Introduction
Laryngeal squamous cell carcinoma (LSCC) originates from the mucosal
epithelium of the larynx and is among the most frequently occurring
malignancies in the head and neck region. Unfortunately, the incidence
of LSCC, along with other head and neck SCCs, has been steadily
increasing. According to GLOBACAN, the Global Cancer Observatory, there
is an anticipated 30% rise in the number of cancer cases by the year
2030 (1). This rise may be due to several factors, including a lack of
concrete screening strategies, carcinogen consumption, and increased
human papillomavirus (HPV) infections (2). Despite the increase in
cases, the survival rate of LSCCs has not significantly decreased over
the past few decades. On average, the 5-year survival rate is about
40-60%, regardless of the patient’s age or anatomical site of the tumor
(3). Interestingly, some studies suggest that the slight improvement in
survival is more related to the rise of patients with HPV-associated
LSCC, which has a better overall outcome than actual advances in cancer
control (2).
The prognostic factors of LSCC are typically grouped into three
categories: host, tumor, and treatment, which encompass various elements
such as age, gender, nutritional or performance status, tumor site,
tumor histological grading, perineural/vascular invasion, and TNM
staging (4). Despite this, studies have shown conflicting results
regarding their accuracy in predicting patient outcomes (5). As a
result, there is currently no definitive predictor of survival due to
the primary tumor site’s heterogeneity, tumor behavior, and molecular
mechanisms (6). For this reason, quests for discovering a more reliable
prognostic parameter have been carried out.
When predicting tumor behavior and assessing its aggressiveness, it is
important to consider the histopathologic findings. Tumor progression
and response to treatment are also closely linked to how tumor cells
interact with the microenvironment around them (7). Studies have shown
that cancer cells at the tumor front tend to be more aggressive and
contribute to tumor growth (8). Peritumoral tumor budding (TB) occurs
when small clusters of non-glandular cancer cells appear throughout the
invasive tumor front. This is associated with decreased cell adhesion
and increased local invasion (9). While TB is commonly reported in
colorectal cancers, it is now recognized as a reliable predictor of
lymph node metastasis, advanced cancer prognosis, and response to
therapy in multiple malignancies such as lung SCC, esophageal SCC,
breast cancer, and pancreatic ductal adenocarcinoma (10, 11). The TBNS
(tumor budding/nest size) grading system, which combines TB with cell
nest size (CNS), is also considered a practical prognostic element in
SCCs of various sites, including lung, oral cavity, larynx, and
hypopharynx (12, 13). The adverse effect of TB on survival of LSCC, even
in patients with a lower TNM staging score, have also been confirmed in
previous studies (14-16). Despite the significant impact TB can have on
patient survival, it has yet to be included in standard pathology
reports for LSCC due to limited data and a lack of systematic scoring
systems.
Hence, through this study, we aim to investigate the relationship of TB
and CNS with nodal involvement and overall prognosis in patients with
laryngeal SCCs to further establish the value of TB and CNS as an
inexpensive, easily assessable, yet highly reliable prognostic factor.