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HPV-Related Oropharyngeal Squamous Cell Carcinoma
Surjith Vattoth, MD, FRCR; Philip R. Chapman, MD
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KEY FACTS

  • Terminology

    • Imaging

      • Top Differential Diagnoses

        • Pathology

          • Clinical Issues

            TERMINOLOGY

            • Abbreviations

              • Human papillomavirus (HPV)
              • Oropharyngeal squamous cell carcinoma (OPSCCa)
              • American Joint Committee on Cancer (AJCC)
            • Synonyms

              • HPV-mediated [p16(+)] oropharyngeal carcinoma
            • Definitions

              • Subcategory of OPSCCa caused by HPV infection
                • Overall better prognosis than conventional SCCa; patients with OPSCCa-HPV may be candidates for less aggressive therapy compared to HPV-negative OPSCCa
              • New TNM classification exclusively for HPV-related OPSCCa added in latest 8th edition (2017) of AJCC Cancer Staging Manual

            IMAGING

            • General Features

              • CT Findings

                • MR Findings

                  • Ultrasonographic Findings

                    • Nuclear Medicine Findings

                      • Imaging Recommendations

                        DIFFERENTIAL DIAGNOSIS

                          PATHOLOGY

                          • General Features

                            • Staging, Grading, & Classification

                              • Gross Pathologic & Surgical Features

                                • Microscopic Features

                                  • Human Papillomavirus

                                    CLINICAL ISSUES

                                    • Presentation

                                      • Demographics

                                        • Natural History & Prognosis

                                          • Treatment

                                            DIAGNOSTIC CHECKLIST

                                            • Consider

                                              • Image Interpretation Pearls

                                                • Reporting Tips

                                                  Selected References

                                                  1. Chidambaram S et al: Prognostic significance of smoking in human papillomavirus-positive oropharyngeal cancer under American Joint Committee on Cancer Eighth Edition Stage. Laryngoscope. 130(8):1961-6, 2020
                                                  2. Hoffmann M et al: HPV and oropharyngeal cancer in the Eighth Edition of the TNM Classification: pitfalls in practice. Transl Oncol. 12(8):1108-12, 2019
                                                  3. Parvathaneni U et al: Advances in diagnosis and multidisciplinary management of oropharyngeal squamous cell carcinoma: state of the art. Radiographics. 39(7):2055-68, 2019
                                                  4. Ravanelli M et al: Correlation between human papillomavirus status and quantitative MR imaging parameters including diffusion-weighted imaging and texture features in oropharyngeal carcinoma. AJNR Am J Neuroradiol. 39(10):1878-83, 2018
                                                  5. Lydiatt WM et al: Head and neck cancers-major changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J Clin. 67(2):122-37, 2017
                                                  6. Anantharaman D et al: Combined effects of smoking and HPV16 in oropharyngeal cancer. Int J Epidemiol. ePub, 2016
                                                  7. Gooi Z et al: The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. Laryngoscope. 126(4):894-900, 2016
                                                  8. Horne ZD et al: Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas. Cancer. 122(13):2021-30, 2016
                                                  9. Sano D et al: The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma. Int J Clin Oncol. ePub, 2016
                                                  10. Truong Lam M et al: Challenges in establishing the diagnosis of human papillomavirus-related oropharyngeal carcinoma. Laryngoscope. ePub, 2016
                                                  11. Vainshtein JM et al: Matted nodes: High distant-metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus-related oropharyngeal cancer. Head Neck. 38 Suppl 1:E805-14, 2016
                                                  12. Baxter M et al: Retropharyngeal lymph node involvement in human papillomavirus-associated oropharyngeal squamous cell carcinoma. Laryngoscope. 125(11):2503-8, 2015
                                                  13. Hinni ML et al: Oropharyngeal cancer treatment: the role of transoral surgery. Curr Opin Otolaryngol Head Neck Surg. 23(2):132-8, 2015
                                                  14. Kendi AT et al: Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status? Clin Nucl Med. 40(3):e196-200, 2015
                                                  15. Samuels SE et al: Impact of retropharyngeal adenopathy on distant control and survival in HPV-related oropharyngeal cancer treated with chemoradiotherapy. Radiother Oncol. 116(1):75-81, 2015
                                                  16. Deschler DG et al: The "new" head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol Head Neck Surg. 151(3):375-80, 2014
                                                  17. Koshkareva Y et al: Predictive accuracy of first post-treatment PET/CT in HPV-related oropharyngeal squamous cell carcinoma. Laryngoscope. 124(8):1843-7, 2014
                                                  18. Subramaniam RM et al: PET/CT imaging and human papilloma virus-positive oropharyngeal squamous cell cancer: evolving clinical imaging paradigm. J Nucl Med. 55(3):431-8, 2014
                                                  19. Tahari AK et al: FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med. 39(3):225-31, 2014
                                                  20. Trinkaus ME et al: Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer. J Med Imaging Radiat Oncol. 58(1):89-97, 2014
                                                  21. Cantrell SC et al: Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol. 34(10):2005-9, 2013
                                                  22. Genden EM et al: Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know. Eur Arch Otorhinolaryngol. Epub ahead of print, 2012
