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Current state of play for HPV-positive oropharyngeal cancers

      Highlights

      • Carcinomas of the oropharynx have increased in incidence with a rise in HPV16 infections.
      • Standard treatment for patients with oropharyngeal cancers does not differ based on HPV status.
      • An adequate de-escalation strategy has yet to be identified.

      Abstracte

      Clinically, HPV-positive oropharyngeal cancers (OPCs) have been shown to have a distinct prognosis, compared to HPV-negative tumours, particularly in survival rates and responses to treatment. These patients have better survival chances and improved prognosis, indicating that a more exhaustive knowledge of these distinctions would aid in the discovery of clinical approaches for both HPV-positive and negative tumours. Furthermore, there is increasing evidence that HPV-related oropharyngeal cancers constitute an epidemiological, molecular, and clinical distinct form as compared to non-HPV related ones therefore, the treatment of these specific subtype of oropharyngeal cancers should adopt a distinct clinical treatment pipeline. Our review will examine the current approaches for the diagnosis and treatment of OPC and discuss the relevance of de-escalation clinical trials in progress.

      Keywords

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      References

        • Momen-Heravi F.
        • Trachtenberg A.J.
        • Kuo W.P.
        • Cheng Y.S.
        Genomewide study of salivary MicroRNAs for detection of oral cancer.
        J Dent Res. 2014; 93: 86S-93S
        • Shield K.D.
        • Ferlay J.
        • Jemal A.
        • Sankaranarayanan R.
        • Chaturvedi A.K.
        • Bray F.
        • Soerjomataram I.
        The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012.
        CA: A Cancer J Clin. 2017; 67: 51-64
        • Taberna M.
        • Mena M.
        • Pavón M.A.
        • Alemany L.
        • Gillison M.L.
        • Mesía R.
        Human papillomavirus-related oropharyngeal cancer.
        Ann Oncol. 2017; 28: 2386-2398
        • Gougousis S.
        • Mouchtaropoulou E.
        • Besli I.
        • Vrochidis P.
        • Skoumpas I.
        • Constantinidis I.
        HPV-related oropharyngeal cancer and biomarkers based on epigenetics and microbiome profile.
        Front Cell Dev Biol. 2020; 8625330
        • Tanaka T.I.
        • Alawi F.
        Human papillomavirus and oropharyngeal cancer.
        Dent Clin North Am. 2018; 62: 111-120
        • Bansal A.
        • Singh M.P.
        • Rai B.
        Human papillomavirus-associated cancers: a growing global problem.
        Int J Appl Basic Med Res. 2016; 6: 84-89
        • Tian S.
        • Switchenko J.M.
        • Jhaveri J.
        • Cassidy R.J.
        • Ferris M.J.
        • Press R.H.
        • et al.
        Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: a propensity-scored analysis of the National Cancer Data Base.
        Cancer. 2019; 125: 2782-2793
        • Chaturvedi A.K.
        Global burden of human papillomavirus-positive head and neck cancers.
        Lancet Oncol. 2014; 15: 1282-1283
        • Iarc
        Human papillomaviruses.
        World Health Organisation. 2018; : 255-313
        • Bouvard V.
        • Baan R.
        • Straif K.
        • Grosse Y.
        • Secretan B.
        • Ghissassi F.E.
        • et al.
        Group WHOIAfRoCMW. A review of human carcinogens–Part B: biological agents.
        Lancet Oncol. 2009; 10: 321-322
        • Chaturvedi A.K.
        • Engels E.A.
        • Anderson W.F.
        • Gillison M.L.
        Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States.
        J Clin Oncol. 2008; 26: 612-619
        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • Laversanne M.
        • Soerjomataram I.
        • Jemal A.
        • et al.
        Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
        CA Cancer J Clin. 2021; 71: 209-249
        • Plummer M.
        • de Martel C.
        • Vignat J.
        • Ferlay J.
        • Bray F.
        • Franceschi S.
        Global burden of cancers attributable to infections in 2012: a synthetic analysis.
        Lancet Glob Health. 2016; 4: e609-e616
        • Ganguly N.
        • Parihar S.P.
        Human papillomavirus E6 and E7 oncoproteins as risk factors for tumorigenesis.
        J Biosci. 2009; 34: 113-123
        • Antonsson A.
        • de Souza M.
        • Wood Z.C.
        • Carroll A.
        • Van K.
        • Paterson L.
        • et al.
        Natural history of oral HPV infection: longitudinal analyses in prospective cohorts from Australia.
        Int J Cancer. 2021; 148: 1964-1972
        • Tumban E.
        A current update on human papillomavirus-associated head and neck cancers.
        Viruses. 2019; 11
        • Tran N.
        • Rose B.R.
        • O'Brien C.J.
        Role of human papillomavirus in the etiology of head and neck cancer.
        Head Neck. 2007; 29: 64-70
        • de Martel C.
        • Georges D.
        • Bray F.
        • Ferlay J.
        • Clifford G.M.
        Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis.
        Lancet Glob Health. 2020; 8: e180-e190
      1. Centers for Disease C, Prevention. Human papillomavirus-associated cancers - United States, 2004-2008. MMWR Morb Mortal Wkly Rep 2012;61:258-61.

