Materials and Methods Unstimulated whole-mouth saliva was collected from 45 cancer patients (1 week before treatment, during the treatment, and 1 week after completion of radiotherapy) and from 20 controls. BPIFA1 and BPIFA2 expression was detected by western blotting and analyzed along with clinicopathologic data and side effects from the radiotherapy.Results A facial radiation field was associated with lower salivary flow during and after radiotherapy and correlated with side effects, mainly mucositis. Salivary BPIFA1 expression levels were similar between the control group and the patient group before treatment. On the other hand, BPIFA2 levels were higher in the patient group before treatment compared with the control group. BPIFA concentration was modified by radiotherapy as BPIFA1 levels increased (P =.0081) and BPIFA2 decreased (P <.0001). Higher levels of BPIFA1 were associated with the presence of mucositis (P =.0363) and its severity (P =.0500).Conclusions The present study found that levels of BPIFA1 and glycosylated forms of BPIFA2 are affected by radiotherapy, suggesting that these proteins may play a role in the oral microenvironment in irradiated patients with head and neck cancer.Objective To determine the effects of radiotherapy on salivary BPIFA expression and to investigate the role of BPIFA in the development of known radiotherapy side effects.11914858Siegel, R., Ma, J., Zou, Z., Jemal, A., Cancer statistics, 2014 (2014) CA Cancer J Clin, 64, pp. 9-29Bhide, S.A., Newbold, K.L., Harrington, K.J., Nutting, C.M., Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers (2012) Br J Radiol, 85, pp. 487-494Bourhis, J., Etessami, A., Lusinchi, A., New trends in radiotherapy for head and neck cancer (2005) Ann Oncol, 16, pp. 255-ii257Specht, L., Oral complications in the head and neck radiation patient. 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