- Original Article
- Open Access
Value of vitamin D assessment in patients with head and neck squamous cell cancer before treatment
The Egyptian Journal of Otolaryngology volume 32, pages279–286(2016)
The 5-year survival of patients with head and neck squamous cell carcinoma (HNSCC) has not changed dramatically over the last decades despite the use of various therapeutic modalities, including surgery and/or chemoradiation. Thus, new approaches remain necessary to prevent cancer, reduce recurrence, and improve treatment with reduction of its side effects. There is recent evidence that vitamin D promotes cell differentiation and decreases cell proliferation, invasion, angiogenesis, and metastasis. Thus, it has been hypothesized that vitamin D may protect against cancer at multiple sites.
The aim of this study was to evaluate serum level of vitamin D (VD), calcium, and phosphate in patients with HNSCC before treatment as a step in studying its impact on HNSCC development and progression.
Type of the study
This prospective study was conducted between March 2013 and October 2014 at Ain Shams University Hospitals, Cairo, Egypt.
Patients and methods
The study included 80 participants categorized into two groups. Group A included 50 (36 males and 14 females) patients with various HNSCC sites; their median age was 54.8 ± 12.7 years. Group B included 30 (20 males and 10 females) sex-matched and age-matched healthy volunteers as controls; their mean age was 50.5 ± 12.0 years.
The median VD level in group A was 40.35 (31.9–55) and for group B it was 118.75 (55.0–175) (P < 0.001), indicating a significant decrease of VD in group A than in group B. VD deficiency (<37.5 nmol/ml) in group A was 42%, which was significantly more than that in group B, which was only 3%.
This study showed that vitamin D deficiency is prominent in patients with head and neck squamous cell carcinoma before treatment than in controls. Although it may expose the patients to increased risk of therapy-related morbidity and poor outcome, it may constitute an inexpensive prophylactic and cost-effective option in the therapeutic armamentarium as a synergistic agent to traditional treatment options.
National Cancer Institute. Surveillance epidemiology and end results. Available at: http://seer.cancer.gov/statfacts/html/oralcav.html/. [Last accessed on 21 May 2013].
Buttigliero C, Monagheddu C, Petroni P, Saini A, Dogliotti L, Ciccone G, Berruti A. Prognostic role of vitamin d status and efficacy of vitamin D supplementation in cancer patients: a systematic review. Oncologist 2011; 16: 1215–1227.
Meier JD, Enepekides DJ, Poirier B, Bradley CA, Albala JS, Farwell DG. Treatment with 1-α,25-dihydroxyvitamin D3 (vitamin D3) to inhibit carcinogenesis in the hamster buccal pouch model. Arch Otolaryngol 2007; 133: 1149–1152.
Helzlsouer KJ. Overview of the cohort consortium vitamin D pooling project of rarer cancers. Am J Epidemiol 2010; 172: 4–9.
Wiers KM, Lathers DM, Wright MA, Young MR. Vitamin D3 treatment to diminish the levels of immune suppressive CD34+ cells increases the effectiveness of adoptive immunotherapy. J Immunother 2000; 23: 115–124.
Ma Y, Zhang P, Wang F, Yang J, Liu Z, Qin H. Association between vitamin D and risk of colorectal cancer: a systematic review of prospective studies. J Clin Oncol 2011; 29: 3775–3782.
Bolland MJ, Grey A, Gamble GD, Reid IR. Calcium and vitamin D supplements and health outcomes: a reanalysis of the Women’s Health Initiative (WHI) limited-access data set. Am J Clin Nutr 2011; 94: 1144–1149.
Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res 2011; 13: R74.
Chiang KC, Yeh CN, Chen HY, Lee JM, Juang HH, Chen MF et al. 19-Nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10) is a potent cell growth regulator with enhanced chemotherapeutic potency in liver cancer cells. Steroids 2011; 76: 1513–1519.
Kovalenko PL, Zhang Z, Yu JG, Li Y, Clinton SK, Fleet JC. Dietary vitamin D and vitamin D receptor level modulate epithelial cell proliferation and apoptosis in the prostate. Cancer Prev Res 2011; 4: 1617–1725.
Kulbersh JS, Day TA, Gillespie MB, Young MR. 1α,25-Dihydroxyvitamin D3 to skew intratumoral levels of immune inhibitory CD34+ progenitor cells into dendritic cells. Otolaryngol Head Neck Surg 2009; 140: 235–240.
Lin R, Nagai Y, Sladek R, Bastien Y, Ho J, Petrecca K et al. Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol 2002; 16: 1243–1256.
