Introduction
Although new treatment protocols for head and neck cancer have been developed in recent years, head and neck cancer is still the sixth most common cancer worldwide, mainly due to its association with human papillomavirus (HPV) and tobacco and alcohol usage (1) . The most common histopathological type is squamous cell carcinoma (SCC) and the oral cavity, larynx, and pharynx are most frequently involved (2) .
Laryngeal SCC is the most common head and neck cancer, affecting an estimated 100,000 people per year (3). For patients who present with advanced disease, the mainstay of treatment is total laryngectomy with or without adjuvant therapy (4) . However, the survival rate is low. Among laryngeal cancers, glottic carcinomas are the most common subgroup, with the glottis being involved approximately 3 times more often than the supraglottic larynx. Glottic cancers are usually diagnosed in the early stage due to symptoms of hoarseness.
In early glottic cancer, lymph node metastasis is rarely seen, with an incidence of clinically positive lymph nodes of nearly zero for stage T1 and < 2% for stage T2 disease, and a complete cure can often be achieved by radiotherapy (RT) or surgery (5-7). Therefore, the goal is to achieve the best local control leading to a complete cure and optimal functional results. At present, there are various treatment modalities for treating early glottic cancer; namely, RT or partial laryngectomy techniques. Although surgery has been used for decades, its use has greatly decreased in recent years because of declining functional results and advances in RT (8). The optimal treatment for early glottic cancer has remained an issue of debate, primarily due to a lack of evidence from large prospective randomized trials (9). Recent studies have shown similar local control between RT and surgery. Mendenhall et al. reported local control rates ranging from approximately 80% to 94% for T1 tumors and 70% to 85% for T2 tumors with both modalities (10,11).
Several prognostic factors can be used for the evaluation of laryngeal cancer. Microscopic grade is an independent prognostic factor and correlates with clinical stage (12). Recurrence is related to aneuploidy (13). The presence of S100-positive Langerhans cells around the tumor is called host reaction and has been associated with favorable prognosis (14).
The most accepted prognostic factors are TNM classification. However, the TNM system cannot distinguish aggressive tumors from nonaggressive tumors of the same size. Identifying one or more biomarkers to predict the biological behavior of head and neck squamous cell carcinomas (HNSCCs) would be beneficial. Recently, a small population of cancer cells referred to as cancer stem cells (CSCs) was found to be responsible for tumor initiation, relapse, and resistance to chemotherapy or RT; therefore, eradicating CSCs is considered critical in cancer therapy (15,16). The CSC hypothesis has also been proposed for HNSCCs; some cell surface markers have been reported as CSC markers in HNSCC, such as CD44, CD133, ALDH1, and ABCG2 (17-19), and high expression of these markers is usually regarded as an indicator of poor prognosis. Among them, CD44 is the most reported CSC marker in HNSCC (20-22).
In this study, we aimed to evaluate of the predictive value of CD44 and ALDH1 expression for prognosis and treatment response in patients with early-stage laryngeal cancer receiving RT.