        • Näsman A.
        • Du J.
        • Dalianis T.
        A global epidemic increase of an HPV-induced tonsil and tongue base cancer - potential benefit from a pan-gender use of HPV vaccine.
        J Intern Med. 2020; 287: 134-152
        • D'Souza G.
        • Kreimer A.R.
        • Viscidi R.
        • Pawlita M.
        • Fakhry C.
        • Koch W.M.
        • et al.
        Case-control study of human papillomavirus and oropharyngeal cancer.
        N Engl J Med. 2007; 356: 1944-1956
        • Campisi G.
        • Panzarella V.
        • Giuliani M.
        • Lajolo C.
        • Di Fede O.
        • Falaschini S.
        • et al.
        Human papillomavirus: its identity and controversial role in oral oncogenesis, premalignant and malignant lesions (review).
        Int J Oncol. 2007; 30: 813-823
        • Hong A.M.
        • Dobbins T.A.
        • Lee C.S.
        • Jones D.
        • Harnett G.B.
        • Armstrong B.K.
        • et al.
        Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy.
        Br J Cancer. 2010; 103: 1510-1517
        • Kreimer A.R.
        • Clifford G.M.
        • Boyle P.
        • Franceschi S.
        Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review.
        Cancer Epidemiol Biomarkers Prev. 2005; 14: 467-475
        • Maxwell J.H.
        • Kumar B.
        • Feng F.Y.
        • Worden F.P.
        • Lee J.S.
        • Eisbruch A.
        • Wolf G.T.
        • Prince M.E.
        • Moyer J.S.
        • Teknos T.N.
        • Chepeha D.B.
        • McHugh J.B.
        • Urba S.G.
        • Stoerker J.
        • Walline H.M.
        • Kurnit D.M.
        • Cordell K.G.
        • Davis S.J.
        • Ward P.D.
        • Bradford C.R.
        • Carey T.E.
        Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence.
        Clin Cancer Res. 2010; 16: 1226-1235
        • Dayyani F.
        • Etzel C.J.
        • Liu M.
        • Ho C.H.
        • Lippman S.M.
        • Tsao A.S.
        Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC).
        Head Neck Oncol. 2010; 2: 15
        • Ferlay J.
        • Colombet M.
        • Soerjomataram I.
        • Dyba T.
        • Randi G.
        • Bettio M.
        • et al.
        Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018.
        Eur J Cancer. 2018; 103: 356-387
        • Unsal A.A.
        • Unsal A.B.
        • Henn T.E.
        • Baredes S.
        • Eloy J.A.
        Cutaneous squamous cell carcinoma of the lip: a population-based analysis.
        Laryngoscope. 2018; 128: 84-90
        • Coca-Pelaz A.
        • Takes R.P.
        • Hutcheson K.
        • Saba N.F.
        • Haigentz M.
        • Bradford C.R.
        • et al.
        Head and neck cancer: a review of the impact of treatment delay on outcome.
        Adv Ther. 2018; 35: 153-160
        • Buexm L.A.
        • Soares-Lima S.C.
        • Brennan P.
        • Fernandes P.V.
        • de Souza Almeida Lopes M.
        • Nascimento de Carvalho F.
        • et al.
        Hpv impact on oropharyngeal cancer patients treated at the largest cancer center from Brazil.
        Cancer Lett. 2020; 477: 70-75
        • Viens L.J.
        • Henley S.J.
        • Watson M.
        • Markowitz L.E.
        • Thomas C.C.
        • Thompson T.D.
        • et al.
        Human papillomavirus-associated cancers - United States, 2008–2012.
        MMWR Morb Mortal Wkly Rep. 2016; 65: 661-666
        • Chan P.K.
        • Chor J.S.
        • Vlantis A.C.
        • Chow T.L.
        • Fung S.C.
        • Lau C.H.
        • et al.
        Smoking, human papillomavirus infection, and p53 mutation as risk factors in oropharyngeal cancer: a case-control study.
        Hong Kong Med J. 2017; 23: 12-16
        • Bukhari N.
        • Joseph J.P.
        • Hussain S.S.
        • Khan M.A.
        • Wakim M.J.Y.
        • Yahya E.B.
        • et al.
