involves a multidisciplinary approach that combines surgery, radiotherapy, systemic therapy. These curative strategies are associated with significant acute long-term toxicities. With the emergence human papillomavirus (HPV) as an etiologic factor primarily oropharyngeal carcinoma, higher cure rates juxtaposed substantial treatment-related morbidity mortality has led to interest in de-escalated therapeutic strategies, goal optimizing oncologic outcomes while reducing toxicity. Currently explored include replacing, reducing, or omitting cytotoxic chemotherapy; dose volume radiotherapy; incorporation less-invasive surgical approaches. Potential biomarkers select patients for treatment de-escalation clinical risk stratification, adjuvant based on pathologic features, response induction therapy, molecular markers. The optimal patient selection strategy is critically important evolving locoregional cancer. Recently, two large phase III trials, RTOG 1016 De-ESCALaTE, failed de-escalate HPV-associated cancer by demonstrating inferior replacing cisplatin cetuximab combination radiation. This serves cautionary tale future design trials this population, which will need leverage toxicity efficacy endpoints. Our review summarizes completed ongoing cancer, particular emphasis trial design. Implications Practice standard multimodality underscores seek less-intensive therapies reduced symptom burden through paradigms minimize maintaining control appropriately selected patients. Controversy regarding criteria therapy multiple parallel undergoing investigation. Well-designed optimize multimodal needed. Given absence positive randomized testing date, practicing oncologists should exercise caution administer established standard-of-care outside context trial.

Язык: Английский

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Cell-Free HPV DNA Provides an Accurate and Rapid Diagnosis of HPV-Associated Head and Neck Cancer

Clinical Cancer Research, Год журнала: 2021, Номер 28(4), С. 719 - 727

Опубликована: Ноя. 29, 2021

Abstract Purpose: HPV-associated head and neck squamous cell carcinoma (HPV+HNSCC) is the most common malignancy in United States continues to increase incidence. Current diagnostic approaches for HPV+HNSCC rely on tissue biopsy followed by histomorphologic assessment detection of HPV indirectly p16 IHC. Such are invasive have variable sensitivity. Experimental Design: We conducted a prospective observational study 140 subjects (70 cases 70 controls) test hypothesis that noninvasive approach would improved accuracy, lower cost, shorter interval compared with standard approaches. Blood was collected, processed circulating tumor DNA (ctHPVDNA), analyzed custom ddPCR assays genotypes 16, 18, 33, 35, 45. Diagnostic performance, were calculated clinical workup using ctHPVDNA combined cross-sectional imaging physical examination findings. Results: Sensitivity specificity detecting 98.4% 98.6%, respectively. composite imaging/physical 95.1% accuracy this significantly higher than care (Youden index 0.937 vs. 0.707, P = 0.0006). Costs 36% 38% less median 26 days less. Conclusions: A demonstrated reduced time diagnosis could be viable alternative future.

Язык: Английский

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Early HPV ctDNA Kinetics and Imaging Biomarkers Predict Therapeutic Response in p16+ Oropharyngeal Squamous Cell Carcinoma

Clinical Cancer Research, Год журнала: 2021, Номер 28(2), С. 350 - 359

Опубликована: Окт. 26, 2021

Abstract Purpose: In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with progression after chemoradiation, (ii) compare the predictive value ctDNA imaging biomarkers MRI FDG-PET. Experimental Design: Serial blood samples were collected from patients AJCC8 stage III OPSCC (n = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, 7; posttreatment. All also had dynamic-contrast-enhanced diffusion-weighted MRI, as well FDG-PET scans pre-chemoradiation week 2 chemoradiation. values analyzed for prediction freedom (FFP), correlations aggressive subvolumes low volume (TVLBV) apparent diffusion coefficient (TVLADC), metabolic (MTV) using Cox proportional hazards model Spearman rank correlation. Results: Low pretreatment an early increase in compared baseline significantly associated superior FFP (P &lt; 0.02 P 0.05, respectively). At 4 or 7, neither counts nor clearance 0.8). Pretreatment correlated nodal TVLBV, TVLADC, MTV 0.03), while these metrics primary tumor. Multivariate analysis showed that performed comparably predict FFP. Conclusions: Early definitive may therapy response OPSCC.

Язык: Английский

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Circulating HPV DNA as a Marker for Early Detection of Relapse in Patients with Cervical Cancer

Clinical Cancer Research, Год журнала: 2021, Номер 27(21), С. 5869 - 5877

Опубликована: Июль 1, 2021

Abstract Purpose: Almost all cervical cancers are caused by human papillomavirus (HPV) and patients with advanced stage at high risk for relapse. Circulating HPV DNA (HPV ctDNA) may serve as a residual tumor marker the end of chemoradiation or to predict relapse during follow-up period. Experimental Design: We analyzed serum samples from 94 HPV16- HPV18-related CCs BioRAIDs prospective cohort. Samples were collected before after treatment an 18-month Using digital droplet PCR (ddPCR), we assessed relevance circulating E7 gene disease compared integration site PIK3CA mutations. Finally, prognostic impact was its prediction value Results: most sensitive marker, superior both sites mutations in serum. detected 63% (59/94) patients, treatment. ctDNA detection sample associated FIGO (P = 0.02) para-aortic lymph node involvement 0.01). The level positively correlated copy number (R 0.39, P &lt; 0.001). Complete clearance significantly longer PFS 0.0001). Patients persistent relapsed median time 10 months (range, 2–15) detection. Conclusions: is useful cancer. See related commentary Wentzensen Clarke, p. 5733

Язык: Английский

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Liquid BIOpsy for MiNimal RESidual DiSease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS)—a personalised circulating tumour DNA analysis in head and neck squamous cell carcinoma

British Journal of Cancer, Год журнала: 2022, Номер 126(8), С. 1186 - 1195

Опубликована: Фев. 7, 2022

Head and neck squamous cell carcinoma (HNSCC) remain a substantial burden to global health. Cell-free circulating tumour DNA (ctDNA) is an emerging biomarker but has not been studied sufficiently in HNSCC.We conducted single-centre prospective cohort study investigate ctDNA patients with p16-negative HNSCC who received curative-intent primary surgical treatment. Whole-exome sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissue. We utilised RaDaRTM, highly sensitive personalised assay using deep for tumour-specific variants, analyse serial pre- post-operative plasma samples evidence of minimal residual disease recurrence.In 17 analysed, panels were designed detect 34 52 somatic variants. Data show detection baseline taken prior surgery patients. In post-surgery samples, could be detected at levels as low 0.0006% variant allele frequency. all cases clinical recurrence date, progression, lead times ranging from 108 253 days.This illustrates the potential detecting demonstrates feasibility assays recurrence.

Язык: Английский

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