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.