        Prevalence of human papilloma virus sub genotypes following head and neck squamous cell carcinomas in Asian continent, a systematic review article.
        Asian Pac J Cancer Prev. 2019; 20: 3269-3277
        • Taylor S.
        • Bunge E.
        • Bakker M.
        • Castellsague X.
        The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature.
        BMC Infect Dis. 2016; 16: 293
        • Curado M.P.
        • de Souza D.L.
        Cancer burden in Latin America and the Caribbean.
        Ann Glob Health. 2014; 80: 370-377
        • Pilleron S.
        • Cabasag C.J.
        • Ferlay J.
        • Bray F.
        • Luciani S.
        • Almonte M.
        • et al.
        Cervical cancer burden in Latin America and the Caribbean: where are we?.
        Int J Cancer. 2020; 147: 1638-1648
        • Menezes F.D.S.
        • Latorre M.d.R.D.d.O.
        • Conceição G.M.d.S.
        • Curado M.P.
        • Antunes J.L.F.
        • Toporcov T.N.
        • et al.
        The emerging risk of oropharyngeal and oral cavity cancer in HPV-related subsites in young people in Brazil.
        PLoS ONE. 2020; 15: e0232871
        • López R.V.M.
        • Levi J.E.
        • Eluf-Neto J.
        • Koifman R.J.
        • Koifman S.
        • Curado M.P.
        • et al.
        Human papillomavirus (HPV) 16 and the prognosis of head and neck cancer in a geographical region with a low prevalence of HPV infection.
        Cancer Causes Control. 2014; 25: 461-471
        • Machczyński P.
        • Majchrzak E.
        • Niewinski P.
        • Marchlewska J.
        • Golusiński W.
        A review of the 8th edition of the AJCC staging system for oropharyngeal cancer according to HPV status.
        Eur Arch Otorhinolaryngol. 2020; 277: 2407-2412
        • Lydiatt W.
        • O'Sullivan B.
        • Patel S.
        Major changes in head and neck staging for 2018.
        Am Soc Clin Oncol Educ Book. 2018; 38: 505-514
        • Zanoni D.K.
        • Patel S.G.
        • Shah J.P.
        Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications.
        Curr Oncol Rep. 2019; 21
        • Langendijk J.A.
        • Doornaert P.
        • Verdonck-de Leeuw I.M.
        • Leemans C.R.
        • Aaronson N.K.
        • Slotman B.J.
        Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy.
        J Clin Oncol. 2008; 26: 3770-3776
        • Schache A.G.
        • Liloglou T.
        • Risk J.M.
        • Filia A.
        • Jones T.M.
        • Sheard J.
        • Woolgar J.A.
        • Helliwell T.R.
        • Triantafyllou A.
        • Robinson M.
        • Sloan P.
        • Harvey-Woodworth C.
        • Sisson D.
        • Shaw R.J.
        Evaluation of human papilloma virus diagnostic testing in oropharyngeal squamous cell carcinoma: sensitivity, specificity, and prognostic discrimination.
        Clin Cancer Res. 2011; 17: 6262-6271
        • Salazar C.R.
        • Anayannis N.
        • Smith R.V.
        • Wang Y.
        • Haigentz M.
        • Garg M.
        • et al.
        Combined P16 and human papillomavirus testing predicts head and neck cancer survival.
        Int J Cancer. 2014; 135: 2404-2412
        • Lewis Jr., J.S.
        • Thorstad W.L.
        • Chernock R.D.
        • Haughey B.H.
        • Yip J.H.
        • Zhang Q.
        • et al.
        p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status.
        Am J Surg Pathol. 2010; 34: 1088-1096
        • Prigge E.-S.
        • Arbyn M.
        • von Knebel Doeberitz M.
        • Reuschenbach M.
        Diagnostic accuracy of p16(INK4a) immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis.
        Int J Cancer. 2017; 140: 1186-1198
        • Albers A.E.
        • Qian X.
        • Kaufmann A.M.
        • Coordes A.
        Meta analysis: HPV and p16 pattern determines survival in patients with HNSCC and identifies potential new biologic subtype.
        Sci Rep. 2017; 7: 16715
        • Nulton T.J.
        • Olex A.L.
        • Dozmorov M.
