2024
De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy
Yarbrough W, Schrank T, Burtness B, Issaeva N. De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy. Viruses 2024, 16: 536. PMID: 38675879, PMCID: PMC11053602, DOI: 10.3390/v16040536.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorHead and Neck NeoplasmsHumansNeoplasm Recurrence, LocalPapillomaviridaePapillomavirus InfectionsPrecision MedicineSquamous Cell Carcinoma of Head and NeckConceptsHPV+ HNSCCHPV-associated head and neck cancerHead and neck cancerHuman papillomavirus-associatedDe-escalation therapyDetect recurrent diseaseTreatment of recurrenceHPV-associated cancersHead and neckEarly treatment of recurrencePapillomavirus-associatedDevelopment of biomarkersResponsive tumorsRecurrent diseaseStandard therapyCompanion biomarkersHPV carcinogenesisHPV vaccinationNeck cancerPoor prognosisDecrease morbidityHNSCCEarly treatmentMolecular vulnerabilitiesPersonalized therapy
2023
Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review
Lozar T, Wang W, Gavrielatou N, Christensen L, Lambert P, Harari P, Rimm D, Burtness B, Kuhar C, Carchman E. Emerging Prognostic and Predictive Significance of Stress Keratin 17 in HPV-Associated and Non HPV-Associated Human Cancers: A Scoping Review. Viruses 2023, 15: 2320. PMID: 38140561, PMCID: PMC10748233, DOI: 10.3390/v15122320.Peer-Reviewed Original ResearchConceptsSquamous cell carcinomaTriple-negative breast cancerCancer typesPredictive significancePrognostic factorsClinical outcomesPrognostic significanceCell carcinomaHuman cancersCervical squamous cell carcinomaNeck squamous cell carcinomaAvailable clinical evidenceCochrane Central RegisterInferior clinical outcomesPositive prognostic factorNegative predictive factorNegative prognostic factorWeb of ScienceCentral RegisterControlled TrialsCervical cancerClinical evidencePredictive factorsPancreatic cancerEligible studiesNoncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors
Schrank T, Kothari A, Weir W, Stepp W, Rehmani H, Liu X, Wang X, Sewell A, Li X, Tasoulas J, Kim S, Yarbrough G, Xie Y, Flamand Y, Marur S, Hayward M, Wu D, Burtness B, Anderson K, Baldwin A, Yarbrough W, Issaeva N. Noncanonical HPV carcinogenesis drives radiosensitization of head and neck tumors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2216532120. PMID: 37523561, PMCID: PMC10410762, DOI: 10.1073/pnas.2216532120.Peer-Reviewed Original ResearchConceptsNF-κB-related genesEstrogen receptor alpha expressionDeintensification of therapyTreatment-related morbidityTumor-infiltrating CD4Receptor alpha expressionHPV carcinogenesisRadiosensitization of headOncogenic subtypesPIK3CA alterationsHNSCC tumorsPatient outcomesNeck tumorsT cellsTreatment responseHNSCC cellsTherapeutic intensityAtypical featuresIndependent cohortAlpha expressionNF-κBActive tumorTNF receptorTumorsPatient dataScreening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial
Kann B, Likitlersuang J, Bontempi D, Ye Z, Aneja S, Bakst R, Kelly H, Juliano A, Payabvash S, Guenette J, Uppaluri R, Margalit D, Schoenfeld J, Tishler R, Haddad R, Aerts H, Garcia J, Flamand Y, Subramaniam R, Burtness B, Ferris R. Screening for extranodal extension in HPV-associated oropharyngeal carcinoma: evaluation of a CT-based deep learning algorithm in patient data from a multicentre, randomised de-escalation trial. The Lancet Digital Health 2023, 5: e360-e369. PMID: 37087370, PMCID: PMC10245380, DOI: 10.1016/s2589-7500(23)00046-8.Peer-Reviewed Original ResearchConceptsExtranodal extensionOropharyngeal carcinomaShort-axis diameterChallenging cohortPathology reportsECOG-ACRIN Cancer Research GroupDe-escalation trialsCancer Research GroupDe-escalation strategiesSurgical pathology reportsNational Cancer InstituteInter-reader agreementLargest short-axis diameterPostoperative chemoradiationProtocol exclusionsConcurrent chemoradiationPrimary endpointMulticentre trialPretreatment CTAdjuvant strategiesHuman papillomavirusTreatment selection toolUS National InstitutesPretreatment identificationStudy protocol