                                                  23. Loevner LA et al: Transoral robotic surgery in head and neck cancer: what radiologists need to know about the cutting edge. Radiographics. 33(6):1759-79, 2013
                                                  24. Corey AS et al: Radiographic imaging of human papillomavirus related carcinomas of the oropharynx. Head Neck Pathol. 6 Suppl 1:S25-40, 2012
                                                  25. Haerle SK et al: Contrast-enhanced ¹⁸F-FDG-PET/CT for the assessment of necrotic lymph node metastases. Head Neck. 33(3):324-9, 2011
                                                  26. Zhang I et al: The benefit of early PET/CT surveillance in HPV-associated head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 137(11):1106-11, 2011
                                                  27. Ang KK et al: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 363(1):24-35, 2010
                                                  28. Attner P et al: The role of human papillomavirus in the increased incidence of base of tongue cancer. Int J Cancer. 126(12):2879-84, 2010
                                                  29. Chaturvedi AK: Beyond cervical cancer: burden of other HPV-related cancers among men and women. J Adolesc Health. 46(4 Suppl):S20-6, 2010
                                                  30. Glombitza F et al: HPV status in head and neck tumors. Pathol Res Pract. 206(4):229-34, 2010
                                                  31. Heck JE et al: Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Int J Epidemiol. 39(1):166-81, 2010
                                                  32. Maxwell JH et al: Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 16(4):1226-35, 2010
                                                  33. Singhi AD et al: Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 34(6):800-5, 2010
                                                  34. StatBite: Proportion of specific cancers caused by HPV. J Natl Cancer Inst. 102(12):839, 2010
                                                  35. Chung CH et al: Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 15(22):6758-62, 2009
                                                  36. Gillespie MB et al: Human papillomavirus and oropharyngeal cancer: what you need to know in 2009. Curr Treat Options Oncol. 10(5-6):296-307, 2009
                                                  37. Gillison ML: HPV and prognosis for patients with oropharynx cancer. Eur J Cancer. 45 Suppl 1:383-5, 2009
                                                  38. Gillison ML: Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV infection. Curr Opin Oncol. 21(5):439-44, 2009
                                                  39. Hudgins PA, Gillison M. Second branchial cleft cyst: not!! AJNR Am J Neuroradiol. 30(9):1628-9, 2009
                                                  40. Luginbuhl A et al: Prevalence, morphology, and prognosis of human papillomavirus in tonsillar cancer. Ann Otol Rhinol Laryngol. 118(10):742-9, 2009
                                                  41. Printz C: CancerScope: HPV vaccine for boys and men? It could help reduce incidence of cervical and head and neck cancers. Cancer. 115(22):5129-30, 2009
                                                  42. Printz C: CancerScope: Patients with HPV-linked throat cancer fare better than others. Cancer. 115(22):5131, 2009
                                                  43. Settle K et al: Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev Res (Phila Pa). 2(9):776-81, 2009
                                                  44. Straetmans JM et al: Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas. Laryngoscope. 119(10):1951-7, 2009
                                                  45. Goldenberg D et al: Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon. Head Neck. 30(7):898-903, 2008
                                                  46. D'Souza G et al: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 356(19):1944-56, 2007
                                                  47. Current College of American Pathologists (CAP) Guidelines: Human Papillomavirus Testing in Head and Neck Carcinomas. https://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/human-papillomavirus-testing-in-head-and-neck-carcinomas
                                                  Related Anatomy
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                                                  Related Differential Diagnoses
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                                                  References
                                                  Tables

                                                  Tables

                                                  KEY FACTS

                                                  • Terminology

                                                    • Imaging

                                                      • Top Differential Diagnoses

                                                        • Pathology

                                                          • Clinical Issues

                                                            TERMINOLOGY

                                                            • Abbreviations

                                                              • Human papillomavirus (HPV)
                                                              • Oropharyngeal squamous cell carcinoma (OPSCCa)
                                                              • American Joint Committee on Cancer (AJCC)
                                                            • Synonyms

                                                              • HPV-mediated [p16(+)] oropharyngeal carcinoma
                                                            • Definitions

                                                              • Subcategory of OPSCCa caused by HPV infection
                                                                • Overall better prognosis than conventional SCCa; patients with OPSCCa-HPV may be candidates for less aggressive therapy compared to HPV-negative OPSCCa
                                                              • New TNM classification exclusively for HPV-related OPSCCa added in latest 8th edition (2017) of AJCC Cancer Staging Manual

