Laryngeal squamous cell carcinoma (LSCC) represents the second most common malignancy in the head and neck worldwide. Traditionally, tobacco and alcohol exposure are the main risk factors for LSCC, however, molecular evidence has linked HPV, particularly HPV-16, in the pathogenesis of a subgroup of LSCC cases. The rate of HPV detection among LSCC samples has remained highly variable, ranging from 0% to 85%. This large variability is commonly related to: 1) differences in geographic region and ethnic group; 2) inadequate distinction of patients with LSCC from those with other cancers of the head and neck region such as oropharyngeal SCC; and 3) differences in sensitivity and specificity of HPV genotyping methods and diagnostic criteria.
A meta-analysis was recently conducted including 179 articles published between January 1964 and March 2015 reporting HPV detection in LSCC.
A sample size of 7,347 LSCCs was evaluated and the observed HPV prevalence was 25%. A variability in the prevalence of HPV in LSCC was observed according to 1) HPV detection method and 2) geographic origin. However, only the variability related to geographic area of the study reached statistical significance in stratified meta-analysis and when formal meta-regression was conducted, none of these characteristics were significant study-level covariates accounting for the heterogeneity of HPV prevalence. Noteworthy, the mere presence of HPV DNA in a tumor does not necessarily indicate that the virus is driving or contributing to tumor development or progression of LSCC. Although HR HPV can be found in LSCC, when using a rigorous definition of truly transcriptionally-active HPV-related, the rates are generally very low.
Despite the remarkable heterogeneity between methods for HPV status testing across the studies, variability on detection rates in LSCC seemed to be only explained by geographic origin, maybe reflecting genetic diversity or environmental and cultural differences. Noteworthy, these studies did not analyze the physical state or transcriptional activity of HPV in these tumors. Therefore, multicentric follow-up studies and functional studies are needed to further characterize the role of HPV in LSCC.