2022
Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma
Rodriguez CP, Kang H, Geiger JL, Burtness B, Chung CH, Pickering CR, Fakhry C, Le QT, Yom SS, Galloway TJ, Golemis E, Li A, Shoop J, Wong S, Mehra R, Skinner H, Saba NF, Flores ER, Myers JN, Ford JM, Karchin R, Ferris RL, Kunos C, Lynn JM, Malik S. Clinical Trial Development in TP53-Mutated Locally Advanced and Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma. Journal Of The National Cancer Institute 2022, 114: 1619-1627. PMID: 36053203, PMCID: PMC9745425, DOI: 10.1093/jnci/djac163.Peer-Reviewed Original ResearchMeSH KeywordsGenes, p53Head and Neck NeoplasmsHumansMutationPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckTumor Suppressor Protein p53ConceptsNeck squamous cell carcinomaSquamous cell carcinomaClinical trialsCell carcinomaTrial designTP53 mutationsNational Clinical Trials NetworkMetastatic disease settingsClinical trial developmentClinical Trials NetworkNovel therapeutic approachesNational Cancer InstituteMetastatic headTP53-mutated tumorsWorse outcomesClinical studiesFrequent genetic eventTherapeutic approachesCancer InstituteTrial developmentBreakout groupsPatientsDisease settingsBiomarker integrationTrials NetworkCurrent Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges.
Wise-Draper TM, Bahig H, Tonneau M, Karivedu V, Burtness B. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. American Society Of Clinical Oncology Educational Book 2022, 42: 1-14. PMID: 35486888, DOI: 10.1200/edbk_350442.Peer-Reviewed Original ResearchMeSH KeywordsB7-H1 AntigenHead and Neck NeoplasmsHumansPapillomavirus InfectionsRetrospective StudiesSquamous Cell Carcinoma of Head and NeckConceptsNeck squamous cell carcinomaSquamous cell carcinomaMetastatic headCell carcinomaSystemic therapyFirst-line systemic therapyFirst-line immunotherapyInclusion of chemotherapyImmune checkpoint blockadeNew systemic therapiesNumber of patientsAggressive local managementCombination immunotherapyLocoregional therapyOligometastatic diseaseCheckpoint blockadeNovel immunotherapiesPD-L1Lung metastasesRetrospective studyBiomarker subgroupsCurrent therapiesNeck cancerAblative approachesAntiangiogenic agents
2021
Treatment De-intensification for HPV-Positive Oropharynx Cancer: What Is Currently Acceptable?
Cmelak AJ, Ferris RL, Chen AM, Seiwert T, Burtness B. Treatment De-intensification for HPV-Positive Oropharynx Cancer: What Is Currently Acceptable? Journal Of Clinical Oncology 2021, 39: 2732-2733. PMID: 34043410, DOI: 10.1200/jco.21.00594.Peer-Reviewed Original ResearchHypoxia-Guided Therapy for Human Papillomavirus-Associated Oropharynx Cancer
Burtness B, Contessa J. Hypoxia-Guided Therapy for Human Papillomavirus-Associated Oropharynx Cancer. Journal Of The National Cancer Institute 2021, 113: 652-653. PMID: 33429429, PMCID: PMC8168139, DOI: 10.1093/jnci/djaa187.Peer-Reviewed Original Research
2020
Head and neck squamous cell carcinoma
Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nature Reviews Disease Primers 2020, 6: 92. PMID: 33243986, PMCID: PMC7944998, DOI: 10.1038/s41572-020-00224-3.Peer-Reviewed Original ResearchMeSH KeywordsHuman papillomavirus 16HumansPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckTobacco UseConceptsNeck squamous cell carcinomaSquamous cell carcinomaHuman papillomavirusCell carcinomaOral cavityLarynx cancerAJCC/UICC staging systemEGFR monoclonal antibody cetuximabLate stage HNSCCLeast toxic therapyImmune checkpoint inhibitorsHPV-positive HNSCCTreatment of recurrentHPV-positive diseaseOral cavity cancerUICC staging systemHPV-negative HNSCCPre-malignant lesionsDegree of dysplasiaMonoclonal antibody cetuximabUnresectable diseaseCheckpoint inhibitorsPrimary chemoradiotherapyCytotoxic chemotherapyMost patients
2019
Point/Counterpoint: Do We De-escalate Treatment of HPV-Associated Oropharynx Cancer Now? And How?
