Molecular identification and antifungal susceptibility testing of Candida species isolated from oral lesions in patients with head and neck cancer undergoing radiotherapy

Document Type : Original Articles


1 Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

2 Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran

3 Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Radiology and Radiation Therapy, School of Medicine, Babol University of Medical Sciences, Babol, Iran

5 Department of Radiation Oncology, School of Medicine, Imam Khomeini Hospital, Mazandaran University of Medical Science, Sari, Iran

6 Department of Microbiology, School of Veterinary Medicine, Islamic Azad University, Babol, Iran



Background and Purpose: Radiation therapy in patients with head and neck malignancies predisposes them to oral Candida colonization and infection due to damage of oral mucosa and destruction of the salivary gland. This study aimed to determine the prevalence of oropharyngeal candidiasis (OPC) in patients with head and neck cancer (HNC) undergoing radiotherapy (RT), identify the yeasts isolated from them, and determine their antifungal susceptibility.
Materials and Methods: This cross-sectional study was conducted from December 2018 to June 2019 at two referral radiotherapy centers in northern Iran. Yeast strains that were isolated from patients with HNC were identified using conventional and molecular methods. The in vitro activities of eight common antifungal drugs against 55 isolates were investigated according to the guidelines of the Clinical and Laboratory Standard Institute (M27-A3 and M27-S4) broth microdilution document.
Results: Among 59 patients receiving RT, the prevalence of OPC was 21 (35.59%) and 15 (25.42%) patients were diagnosed with colonization. The mean age of the patients was 55.32±13.3 years (within the range of 27-87 years). In this study, the pseudomembranous form was reported as the most clinical type of OPC. Candida albicans with the frequency of 60% was the most common type of Candida spp. that was observed in this study, although non-albicans Candida spp., such as C. glabrata (27.27%), C. tropicalis (5.45%), C. parapsilosis (3.63%), C. krusei (1.83%), and C. kefyr
(1.83%) were also isolated. Considering the low minimum inhibitory concentration range of amphotericin B, compared to fluconazole, administration of this agent is a more suitable antifungal drug for extensive oral candidiasis in these patients. Among azoles,clotrimazole had low efficacy and several studied isolates (65.5%) showed resistance.
Conclusion: Correct diagnosis as well as determining drug sensitivity and risk factors are the effective steps in reducing the complications related to oral candidiasis in people undergoing RT.