        • Morgan I.M.
        • Windle B.
        Analysis of The Cancer Genome Atlas sequencing data reveals novel properties of the human papillomavirus 16 genome in head and neck squamous cell carcinoma.
        Oncotarget. 2017; 8: 17684-17699
        • Venuti A.
        • Paolini F.
        HPV detection methods in head and neck cancer.
        Head Neck Pathol. 2012; 6: S63-S74
        • Jabbar S.
        • Strati K.
        • Shin M.K.
        • Pitot H.C.
        • Lambert P.F.
        Human papillomavirus type 16 E6 and E7 oncoproteins act synergistically to cause head and neck cancer in mice.
        Virology. 2010; 407: 60-67
        • Chi J.
        • Preeshagul I.R.
        • Sheikh-Fayyaz S.
        • Teckie S.
        • Kohn N.
        • Ziemba Y.
        • et al.
        Evaluating of HPV-DNA ISH as an adjunct to p16 testing in oropharyngeal cancer.
        Future Sci OA. 2020; 6: FSO606
        • Smeets S.J.
        • Hesselink A.T.
        • Speel E.-J.
        • Haesevoets A.
        • Snijders P.J.F.
        • Pawlita M.
        • et al.
        A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen.
        Int J Cancer. 2007; 121: 2465-2472
        • Thavaraj S.
        • Stokes A.
        • Guerra E.
        • Bible J.
        • Halligan E.
        • Long A.
        • et al.
        Evaluation of human papillomavirus testing for squamous cell carcinoma of the tonsil in clinical practice.
        J Clin Pathol. 2011; 64: 308-312
        • Agoston E.S.
        • Robinson S.J.
        • Mehra K.K.
        • Birch C.
        • Semmel D.
        • Mirkovic J.
        • et al.
        Polymerase chain reaction detection of HPV in squamous carcinoma of the oropharynx.
        Am J Clin Pathol. 2010; 134: 36-41
        • Molden T.
        • Kraus I.
        • Skomedal H.
        • Nordstrøm T.
        • Karlsen F.
        PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses.
        J Virol Methods. 2007; 142: 204-212
        • Chaturvedi A.K.
        • Engels E.A.
        • Pfeiffer R.M.
        • Hernandez B.Y.
        • Xiao W.
        • Kim E.
        • et al.
        Human papillomavirus and rising oropharyngeal cancer incidence in the United States.
        J Clin Oncol. 2011; 29: 4294-4301
        • Kellner M.J.
        • Koob J.G.
        • Gootenberg J.S.
        • Abudayyeh O.O.
        • Zhang F.
        SHERLOCK: nucleic acid detection with CRISPR nucleases.
        Nat Protoc. 2019; 14: 2986-3012
        • Ziai H.
        • Warner A.
        • Mundi N.
        • Patel K.
        • Chung E.J.
        • Howlett C.J.
        • et al.
        Does HPV subtype predict outcomes in head and neck cancers?.
        Int J Otolaryngol. 2021; 2021: 1-11
        • Cramer J.D.
        • Ferris R.L.
        • Kim S.
        • Duvvuri U.
        Primary surgery for human papillomavirus-associated oropharyngeal cancer: Survival outcomes with or without adjuvant treatment.
        Oral Oncol. 2018; 87: 170-176
        • Bonomo P.
        • Livi L.
        De-intensification for HPV positive oropharyngeal cancer: and yet it moves!: 2019 in review.
        Clin Transl Radiat Oncol. 2020; 22: 40-43
        • Nichols A.C.
        • Theurer J.
        • Prisman E.
        • Read N.
        • Berthelet E.
        • Tran E.
        • et al.
        Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial.
        Lancet Oncol. 2019; 20: 1349-1359
        • Hargreaves S.
        • Beasley M.
        • Hurt C.
        • Jones T.M.
        • Evans M.
        Deintensification of Adjuvant Treatment After Transoral Surgery in Patients With Human Papillomavirus-Positive Oropharyngeal Cancer: The Conception of the PATHOS Study and Its Development.
        Front Oncol. 2019; 9: 936
        • Economopoulou P.
        • Kotsantis I.
        • Psyrri A.
        HPV Positive Cancers. Special Issue about Head and Neck Cancers.
        Int J Mol Sci. 2020; : 21