Wirth LJ, Burtness B, Nathan CO, Grégoire V, Richmon J. Point/Counterpoint: Do We De-escalate Treatment of HPV-Associated Oropharynx Cancer Now? And How? American Society Of Clinical Oncology Educational Book 2019, 39: 364-372. PMID: 31099643, DOI: 10.1200/edbk_238315.Peer-Reviewed Original ResearchConceptsDe-escalate treatmentOropharyngeal carcinomaHPV-positive oropharyngeal carcinomaNeck cancer clinical researchNew systemic agentsPhase II trialPhase III trialsTreatment-related morbidityHigh cure ratesCancer clinical researchConcurrent cisplatinII trialOropharynx cancerPrimary surgeryDose intensityIII trialsInstitutional seriesInvasive resectionMultimodality treatmentSystemic agentsSystemic therapyPrimary diseaseCure rateToxic therapiesMultimodality strategy
2018
Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. The Lancet 2018, 393: 40-50. PMID: 30449625, PMCID: PMC6541928, DOI: 10.1016/s0140-6736(18)32779-x.Peer-Reviewed Original ResearchConceptsHPV-positive oropharyngeal carcinomaProgression-free survivalOverall survivalNon-inferiority trialCisplatin groupCetuximab groupOropharyngeal carcinomaSevere toxicityEligibility criteriaPositive oropharyngeal squamous cell carcinomaHuman papillomavirus-positive oropharyngeal cancerNational Cancer Institute-USAZubrod performance status 0Oropharyngeal squamous cell carcinomaAdequate bone marrowPerformance status 0Replacement of cisplatinZubrod performance statusInferior overall survivalTobacco smoking historyAmerican Joint CommitteeNon-inferiority criteriaSquamous cell carcinomaStandard of careNon-inferiority marginHPV status in unknown primary head and neck cancer: Prognosis and treatment outcomes
Cheraghlou S, Torabi SJ, Husain ZA, Otremba MD, Osborn HA, Mehra S, Yarbrough WG, Burtness BA, Judson BL. HPV status in unknown primary head and neck cancer: Prognosis and treatment outcomes. The Laryngoscope 2018, 129: 684-691. PMID: 30151832, DOI: 10.1002/lary.27475.Peer-Reviewed Original ResearchMeSH KeywordsAgedFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedNeoplasms, Unknown PrimaryPapillomavirus InfectionsPrognosisRetrospective StudiesTreatment OutcomeConceptsHPV-negative patientsTreatment deintensificationCN3 diseaseHPV statusNeck cancerUnivariate Kaplan-Meier analysisTumor human papillomavirus (HPV) statusCox survival regressionHPV-negative diseaseIdentifiable primary tumorUnknown primary headHPV-positive patientsHuman papillomavirus (HPV) statusTumor HPV statusKaplan-Meier analysisTreatment-related outcomesSignificant prognostic valuePoor patient survivalCases of headDefinitive chemoradiotherapyDefinitive radiotherapyMetastatic nodesNodal classificationUnknown primaryTherapeutic challengePatterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma
Lee NCJ, Kelly JR, Park HS, An Y, Judson BL, Burtness BA, Husain ZA. Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma. Oral Oncology 2018, 85: 35-39. PMID: 30220317, DOI: 10.1016/j.oraloncology.2018.08.001.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBrachytherapyCarcinoma, Squamous CellCombined Modality TherapyFemaleFollow-Up StudiesHumansLymphatic MetastasisMaleMiddle AgedNeck DissectionNeoplasm MetastasisNeoplasm Recurrence, LocalOropharyngeal NeoplasmsPapillomavirus InfectionsProgression-Free SurvivalProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSalvage TherapyConceptsProgression-free survivalInvolved lymph nodesDistant metastasisPatterns of failureLocoregional recurrenceLymph nodesHuman papillomavirus-positive oropharyngeal carcinomaMultivariate analysisEdition American Joint CommitteeRate of DMWorse progression-free survivalHigh DM rateDedicated clinical trialsAmerican Joint CommitteeCancer (AJCC) staging systemProportional hazards regressionExternal beam radiationOropharynx cancerFree survivalNeck dissectionOropharyngeal carcinomaOverall survivalDisease recurrenceIntraoperative brachytherapyOPC patients