 1. Leung WK, Dassanayake RS, Yau JY, Jin LJ, Yam WC,
Samaranayake LP. Oral colonization, phenotypic, and genotypic
profiles of
Candida species in irradiated, dentate, xerostomic
nasopharyngeal carcinoma survivors. J Clin Microbiol. 2000;
2. Jham BC, Reis PM, Miranda EL, Lopes RC, Carvalho AL,
Scheper MA, et al. Oral health status of 207 head and neck
cancer patients before, during and after radiotherapy. Clin Oral
Investig. 2008; 12(1):19-24.
3. Al-Abeid HM, Abu-Elteen KH, Elkarmi AZ, Hamad MA.
Isolation and characterization of
Candida spp. in Jordanian
cancer patients: prevalence, pathogenic determinants, and
antifungal sensitivity. Jpn J Infect Dis. 2004; 57(6):279-84.
4. Rad M, Ayatollahi MS, Kakoei S, Bahador M, Borna R,
Lashkarizadeh N. Oropharyngeal candidiasis and resistance to
antifungal drugs in patients receiving radiation for head and neck
cancer. J Oral Health Oral Epidemiol. 2012; 1(1):36-40.
5. Kauffman CA, Pappas PG, Sobel JD, Dismukes WE. Essentials
of clinical mycology. New York: Springer; 2011.
6. Parker JN, Parker PM. The official patient's source ebook on
Oropharyngeal Candidiasis. London: ICON Health Publications;
7. Dismukes WE, Pappas PG, Sobel JD. Clinical mycology.
Oxford: Oxford University Press; 2003.
8. Redding SW, Dahiya MC, Kirkpatrick WR, Coco BJ, Patterson
TF, Fothergill AW, et al.
Candida glabrata is an emerging cause
of oropharyngeal candidiasis in patients receiving radiation for
head and neck cancer. Oral Surg Oral Med Oral Pathol Oral
Radiol Endodontol. 2004; 97(1):47-52.
9. Bensadoun RJ, Patton LL, Lalla RV, Epstein JB. Oropharyngeal
candidiasis in head and neck cancer patients treated with radiation:
update 2011. Support Care Cancer. 2011; 19(6):737-44.
10. Jain M, Shah R, Chandolia B, Mathur A, Chauhan Y, Chawda J,
et al. The oral carriage of
Candida in oral cancer patients of
Indian origin undergoing radiotherapy and/or chemotherapy. J
Clin Diagno Res. 2016; 10(2):ZC17-20.
11. Jahanshiri Z, Manifar S, Moosa H, Asghari-Paskiabi F,
Mahmoodzadeh H, Shams-Ghahfarokhi M, et al. Oropharyngeal
candidiasis in head and neck cancer patients in Iran: species
identification, antifungal susceptibility and pathogenic
characterization. J Mycol Med. 2018; 28(2):361-6.
12. Singh GK, Capoor MR, Nair D, Bhowmik K. Spectrum of
fungal infection in head and neck cancer patients on
chemoradiotherapy. J Egypt Natl Cancer Inst. 2017; 29(1):33-7.
13. Anaissie EJ, McGinnis MR, Pfaller MA. Clinical mycology.
New York: Elsevier Health Sciences; 2009.
14. Snydman DR. Shifting patterns in the epidemiology of
Candida infections. Chest. 2003; 123(5 Suppl):
15. Sobel JD. The emergence of non-albicans
Candida species as
causes of invasive candidiasis and candidemia. Curr Infect Dis
Rep. 2006; 8(6):427-33.
16. Pfaller M, Diekema D, Messer S, Boyken L, Hollis R. Activities
of fluconazole and voriconazole against 1,586 recent clinical
isolates of
Candida species determined by broth microdilution,
disk diffusion, and Etest methods: report from the ARTEMIS
Global Antifungal Susceptibility Program, 2001. J Clin
Microbiol. 2003; 41(4):1440-6.
17. Greene JC, Vermillion JR. The simplified oral hygiene index. J
Am Dent Assoc. 1964; 68:7-13.
18. Lau AF, Kabir M, Chen SC, Playford EG, Marriott DJ, Jones M,
et al.
Candida colonization as a risk marker for invasive
candidiasis in mixed medical-surgical intensive care units:
development and evaluation of a simple, standard protocol. J
Clin Microbiol. 2015; 53(4):1324-30.
19. Shokohi T, Soteh MH, Pouri ZS, Hedayati M, Mayahi S.
Identification of
Candida species using PCR-RFLP in cancer
patients in Iran. Indian J Med Microbiol. 2010; 28(2):147-51.
20. Ghannoum M. Reference Method for Broth Dilution Antifungal
Susceptibility Test of Yeast M27-S4. Wayne, PA: Clinical and
Laboratory Standards Institute; 2012.