                                                            IMAGING

                                                            • General Features

                                                              • CT Findings

                                                                • MR Findings

                                                                  • Ultrasonographic Findings

                                                                    • Nuclear Medicine Findings

                                                                      • Imaging Recommendations

                                                                        DIFFERENTIAL DIAGNOSIS

                                                                          PATHOLOGY

                                                                          • General Features

                                                                            • Staging, Grading, & Classification

                                                                              • Gross Pathologic & Surgical Features

                                                                                • Microscopic Features

                                                                                  • Human Papillomavirus

                                                                                    CLINICAL ISSUES

                                                                                    • Presentation

                                                                                      • Demographics

                                                                                        • Natural History & Prognosis

                                                                                          • Treatment

                                                                                            DIAGNOSTIC CHECKLIST

                                                                                            • Consider

                                                                                              • Image Interpretation Pearls

                                                                                                • Reporting Tips

                                                                                                  Selected References

                                                                                                  1. Chidambaram S et al: Prognostic significance of smoking in human papillomavirus-positive oropharyngeal cancer under American Joint Committee on Cancer Eighth Edition Stage. Laryngoscope. 130(8):1961-6, 2020
                                                                                                  2. Hoffmann M et al: HPV and oropharyngeal cancer in the Eighth Edition of the TNM Classification: pitfalls in practice. Transl Oncol. 12(8):1108-12, 2019
                                                                                                  3. Parvathaneni U et al: Advances in diagnosis and multidisciplinary management of oropharyngeal squamous cell carcinoma: state of the art. Radiographics. 39(7):2055-68, 2019
                                                                                                  4. Ravanelli M et al: Correlation between human papillomavirus status and quantitative MR imaging parameters including diffusion-weighted imaging and texture features in oropharyngeal carcinoma. AJNR Am J Neuroradiol. 39(10):1878-83, 2018
                                                                                                  5. Lydiatt WM et al: Head and neck cancers-major changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual. CA Cancer J Clin. 67(2):122-37, 2017
                                                                                                  6. Anantharaman D et al: Combined effects of smoking and HPV16 in oropharyngeal cancer. Int J Epidemiol. ePub, 2016
                                                                                                  7. Gooi Z et al: The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. Laryngoscope. 126(4):894-900, 2016
                                                                                                  8. Horne ZD et al: Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas. Cancer. 122(13):2021-30, 2016
                                                                                                  9. Sano D et al: The molecular mechanism of human papillomavirus-induced carcinogenesis in head and neck squamous cell carcinoma. Int J Clin Oncol. ePub, 2016
                                                                                                  10. Truong Lam M et al: Challenges in establishing the diagnosis of human papillomavirus-related oropharyngeal carcinoma. Laryngoscope. ePub, 2016
                                                                                                  11. Vainshtein JM et al: Matted nodes: High distant-metastasis risk and a potential indication for intensification of systemic therapy in human papillomavirus-related oropharyngeal cancer. Head Neck. 38 Suppl 1:E805-14, 2016
                                                                                                  12. Baxter M et al: Retropharyngeal lymph node involvement in human papillomavirus-associated oropharyngeal squamous cell carcinoma. Laryngoscope. 125(11):2503-8, 2015
                                                                                                  13. Hinni ML et al: Oropharyngeal cancer treatment: the role of transoral surgery. Curr Opin Otolaryngol Head Neck Surg. 23(2):132-8, 2015
                                                                                                  14. Kendi AT et al: Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status? Clin Nucl Med. 40(3):e196-200, 2015
                                                                                                  15. Samuels SE et al: Impact of retropharyngeal adenopathy on distant control and survival in HPV-related oropharyngeal cancer treated with chemoradiotherapy. Radiother Oncol. 116(1):75-81, 2015
                                                                                                  16. Deschler DG et al: The "new" head and neck cancer patient-young, nonsmoker, nondrinker, and HPV positive: evaluation. Otolaryngol Head Neck Surg. 151(3):375-80, 2014
                                                                                                  17. Koshkareva Y et al: Predictive accuracy of first post-treatment PET/CT in HPV-related oropharyngeal squamous cell carcinoma. Laryngoscope. 124(8):1843-7, 2014
                                                                                                  18. Subramaniam RM et al: PET/CT imaging and human papilloma virus-positive oropharyngeal squamous cell cancer: evolving clinical imaging paradigm. J Nucl Med. 55(3):431-8, 2014
