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Notably, HPV\n                    <jats:sup>+<\/jats:sup>\n                    TSCC and BOTSCC have a significantly better prognosis than their HPV\u2010negative counterparts when treated with current surgical options, radiotherapy, or intensified chemoradiotherapy. However, a cure is not achieved in 20% of patients with HPV\n                    <jats:sup>+<\/jats:sup>\n                    TSCC\/BOTSCC. Meanwhile, cured patients often present with severe chronic side effects. This necessitates novel tailored alternatives, such as targeted therapy, immune checkpoint inhibitors (ICIs), and treatment de\u2010escalation, together with better follow\u2010up. Current precision medicine therefore focuses on detecting predictive and driver cancer genes to better stratify patient treatment, provide those with poor prognostic markers targeted therapy, and select those with favorable markers for de\u2010escalated therapy. Moreover, detecting cell\u2010free HPV DNA (cfHPV DNA) in plasma before and after treatment has been attempted to improve follow\u2010up. In this context, this perspective discusses the significance of optimally defining HPV\n                    <jats:sup>+<\/jats:sup>\n                    status, which requires HPV DNA and p16\n                    <jats:sup>INKa<\/jats:sup>\n                    overexpression, using prognostic markers, such as high CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell counts and HPV E2 mRNA expression, tumor size, and following cfHPV DNA for patient selection for specific therapies. Clinical trials with ICI with\/without chemotherapy, targeted therapy with specific inhibitors\u2014such as phosphoinositide 3\u2010kinase and fibroblast growth factor receptor inhibitors\u2014or immune therapy with various HPV\u2010based vaccines for treating recurrences have yielded promising results.\n                  <\/jats:p>","DOI":"10.1111\/joim.20088","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T23:02:51Z","timestamp":1744930971000},"page":"608-629","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Therapeutic options for human papillomavirus\u2010positive tonsil and base of tongue cancer"],"prefix":"10.1111","volume":"297","author":[{"given":"Mark","family":"Zupancic","sequence":"first","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet  Stockholm Sweden"},{"name":"Medical Unit Head, Neck, Lung, and Skin Cancer, Theme Cancer Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ourania N.","family":"Kostopoulou","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Marklund","sequence":"additional","affiliation":[{"name":"Medical Unit Head, Neck, Lung, and Skin Cancer, Theme Cancer Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Surgical Sciences Section of Otolaryngology and Head and Neck Surgery Uppsala University  Uppsala Sweden"},{"name":"Division of Ear Nose and Throat Diseases Department of Clinical Sciences Intervention and Technology Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-2424","authenticated-orcid":false,"given":"Tina","family":"Dalianis","sequence":"additional","affiliation":[{"name":"Department of Oncology\u2010Pathology Karolinska Institutet  Stockholm Sweden"},{"name":"Medical Unit Head, Neck, Lung, and Skin Cancer, Theme Cancer Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"IARC monographs on the evaluation of carcinogenic risk to humans","author":"World Health Organization International Agency For Research On 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