Fleet JC, DeSmet M, Johnson R, Li Y. Vitamin D and cancer: a review of molecular mechanisms. Biochem J 2012; 441: 61–76.
Orell-Kotikangas H, Schwab U, Österlund P, Saarilahti K, Mäkitie O, Mäkitie AA. High prevalence of vitamin D insufficiency in patients with head and neck cancer at diagnosis. Head Neck 2012; 34: 1450–1455.
Faupel-Badger JM, Diaw L, Albanes D, Virtamo J, Woodson K, Tangrea JA. Lack of association between serum levels of 25-hydroxyvitamin D and the subsequent risk of prostate cancer in Finnish men. Cancer Epidemiol Biomarkers Prev 2007; 16: 2784–2786.
Meyer F, Liu G, Douville P, Samson E, Xu W, Adjei A, Bairati I. Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients. Int J Cancer 2011; 128: 1741–1746.
Fakih MG, Trump DL, Johnson CS, Tian L, Muindi J, Sunga AY. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int J Colorectal Dis 2009; 24: 219–224.
Akhter J, Chen X, Bowrey P, Bolton EJ, Morris DL. Vitamin D3 analog, EB1089, inhibits growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model. Dis Colon Rectum 1997; 40: 317–321.
Abe-Hashimoto J, Kikuchi T, Matsumoto T, Nishii Y, Ogata E, Ikeda K. Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen. Cancer Res 1993; 53: 2534–2537.
Dalhoff K, Dancey J, Astrup L, Skovsgaard T, Hamberg KJ, Lofts FJ et al. A phase II study of the vitamin D analogue seocalcitol in patients with inoperable hepatocellular carcinoma. Br J Cancer 2003; 89: 252–257.
Giovannucci E, Liu Y, Rimm EB, Hollis BW, Fuchs CS, Stampfer MJ, Willett WC. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst 2006; 98: 451–459.
Cui Y, Rohan TE. Vitamin D, calcium, and breast cancer risk: a review. Cancer Epidemiol Biomarkers Prev 2006; 15: 1427–1437.
Schwartz GG. Vitamin D and the epidemiology of prostate cancer. Semin Dial 2005; 18: 276–289.
Schwartz GG, Skinner HG. Vitamin D status and cancer: new insights. Curr Opin Clin Nutr Metab Care 2007; 10: 6–11.
Holick MF. Vitamin D The underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002; 9: 87–98.
Holick MF. Favus MJ. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. Primer on the metabolic bone diseases and disorders of mineral metabolism 5th ed. Washington, DC:American Society for Bone and Mineral Research; 2003. 129–137.
Gregori S, Giarratana N, Smiroldo S, Uskokovic M, Adorini L. A 1, 25-dihydroxyvitamin D3 analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes 2002; 51: 1367–1374.
Young MR, Day TA. Immune regulatory activity of vitamin D3 in head and neck cancer. Cancers (Basel) 2013; 5: 1072–1085.
Li J, Jin D, Fu S, Mei G, Zhou J, Lei L et al. Insulin-like growth factor binding protein-3 modulates osteoblast differentiation via interaction with vitamin D receptor. Biochem Biophys Res Commun 2013; 436: 632–637.
Lathers DM, Lubbers E, Wright MA, Young MRI. Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients. J Leukoc Biol 1999; 65: 623–628.
Ginde AA, Liu MC, Camargo CAJr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Int Med 2009; 169:626–632.
Godar DE, Pope SJ, Grant WB, Holick MF. Solar UV doses of adult Americans and vitamin D3 production. Dermatoendocrinol 2011; 3: 243–250.
Walsh JE, Clark AM, Day TA, Gillespie MB, Young MR. Use of 1α,25-dihydroxyvitamin D3 treatment to stimulate immune infiltration into head and neck squamous cell carcinoma. Human Immunol 2010; 71: 659–665.
Moreno J, Krishnan AV, Peehl DM, Feldman D. Mechanisms of vitamin D-mediated growth inhibition in prostate cancer cells: inhibition of the prostaglandin pathway. Anticancer Res 2006; 26: 2525–2530.
Thill M, Fischer D, Hoellen F, Kelling K, Dittmer C, Landt S et al. Prostaglandin metabolising enzymes and PGE2 are inversely correlated with vitamin D receptor and 25(OH)2D3 in breast cancer. Anticancer Res 2010; 30: 1673–1679.
Thill M, Fischer D, Kelling K, Hoellen F, Dittmer C, Hornemann A et al. Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25(OH2)D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients. J Steroid Biochem Mol Biol 2010; 121: 387–390.