                                                                                                  19. Tahari AK et al: FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: characteristics of human papillomavirus-positive and -negative tumors. Clin Nucl Med. 39(3):225-31, 2014
                                                                                                  20. Trinkaus ME et al: Correlation of p16 status, hypoxic imaging using [18F]-misonidazole positron emission tomography and outcome in patients with loco-regionally advanced head and neck cancer. J Med Imaging Radiat Oncol. 58(1):89-97, 2014
                                                                                                  21. Cantrell SC et al: Differences in imaging characteristics of HPV-positive and HPV-Negative oropharyngeal cancers: a blinded matched-pair analysis. AJNR Am J Neuroradiol. 34(10):2005-9, 2013
                                                                                                  22. Genden EM et al: Human papillomavirus and oropharyngeal squamous cell carcinoma: what the clinician should know. Eur Arch Otorhinolaryngol. Epub ahead of print, 2012
                                                                                                  23. Loevner LA et al: Transoral robotic surgery in head and neck cancer: what radiologists need to know about the cutting edge. Radiographics. 33(6):1759-79, 2013
                                                                                                  24. Corey AS et al: Radiographic imaging of human papillomavirus related carcinomas of the oropharynx. Head Neck Pathol. 6 Suppl 1:S25-40, 2012
                                                                                                  25. Haerle SK et al: Contrast-enhanced ¹⁸F-FDG-PET/CT for the assessment of necrotic lymph node metastases. Head Neck. 33(3):324-9, 2011
                                                                                                  26. Zhang I et al: The benefit of early PET/CT surveillance in HPV-associated head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 137(11):1106-11, 2011
                                                                                                  27. Ang KK et al: Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 363(1):24-35, 2010
                                                                                                  28. Attner P et al: The role of human papillomavirus in the increased incidence of base of tongue cancer. Int J Cancer. 126(12):2879-84, 2010
                                                                                                  29. Chaturvedi AK: Beyond cervical cancer: burden of other HPV-related cancers among men and women. J Adolesc Health. 46(4 Suppl):S20-6, 2010
                                                                                                  30. Glombitza F et al: HPV status in head and neck tumors. Pathol Res Pract. 206(4):229-34, 2010
                                                                                                  31. Heck JE et al: Sexual behaviours and the risk of head and neck cancers: a pooled analysis in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Int J Epidemiol. 39(1):166-81, 2010
                                                                                                  32. Maxwell JH et al: Tobacco use in human papillomavirus-positive advanced oropharynx cancer patients related to increased risk of distant metastases and tumor recurrence. Clin Cancer Res. 16(4):1226-35, 2010
                                                                                                  33. Singhi AD et al: Lymphoepithelial-like carcinoma of the oropharynx: a morphologic variant of HPV-related head and neck carcinoma. Am J Surg Pathol. 34(6):800-5, 2010
                                                                                                  34. StatBite: Proportion of specific cancers caused by HPV. J Natl Cancer Inst. 102(12):839, 2010
                                                                                                  35. Chung CH et al: Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res. 15(22):6758-62, 2009
                                                                                                  36. Gillespie MB et al: Human papillomavirus and oropharyngeal cancer: what you need to know in 2009. Curr Treat Options Oncol. 10(5-6):296-307, 2009
                                                                                                  37. Gillison ML: HPV and prognosis for patients with oropharynx cancer. Eur J Cancer. 45 Suppl 1:383-5, 2009
                                                                                                  38. Gillison ML: Oropharyngeal cancer: a potential consequence of concomitant HPV and HIV infection. Curr Opin Oncol. 21(5):439-44, 2009
                                                                                                  39. Hudgins PA, Gillison M. Second branchial cleft cyst: not!! AJNR Am J Neuroradiol. 30(9):1628-9, 2009
                                                                                                  40. Luginbuhl A et al: Prevalence, morphology, and prognosis of human papillomavirus in tonsillar cancer. Ann Otol Rhinol Laryngol. 118(10):742-9, 2009
                                                                                                  41. Printz C: CancerScope: HPV vaccine for boys and men? It could help reduce incidence of cervical and head and neck cancers. Cancer. 115(22):5129-30, 2009
                                                                                                  42. Printz C: CancerScope: Patients with HPV-linked throat cancer fare better than others. Cancer. 115(22):5131, 2009
                                                                                                  43. Settle K et al: Racial survival disparity in head and neck cancer results from low prevalence of human papillomavirus infection in black oropharyngeal cancer patients. Cancer Prev Res (Phila Pa). 2(9):776-81, 2009
                                                                                                  44. Straetmans JM et al: Human papillomavirus reduces the prognostic value of nodal involvement in tonsillar squamous cell carcinomas. Laryngoscope. 119(10):1951-7, 2009
                                                                                                  45. Goldenberg D et al: Cystic lymph node metastasis in patients with head and neck cancer: An HPV-associated phenomenon. Head Neck. 30(7):898-903, 2008
                                                                                                  46. D'Souza G et al: Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 356(19):1944-56, 2007
                                                                                                  47. Current College of American Pathologists (CAP) Guidelines: Human Papillomavirus Testing in Head and Neck Carcinomas. https://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/human-papillomavirus-testing-in-head-and-neck-carcinomas