2017
Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer
Biktasova A, Hajek M, Sewell A, Gary C, Bellinger G, Deshpande HA, Bhatia A, Burtness B, Judson B, Mehra S, Yarbrough WG, Issaeva N. Demethylation Therapy as a Targeted Treatment for Human Papillomavirus–Associated Head and Neck Cancer. Clinical Cancer Research 2017, 23: 7276-7287. PMID: 28916527, DOI: 10.1158/1078-0432.ccr-17-1438.Peer-Reviewed Original ResearchConceptsClinical trialsHNSCC cellsMatrix metalloproteinasesHuman papillomavirus-associated headNeck squamous cell carcinomaSquamous cell carcinomaAbility of HPVClin Cancer ResTumor cell proliferationNeck cancer cellsWindow trialsCell carcinomaEffective therapyPreclinical modelsHPVHPV oncogenesMouse modelMouse blood vesselsDNA demethylating agentHNSCCXenografted tumorsHPV genesIFN responseTherapyTumor samplesThe prognostic value of extranodal extension in human papillomavirus‐associated oropharyngeal squamous cell carcinoma
An Y, Park HS, Kelly JR, Stahl JM, Yarbrough WG, Burtness BA, Contessa JN, Decker RH, Koshy M, Husain ZA. The prognostic value of extranodal extension in human papillomavirus‐associated oropharyngeal squamous cell carcinoma. Cancer 2017, 123: 2762-2772. PMID: 28323338, DOI: 10.1002/cncr.30598.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellChemoradiotherapy, AdjuvantFemaleHead and Neck NeoplasmsHumansMaleMiddle AgedMultivariate AnalysisNeoplasm InvasivenessNeoplasm StagingOropharyngeal NeoplasmsOtorhinolaryngologic Surgical ProceduresPapillomaviridaePapillomavirus InfectionsPrognosisPropensity ScoreProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesSquamous Cell Carcinoma of Head and NeckSurvival RateConceptsOropharyngeal squamous cell carcinomaENE-positive patientsHPV-positive oropharyngeal squamous cell carcinomaExtranodal extensionHPV-positive patientsOverall survivalPrimary surgeryPT4 tumorsAdjuvant chemoradiationConcurrent chemoradiotherapyAdjuvant treatmentPositive oropharyngeal squamous cell carcinomaPT3/pT4 tumorsMultivariable Cox regression analysisNational Cancer Data BasePredictors of OSPropensity score-matched comparisonAdjuvant concurrent chemoradiotherapyCharlson-Deyo scoreInvolved lymph nodesAdverse prognostic factorInferior overall survivalLymph node statusCox regression analysisSingle-institution studyTRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma
Hajek M, Sewell A, Kaech S, Burtness B, Yarbrough WG, Issaeva N. TRAF3/CYLD mutations identify a distinct subset of human papillomavirus‐associated head and neck squamous cell carcinoma. Cancer 2017, 123: 1778-1790. PMID: 28295222, PMCID: PMC5419871, DOI: 10.1002/cncr.30570.Peer-Reviewed Original ResearchConceptsHPV-positive HNSCCNeck squamous cell carcinomaDe-escalation therapyHPV-positive HNSCCsMechanisms of HPVRecurrent metastatic diseaseBetter overall survivalSquamous cell carcinomaNuclear factor-κB signalingFactor-κB signalingNew therapeutic strategiesNuclear factor κBHPV vaccineCancer Genome AtlasCurative optionHPV statusMetastatic diseaseOverall survivalCervical cancerPatient survivalSmoking characteristicsCell carcinomaHuman papillomavirusLifelong morbidityClinical trialsA Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma
