{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:41:16Z","timestamp":1787665276459,"version":"build-2736575974"},"reference-count":65,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u2018Progetto Medio Ateneo\u2019 Univ. Sapienza","award":["RM11916B88DF74E7"],"award-info":[{"award-number":["RM11916B88DF74E7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Approximately 5\u201320% of HNSCC patients experience second primary cancers within the first 5 years of treatment, contributing to high mortality rates. Epidemiological evidence has linked a low dietary intake of antioxidants to an increased risk of cancer, especially squamous cell carcinoma, prompting research into their potential in neoplasm chemoprevention. Cigarette smoking is the primary risk factor for HNSCC, and a diet rich in antioxidants offers protective effects against head and neck cancer. Paradoxically, smokers, who are at the highest risk, tend to consume fewer antioxidant-rich fruits and vegetables. This has led to the hypothesis that integrating antioxidants into the diet could play a role in both primary and secondary prevention for at-risk individuals. Furthermore, some HNSCC patients use antioxidant supplements during chemotherapy or radiotherapy to manage side effects, but their impact on cancer outcomes remains uncertain. This systematic review explores the evidence for the potential use of antioxidants in preventing second primary cancers in HNSCC patients. In conclusion, none of the antioxidants tested so far (\u03b1-tocopherol, \u03b2-carotene, JP, Isotretinoin, interferon \u03b1-2a, vitamin E, retinyl palmitate, N-acetylcysteine) was effective in preventing second primary tumors in HNSCC patients, and they could only be used in reducing the side effects of radiotherapy. Further research is needed to better understand the interplay between antioxidants and cancer outcomes in this context.<\/jats:p>","DOI":"10.3390\/antiox12091753","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T21:34:12Z","timestamp":1694554452000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antioxidant Use after Diagnosis of Head and Neck Squamous Cell Carcinoma (HNSCC): A Systematic Review of Application during Radiotherapy and in Second Primary Cancer Prevention"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8762-3731","authenticated-orcid":false,"given":"Piero Giuseppe","family":"Meliante","sequence":"first","affiliation":[{"name":"Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0651-1816","authenticated-orcid":false,"given":"Carla","family":"Petrella","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6806-9715","authenticated-orcid":false,"given":"Marco","family":"Fiore","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Minni","sequence":"additional","affiliation":[{"name":"Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy"},{"name":"Division of Otolaryngology-Head and Neck Surgery, Ospedale San Camillo de Lellis, ASL Rieti-Sapienza University, Viale Kennedy, 02100 Rieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-9064","authenticated-orcid":false,"given":"Christian","family":"Barbato","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC), National Research Council (CNR), Department of Sense Organs DOS, Sapienza University of Rome, Viale del Policlinico 155, 00161 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3322\/canjclin.55.2.74","article-title":"Global Cancer Statistics, 2002. CA","volume":"55","author":"Parkin","year":"2005","journal-title":"Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/S0140-6736(08)60728-X","article-title":"Head and neck cancer","volume":"371","author":"Argiris","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0360-3016(89)90094-1","article-title":"Second malignancies in patients who have head and neck cancer: Incidence, effect on survival and implications based on the RTOG experience","volume":"17","author":"Cooper","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0360-3016(89)90095-3","article-title":"Second malignant tumors in patients with laryngeal carcinoma: Diagnosis, treatment, and prevention","volume":"17","author":"McDonald","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/0360-3016(89)90126-0","article-title":"Second malignant tumors in head and neck squamous cell carcinoma: The overshadowing threat for patients with early-stage disease","volume":"17","author":"Lippman","year":"1989","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1001\/archotol.1984.00800350006003","article-title":"Changing Patterns of Failure in Advanced Head and Neck Cancer","volume":"110","author":"Vikram","year":"1984","journal-title":"Arch. Otolaryngol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/jnci\/djj091","article-title":"Randomized phase III trial of low-dose isotretinoin for prevention of second