21. Silverman Jr S, Luangjarmekorn L, Greenspan D. Occurrence of
Candida in irradiated head and neck cancer patients. J Oral
Med. 1984; 39(4):194-6.
22. Dahiya MC, Redding SW, Dahiya RS, Eng TY, Kirkpatrick
WR, Coco BJ, et al. Oropharyngeal candidiasis caused by nonalbicans yeast in patients receiving external beam radiotherapy
for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2003;
23. Nicolatou
Galitis O, Dardoufas K, Markoulatos P,
Lontou A, Kyprianou K, Kolitsi G, et al. Oral
pseudomembranous candidiasis, herpes simplex virus
infection, and oral mucositis in head and neck cancer patients
receiving radiotherapy and granulocyte
macrophage colony
stimulating factor (GMCSF) mouthwash. J Oral Pathol Med.
2001; 30(8):471-80.
24. Epstein JB, Freilich MM, Le ND. Risk factors for oropharyngeal
candidiasis in patients who receive radiation therapy for
malignant conditions of the head and neck. Oral Surg Oral Med
Oral Pathol. 1993; 76(2):169-74.
25. Bashir H, Ahmad J. Oral
Candida colonization and infection in
cancer patients and their antifungal susceptibility in a tertiary
care hospital. Int J Adv Res. 2014; 2:541-50.
26. Samaranayake LP. Oral mycoses in HIV infection. Oral Surg
Oral Med Oral Pathol. 1992; 73(2):171-80.
27. Thaweboon S, Thaweboon B, Srithavaj T, Choonharuangdej S.
Oral colonization of
Candida species in patients receiving
radiotherapy in the head and neck area. Quintessence Int. 2008;
28. Mirhendi H, Makimura K, Khoramizadeh M, Yamaguchi H. A
one-enzyme PCR-RFLP assay for identification of six medically
Candida species. Nihon Ishinkin Gakkai Zasshi. 2006;
29. Yogitha P, Lakshmi N, Lakshmi KR, Krishna PB, Cheemala SS.
Isolation and speciation of genus candida in patients undergoing
chemotherapy and radiotherapy for head and neck tumours. Int J
Res Med Sci. 2015; 3(5):1189-94.
30. Aslani N, Janbabaei G, Abastabar M, Meis JF, Babaeian M,
Khodavaisy S, et al. Identification of uncommon oral yeasts
  from cancer patients by MALDI-TOF mass spectrometry. BMC
Infect Dis. 2018; 18(1):24.
31. Mann PA, McNicholas PM, Chau AS, Patel R, Mendrick C,
Ullmann AJ, et al. Impact of antifungal prophylaxis on
colonization and azole susceptibility of
Candida species.
Antimicrob Agents Chemother. 2009; 53(12):5026-34.
32. Sweeney M, Bagg J, Baxter W, Aitchison T. Oral disease in
terminally ill cancer patients with xerostomia. Oral Oncol. 1998;
33. Bashir H, Ahmad J. Oral
Candida colonization and infection in
cancer patients and their antifungal susceptibility in a tertiary
care hospital. Int J Adv Res. 2014; 2:541-50.
34. Katiraee F, Teifoori F, Soltani M. Emergence of azole-resistant
Candida species in AIDS patients with oropharyngeal
candidiasis in Iran. Curr Med Mycol. 2015; 1(3):11-6.
35. Jayachandran AL, Katragadda R, Thyagarajan R, Vajravelu L,
Manikesi S, Kaliappan S, et al. Oral Candidiasis among cancer
patients attending a tertiary care hospital in Chennai, South
India: an evaluation of Clinicomycological association and
antifungal susceptibility pattern. Can J Infect Dis Med
Microbiol. 2016; 2016:8758461.
36. Mohamadi J, Motaghi M. Anti-fungal resistance in candida
isolated from oral and diaper rash candidiasis in neonates.
Bioinformation. 2014; 10(11):667-70.
37. Zida A, Yacouba A, Bamba S, Sangare I, Sawadogo M,
Guiguemde T, et al. In vitro susceptibility of
Candida albicans
clinical isolates to eight antifungal agents in Ouagadougou
(Burkina Faso). J Mycol Med. 2017; 27(4):469-75.
38. Mulu A, Kassu A, Anagaw B, Moges B, Gelaw A, Alemayehu
M, et al. Frequent detection of ‘azole’resistant
Candida species
among late presenting AIDS patients in northwest Ethiopia.
BMC Infect Dis. 2013; 13(1):82.
Volume 7, Issue 1
March 2021
Pages 44-50
  • Receive Date: 17 February 2021
  • Revise Date: 30 April 2021
  • Accept Date: 02 May 2021
  • First Publish Date: 02 May 2021