Husain ZA, Chen T, Corso CD, Wang Z, Park H, Judson B, Yarbrough W, Deshpande H, Mehra S, Kuo P, Decker RH, Burtness BA. A Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus–Related Oropharyngeal Squamous Cell Carcinoma. JAMA Oncology 2017, 3: 358-365. PMID: 27737449, DOI: 10.1001/jamaoncol.2016.4581.Peer-Reviewed Original ResearchConceptsOropharyngeal squamous cell cancerAJCC/UICC systemStaging systemStage IAStage IBHuman papillomavirusPrognostic abilityUICC systemAJCC/UICC staging systemStage IICurrent American Joint CommitteeOropharyngeal squamous cell carcinomaInternational Cancer Control (UICC) staging systemOropharyngeal cancer NetworkNational Cancer DatabasePrimary radiation therapyOverall survival rateAmerican Joint CommitteeCancer/UnionEdition staging systemKaplan-Meier methodSquamous cell cancerNovel staging systemSquamous cell carcinomaLog-rank testHuman Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck Squamous Cell Carcinoma
Psyrri A, Rampias T, Burtness B. Human Papillomavirus Genotypes Conferring Poor Prognosis in Head and Neck Squamous Cell Carcinoma. JAMA Oncology 2017, 3: 125. PMID: 27607105, DOI: 10.1001/jamaoncol.2016.3409.Peer-Reviewed Original Research
2016
E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group
Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group. Journal Of Clinical Oncology 2016, 35: 490-497. PMID: 28029303, PMCID: PMC5455313, DOI: 10.1200/jco.2016.68.3300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Administration ScheduleExanthemaFemaleHuman papillomavirus 16HumansInduction ChemotherapyMaleMiddle AgedNeutropeniaOropharyngeal NeoplasmsPapillomavirus InfectionsRadiotherapy DosageRemission InductionConceptsOropharyngeal squamous cell carcinomaComplete clinical responseCycle of ICPhase II trialProgression-free survivalSquamous cell carcinomaWeekly cetuximabII trialCell carcinomaPack-year smoking historyResectable squamous cell carcinomaFavorable-risk patientsPrimary end pointOverall survival rateHigh cure ratesCancer Research GroupGy of radiationRadiation doseLong-term toxicityRadiation dose reductionChemoradiation resultsICS respondersInduction chemotherapyLate sequelaeClinical responseTreatment de-intensification strategies for head and neck cancer
Kelly JR, Husain ZA, Burtness B. Treatment de-intensification strategies for head and neck cancer. European Journal Of Cancer 2016, 68: 125-133. PMID: 27755996, PMCID: PMC5734050, DOI: 10.1016/j.ejca.2016.09.006.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Squamous CellChemoradiotherapyCombined Modality TherapyHead and Neck NeoplasmsHumansMinimally Invasive Surgical ProceduresOropharyngeal NeoplasmsOtorhinolaryngologic Surgical ProceduresPapillomavirus InfectionsRadiotherapy DosageRadiotherapy, AdjuvantSquamous Cell Carcinoma of Head and NeckConceptsHigh-risk human papillomavirus infectionHuman papillomavirus infectionLong-term morbiditySquamous cell cancerSquamous cell carcinomaDe-intensification strategiesIntensive treatment regimensAltered fractionation schemesDefinitive chemoradiationAdjuvant radiationPapillomavirus infectionCell cancerImpairs qualityTreatment regimensCell carcinomaNeck cancerRecent trialsSimilar efficacySuch cancersInvasive surgeryTreatment intensityCancerRadiation dosePreliminary dataSurgery