primary tumors in stage I and II head and neck cancer patients","volume":"98","author":"Khuri","year":"2006","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.ejmech.2019.06.010","article-title":"Medicinal prospects of antioxidants: A review","volume":"178","author":"Neha","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.2174\/1381612825666190215121712","article-title":"Oxidative Stress and Cancer","volume":"24","author":"Klaunig","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF00051672","article-title":"Vegetables, fruit, and cancer. I. Epidemiology","volume":"2","author":"Steinmetz","year":"1991","journal-title":"Cancer Causes Control"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"559S","DOI":"10.1093\/ajcn\/78.3.559S","article-title":"Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk","volume":"78","author":"Riboli","year":"2003","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1200\/JCO.1994.12.4.851","article-title":"Cancer chemoprevention","volume":"12","author":"Lippman","year":"1994","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/0-306-48060-3_2","article-title":"Epidemiology, staging, and screening of head and neck cancer","volume":"114","author":"Argiris","year":"2003","journal-title":"Cancer Treat. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1056\/NEJMoa065497","article-title":"Case\u2013Control Study of Human Papillomavirus and Oropharyngeal Cancer","volume":"356","author":"Kreimer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1093\/annonc\/mdr548","article-title":"Nutrient-based dietary patterns and the risk of head and neck cancer: A pooled analysis in the International Head and Neck Cancer Epidemiology Consortium","volume":"23","author":"Edefonti","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s10552-011-9857-x","article-title":"Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium","volume":"23","author":"Chuang","year":"2012","journal-title":"Cancer Causes Control"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3200\/BMED.35.1.14-22","article-title":"A comparison of smokers\u2019 and nonsmokers\u2019 fruit and vegetable intake and relevant psychosocial factors","volume":"35","author":"McClure","year":"2009","journal-title":"Behav. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0002-8223(94)90370-0","article-title":"Dietary differences in smokers and nonsmokers from two southeastern New England communities","volume":"94","author":"McPhillips","year":"1994","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jada.2003.11.007","article-title":"Dietary patterns, smoking, and subclinical heart disease in women: Opportunities for primary prevention from the Framingham nutrition studies","volume":"104","author":"Millen","year":"2004","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1006\/pmed.1998.0289","article-title":"The food intake of smokers and nonsmokers: The role of partner\u2019s smoking behavior","volume":"27","author":"Osler","year":"1998","journal-title":"Prev. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8689","DOI":"10.1007\/s00520-022-07190-4","article-title":"Efficacy of oral and topical antioxidants in the prevention and management of oral mucositis in head and neck cancer patients: A systematic review and meta-analyses","volume":"30","author":"Raza","year":"2022","journal-title":"Support. Care Cancer"},{"key":"ref_22","first-page":"4295","article-title":"The antioxidant conundrum in cancer","volume":"63","author":"Seifried","year":"2003","journal-title":"Cancer Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1200\/JCO.2004.03.086","article-title":"Antioxidants and cancer therapy: A systematic review","volume":"22","author":"Ladas","year":"2004","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"889","DOI":"10.7326\/0003-4819-137-11-200212030-00010","article-title":"Advising patients who seek complementary and alternative medical therapies for cancer","volume":"137","author":"Weiger","year":"2002","journal-title":"Ann. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1053\/ctrv.2002.0260","article-title":"Pros and cons of antioxidant use during radiation therapy","volume":"28","author":"Prasad","year":"2002","journal-title":"Cancer Treat. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1093\/jnci\/dji095","article-title":"A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients","volume":"97","author":"Bairati","year":"2005","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1056\/NEJM199605023341802","article-title":"Effects of a Combination of Beta Carotene and Vitamin A on Lung Cancer and Cardiovascular Disease","volume":"334","author":"Omenn","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1002\/ijc.23200","article-title":"Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: A randomized trial among head and neck cancer patients","volume":"122","author":"Meyer","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_29","first-page":"1457","article-title":"Randomized trial of supplemental beta-carotene to prevent second head and neck cancer","volume":"61","author":"Mayne","year":"2001","journal-title":"Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1177\/1534735416684947","article-title":"A Randomized Double-Blind Placebo-Controlled Trial of Fruit and Vegetable Concentrates on Intermediate Biomarkers in Head and Neck Cancer","volume":"17","author":"Datta","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1001\/archotol.131.4.304","article-title":"Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: Long-term follow-up","volume":"131","author":"Richards","year":"2005","journal-title":"Arch. Otolaryngol. Head. Neck Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1200\/JCO.2001.19.12.3010","article-title":"Combined interferon-alfa, 13-cis-retinoic acid, and alpha-tocopherol in locally advanced head and neck squamous cell carcinoma: Novel bioadjuvant phase II trial","volume":"19","author":"Shin","year":"2001","journal-title":"J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1093\/jnci\/92.12.977","article-title":"EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups","volume":"92","author":"Dalesio","year":"2000","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_34","first-page":"255","article-title":"The chemoprevention of oral carcinoma with vitamin A and\/or N-acetylcysteine","volume":"43","author":"Cianfriglia","year":"1994","journal-title":"Minerva Stomatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0964-1955(96)00010-3","article-title":"Efficacy of vitamin A in the prevention of loco-regional recurrence and second primaries in head and neck cancer","volume":"32","author":"Jyothirmayi","year":"1996","journal-title":"Eur. J. Cancer B Oral Oncol."},{"key":"ref_36","first-page":"1895","article-title":"beta-carotene supplementation in patients radically treated for stage I-II head and neck cancer: Results of a randomized trial","volume":"10","author":"Toma","year":"2003","journal-title":"Oncol. Rep."},{"key":"ref_37","unstructured":"OCEBM Levels of Evidence Working Group (2011). The Oxford 2011 Levels of Evidence, Oxford Centre for Evidence-Based Medicine."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1001\/archsurg.1986.01400030019001","article-title":"Multiple Malignancies of the Lung and Head and Neck: Second Primary Tumor or Metastasis?","volume":"121","author":"Lefor","year":"1986","journal-title":"Arch. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJM199009203231205","article-title":"Prevention of Second Primary Tumors with Isotretinoin in Squamous-Cell Carcinoma of the Head and Neck","volume":"323","author":"Hong","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1056\/NEJM199605023341801","article-title":"Lack of Effect of Long-Term Supplementation with Beta Carotene on the Incidence of Malignant Neoplasms and Cardiovascular Disease","volume":"334","author":"Hennekens","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1001\/jama.290.4.476","article-title":"Incidence of Cancer and Mortality Following \u03b1-Tocopherol and \u03b2-Carotene Supplementation: A Postintervention Follow-up","volume":"290","author":"Virtamo","year":"2003","journal-title":"JAMA"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group (1994). The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers. N. Engl. J. Med., 330, 1029\u20131035.","DOI":"10.1056\/NEJM199404143301501"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/archotol.1983.00800250040009","article-title":"Head and Neck Cancer Survival and Life-style Change","volume":"109","author":"Stevens","year":"1983","journal-title":"Arch. Otolaryngol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1001\/jama.1971.03190170031005","article-title":"Cigarette Smoking and Cancer of the Mouth, Pharynx, and Larynx: A Continuing Study","volume":"218","author":"Moore","year":"1971","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_45","first-page":"823","article-title":"The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial","volume":"10","author":"Khuri","year":"2001","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1080\/01635580701397590","article-title":"Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients","volume":"59","author":"Meyer","year":"2007","journal-title":"Nutr. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ijo.2022.5386","article-title":"CYP11A1-derived vitamin D hydroxyderivatives as candidates for therapy of basal and squamous cell carcinomas","volume":"61","author":"Slominski","year":"2022","journal-title":"Int. J. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jsbmb.2014.11.010","article-title":"Novel activities of CYP11A1 and their potential physiological significance","volume":"151","author":"Slominski","year":"2015","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1124\/dmd.111.040071","article-title":"Production of 22-hydroxy metabolites of vitamin D 3 by cytochrome P450scc (CYP11A1) and analysis of their biological activities on skin cells","volume":"39","author":"Tuckey","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1096\/fj.12-208975","article-title":"In vivo evidence for a novel pathway of vitamin D 3 metabolism initiated by P450scc and modified by CYP27B1","volume":"26","author":"Slominski","year":"2012","journal-title":"FASEB J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/exd.12872","article-title":"Classical and non-classical metabolic transformation of vitamin D in dermal fibroblasts","volume":"25","author":"Slominski","year":"2016","journal-title":"Exp. Dermatol."},{"key":"ref_52","first-page":"3733","article-title":"Novel vitamin D hydroxyderivatives inhibit melanoma growth and show differential effects on normal melanocytes","volume":"32","author":"Slominski","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_53","first-page":"739","article-title":"20-Hydroxyvitamin D 3 inhibits proliferation of cancer cells with high efficacy while being non-toxic","volume":"32","author":"Wang","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e12824","DOI":"10.1111\/jpi.12824","article-title":"Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport","volume":"73","author":"Florido","year":"2022","journal-title":"J. Pineal Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"90545","DOI":"10.18632\/oncotarget.20079","article-title":"Melatonin as a potential inhibitory agent in head and neck cancer","volume":"8","author":"Yeh","year":"2017","journal-title":"Oncotarget"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Guerra-Librero, A., Fernandez-Gil, B.I., Florido, J., Martinez-Ruiz, L., Rodr\u00edguez-Santana, C., Shen, Y.Q., Garc\u00eda-Verdugo, J.M., L\u00f3pez-Rodr\u00edguez, A., Rusanova, I., and Qui\u00f1ones-Hinojosa, A. (2021). Melatonin targets metabolism in head and neck cancer cells by regulating mitochondrial structure and function. Antioxidants, 10.","DOI":"10.3390\/antiox10040603"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e12779","DOI":"10.1111\/jpi.12779","article-title":"Melatonin and verteporfin synergistically suppress the growth and stemness of head and neck squamous cell carcinoma through the regulation of mitochondrial dynamics","volume":"72","author":"Shin","year":"2022","journal-title":"J. Pineal Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1111\/cas.15338","article-title":"Melatonin inhibits EMT and PD-L1 expression through the ERK1\/2\/FOSL1 pathway and regulates anti-tumor immunity in HNSCC","volume":"113","author":"Luo","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-021-01888-9","article-title":"FGF19\/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis","volume":"40","author":"Lang","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e12461","DOI":"10.1111\/jpi.12461","article-title":"Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT\/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation","volume":"64","author":"Shen","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Guerra, J., and Devesa, J. (2022). Usefulness of melatonin and other compounds as antioxidants and epidrugs in the treatment of head and neck cancer. Antioxidants, 11.","DOI":"10.3390\/antiox11010035"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Meliante, P.G., Barbato, C., Zoccali, F., Ralli, M., Greco, A., de Vincentiis, M., Colizza, A., Petrella, C., Ferraguti, G., and Minni, A. (2022). Programmed Cell Death-Ligand 1 in Head and Neck Squamous Cell Carcinoma: Molecular Insights, Preclinical and Clinical Data, and Therapies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315384"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Meliante, P.G., Zoccali, F., de Vincentiis, M., Ralli, M., Petrella, C., Fiore, M., Minni, A., and Barbato, C. (2023). Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma. Diagnostics, 13.","DOI":"10.3390\/diagnostics13050862"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.tins.2023.01.003","article-title":"How cancer hijacks the body\u2019s homeostasis through the neuroendocrine system","volume":"46","author":"Slominski","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/9\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:49:34Z","timestamp":1760129374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/9\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,12]]},"references-count":65,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["antiox12091753"],"URL":"https:\/\/doi.org\/10.3390\/antiox12091753","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,12]]}}}