Dong J, Wong SL, Lau CW, Liu J, Wang YX, He ZD et al. Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor. Kidney Int 2013; 84: 54–63.
Renkonen J, Wolff H, Paavonen T. Expression of cyclo-oxygenase-2 in human tongue carcinoma and its precursor lesions. Virchows Arch 2002; 440: 594–597.
Mulligan JK, Day TA, Gillespie MB, Rosenzweig SA, Young MR. Secretion of vascular endothelial growth factor by oral squamous cell carcinoma cells skews endothelial cells to suppress T-cell functions. Human Immunol 2009; 70: 375–382.
Wanebo HJ, Riley T, Karz D, Pace RC, Johns ME, Cantrell RW. Indomethacin sensitive suppressor-cell activity in head and neck cancer patients. The role of the adherent mononuclear cell. Cancer 1988; 61: 462–474.
Dovedi SJ, Kirby JA, Davies BR, Leung H, Kelly JD. Celecoxib has potent antitumour effects as a single agent and in combination with BCG immunotherapy in a model of urothelial cell carcinoma. Eur Urol 2008; 54: 621–630.
Young MR, Newby M. Garaci E, Santoro MG. Differential induction of macrophage prostaglandin E2 secretion and suppressor activity by Lewis lung carcinoma variants. Prostaglandins and cancer. Berlin, Heidelberg, Germany:Springer-Verlag; 1987. 273–276.
Gillespie MB, Moody MW, Lee FS, Poole LJ, Hornig JD, Lathers D et al. Head and neck cancer recurrence and mortality in nonselective cyclooxygenase inhibitor users. Arch Otolaryngol 2007; 133: 28–31.
Lang S, Lauffer L, Clausen C, Lohr I, Schmitt B, Holzel D et al. Impaired monocyte function in cancer patients: restoration with a cyclooxygenase-2 inhibitor. FASEB J 2003; 17: 286–288.
Zhou W, Heist RS, Liu G, Asomaning K, Neuberg DS, Hollis BW et al. Circulating 25-hydroxyvitamin D levels predict survival in early-stage non-small-cell lung cancer patients. J Clin Oncol 2007; 25: 479–485.
Smolders J, Thewissen M, Damoiseaux J. Control of T cell activation by vitamin D. Nat Immunol 2011; 12: 3–4. 3 author reply.
Need AG, Nordin BE. Misconceptions — vitamin D insufficiency causes malabsorption of calcium. Bone 2008; 42: 1021–1024.
Weaver CM, McCabe LD, McCabe GP, Braun M, Martin BR, DiMeglio LA, Peacock M. Vitamin D status and calcium metabolism in adolescent black and white girls on a range of controlled calcium intakes. J Clin Endocrinol Metab 2008; 93: 3907–3914.
Abrams SA, Griffin IJ, Hawthorne KM, Gunn SK, Gundberg CM, Carpenter TO. Relationships among vitamin D levels, parathyroid hormone, and calcium absorption in young adolescents. J Clin Endocrinol Metab 2005; 90: 5576–5581.
Aloia JF, Chen DG, Yeh JK, Chen H. Serum vitamin D metabolites and intestinal calcium absorptionefficiency in women. Am J Clin Nutr 2010; 92: 835–840.
Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J et al. Vitamin D and calcium: a systematic review of health outcomes. Evidence Report No. 183. (Prepared by the Tufts Evidence-based Practice Center under Contract No. HHSA 290-2007-10055-I.). Rockville, MD:Agency for Healthcare Research and Quality; 2009.
Brot C, Jørgensen N, Madsen OR, Jensen LB, Sørensen OH. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 1999; 10: 509–516.
Apuhan T, Buğdaycı G, Alcelik A, Aktas G. Serum levels of vitamin D among patients with nasal polyps in Bolu, Turkey. J Aller Ther 2011; S5:1.
Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008; 168: 1629–1637.
MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985; 76: 1536–1538.
Ebeling PR, Sandgren ME, DiMagno EP, Lane AW, DeLuca HF, Riggs BL. Evidence of an age-related decrease in intestinal responsiveness to vitamin D: relationship between serum 1,25-dihydroxyvitamin D3 and intestinal vitamin D receptor concentrations in normal women. J Clin Endocrinol Metab 1992; 75: 176–182.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
About this article
Cite this article
Mostafa, B.ED., Abdelmageed, H.M., El-Begermy, M.M. et al. Value of vitamin D assessment in patients with head and neck squamous cell cancer before treatment. Egypt J Otolaryngol 32, 279–286 (2016). https://doi.org/10.4103/1012-5574.192550
- head and neck cancer
- squamous cell carcinoma
- vitamin D deficiency