{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T07:14:03Z","timestamp":1788678843384,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.<\/jats:p>","DOI":"10.3390\/microorganisms8101497","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T08:43:27Z","timestamp":1601369007000},"page":"1497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-6763","authenticated-orcid":false,"given":"Daisuke","family":"Inukai","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunpei","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-686X","authenticated-orcid":false,"given":"Yasushi","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsuki","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toyonori","family":"Tsuzuki","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9976","authenticated-orcid":false,"given":"Akiyoshi","family":"Takami","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4093-9533","authenticated-orcid":false,"given":"Tetsuya","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa0912217","article-title":"Human papilloma virus and survival of patients with oropharyngeal cancer","volume":"363","author":"Ang","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1002\/ijc.22851","article-title":"Survival of squamous cell carcinoma of the head and neck in relation to human papillomavirus infection: Review and meta-analysis","volume":"121","author":"Ragin","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1093\/annonc\/mdr006","article-title":"Survival and human papillomavirus in oropharynx cancer in TAX 324: A subset analysis from an international phase III trial","volume":"22","author":"Posner","year":"2011","journal-title":"Ann. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"93","DOI":"10.3322\/caac.21388","article-title":"The Eighth Edition AJCC Cancer Staging Manual:Continuing to Build a Bridge From a Population-Basedto a More \u201cPersonalized\u201d Approach to Cancer Staging","volume":"67","author":"Amin","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1200\/JCO.19.00441","article-title":"Role of Treatment Deintensification in the Management of p16+ Oropharyngeal Cancer: ASCO Provisional Clinical Opinion","volume":"37","author":"Adelstein","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1002\/cncr.28595","article-title":"What is the best treatment for patients with human papillomavirus-positive and -negative oropharyngeal cancer?","volume":"120","author":"Damien","year":"2014","journal-title":"Cancer"},{"key":"ref_7","first-page":"CD012939","article-title":"De-intensified adjuvant (chemo)radiotherapy versus standard adjuvant chemoradiotherapy post transoral minimally invasive surgery for resectable HPV-positive oropharyngeal carcinoma","volume":"12","author":"Howard","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3322\/caac.21343","article-title":"American Cancer Society head and neck cancer survivorship care guideline","volume":"66","author":"Cohen","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.ijrobp.2017.12.279","article-title":"Reirradiation for Head and Neck Cancer: The Who and the How","volume":"100","author":"Margalit","year":"2018","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.radonc.2015.10.014","article-title":"Induction chemotherapy followed by concurrent radio-chemotherapy versus concurrent radio-chemotherapy alone as treatment of locally advanced squamous cell carcinoma of the head and neck (HNSCC): A meta-analysis of randomized trials","volume":"118","author":"Budach","year":"2016","journal-title":"Radiother. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.canrad.2017.07.020","article-title":"[Role of induction chemotherapy in head and neck cancer: Cons]","volume":"21","author":"Huguet","year":"2017","journal-title":"Cancer Radiother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1097\/MOO.0000000000000143","article-title":"Oropharyngeal cancer treatment: The role of transoral surgery","volume":"23","author":"Hinni","year":"2015","journal-title":"Curr. Opin. Otolaryngol. Head Neck Surg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1002\/hed.26022","article-title":"Pathologic response to neoadjuvant chemotherapy in HPV-associated oropharynx cancer","volume":"42","author":"Sadeghi","year":"2020","journal-title":"Head Neck"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1002\/ijc.22980","article-title":"A novel algorithm for reliable detection of human papillomavirus in paraffin embedded head and neck cancer specimen","volume":"121","author":"Smeets","year":"2007","journal-title":"Int. J. Cancer."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Abd-El-Aziz, A.S., Carraher, C.E., Pittman, C.U., and Zeldin, M. (2008). Cisplatin Derivatives as Antiviral Agents. Inorganic and Organometallic Macromolecules, Springer.","DOI":"10.1007\/978-0-387-72947-3"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/978-3-642-38965-8_8","article-title":"The role of human papillomaviruses in oncogenesis","volume":"19","author":"Mighty","year":"2014","journal-title":"Recent Results Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/ijc.10580","article-title":"Escape of p53 protein from E6-mediated degradation in HeLa cells after cisplatin therapy","volume":"101","author":"Schloffer","year":"2002","journal-title":"Int. J. Cancer."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"N\u00e4sman, A., Romanitan, M., Nordfors, C., Gr\u00fcn, N., Johansson, H., Hammarstedt, L., Marklund, L., Munck-Wikland, E., Dalianis, T., and Ramqvist, T. (2012). Tumor Infiltrating CD8+ and Foxp3+ Lymphocytes Correlate to Clinical Outcome and Human Papillomavirus (HPV) Status in Tonsillar Cancer. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038711"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e000257","DOI":"10.1136\/esmoopen-2017-000257","article-title":"TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune cells in head and neck squamous cell carcinoma","volume":"3","author":"Leduc","year":"2018","journal-title":"ESMO Open."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.tranon.2016.10.002","article-title":"In Vitro and In Vivo Synergistic Therapeutic Effect of Cisplatin with Human Papillomavirus16 E6\/E7 CRISPR\/Cas9 on Cervical Cancer Cell Line","volume":"9","author":"Shuai","year":"2016","journal-title":"Transl. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.bpobgyn.2017.09.008","article-title":"Therapeutic HPV vaccine","volume":"47","author":"Hancock","year":"2018","journal-title":"Best Pract Res Clin. Obstet. Gvnecol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.oraloncology.2012.07.015","article-title":"Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer","volume":"49","author":"Huang","year":"2013","journal-title":"Oral Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S1470-2045(10)70017-6","article-title":"HPV-associated head and neck cancer: A virus-related cancer epidemic","volume":"11","author":"Marur","year":"2010","journal-title":"Lancet Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1200\/JCO.19.01007","article-title":"Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma","volume":"37","author":"Chera","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11912-019-0799-x","article-title":"Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and implications","volume":"21","author":"Zanoni","year":"2019","journal-title":"Curr. Oncol. Rep."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/10\/1497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:14:44Z","timestamp":1760177684000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/8\/10\/1497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":25,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["microorganisms8101497"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms8101497","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,29]]}}}