IMP3 and p16 expression in squamous cell carcinoma of the head and neck: A comparative immunohistochemical analysis

Abstract

Abstract. Expression of p16 has been established as a good surrogate marker for high-risk human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) patients, and it has been associated with an improved prognosis, irrespective of the actual HPV status. Conversely, the human insulin-like growth factor II mRNA binding protein 3 (IMP3) has been related to aggressiveness in several types of tumors. The aim of the present study was to investigate and compare p16 and IMP3 as markers of favorable and unfavorable behavior, respectively, in head and neck SCC (HNSCC), with particular reference to the HPV status. Both markers were analyzed by immunohistochemical analysis of 156 HNSCC samples originating from the oropharynx (n=81), oral cavity (n=44), larynx (n=15), hypopharynx (n=10) and nasopharynx (n=6). The HPV status was examined in a randomly selected representative subcohort (n=38) using polymerase chain reaction. Of the 156 HNSCC samples, 81 (51.9%) and 54 (34.6%) were positive for IMP3 and p16, respectively. IMP3 expression (P=0.022), p16 expression (P<0.001) and the combination of these markers (P<0.001) were significantly associated with tumor site. In particular, 69/81 (85%) OPSCC samples were positive for either one or both markers compared with 36/75 (48%) SCC samples from other sites. p16 expression was significantly associated with HPV infection (P= 0.017) and a trend towards a negative association between IMP3 expression and HPV infection was observed (P=0.053). The results of the present study suggested that IMP3 and p16 are more frequently expressed in OPSCC compared with other HNSCCs. The prognostic impact of IMP3 on OPSCC remains to be investigated in a larger series with an extended follow-up period. IntroductionSquamous cell carcinoma (SCC) is the leading cancer type affecting the head and neck region (HNSCC) representing >90% of malignant neoplasms of the oral cavity and oropharynx and 5 and 2% of all cancers in men and women, respectively (1). Tobacco smoking and alcohol consumption are the two major etiological factors of HNSCC and they work in a synergistic manner to initiate SCC (1). Approximately 75% of HNSCC cases in western countries are related to these two major risk factors, while the remainder is predominantly associated with viral infection, in particular infection with high-risk human papillomavirus (HPV) (1). HPV has been detected in a small fraction of oral cavity SCCs, and in 40-50% of oropharyngeal (mainly tonsillar) SCC (OPSCC) (1). While HPV-associated HNSCC may occur at any site, including the sinonasal tract, the majority of HPV-related SCCs originate in the lymphoid tissue bearing the oropharynx, mainly the palatine tonsil and the base of the tongue (1). Expression of p16 as a consequence of oncogenic HPV infection has been increasingly used as a surrogate marker for high-risk HPV infection, particularly in the female genital tract and the oropharynx (2,3). The sensitivity and specificity of p16 immunostaining for detecting high-risk HPV in OPSCC patie...

Diagnostic utility of high‐risk human papillomavirus mRNA in situ hybridisation in squamous cell carcinoma of unknown primary in the head and neck and implementing American Society of Clinical Oncology guideline recommendations

“…Another study also showed P16 positivity in 34.7% of the HNSCC cases. 33 Our study in concordance with several others shows that a small percentage of HPV-related HNSCC may exhibit patchy or less than 70% P16 expression on cell-blocks or small biopsies.…”

“…The manual platform used the RNA scope HPV-HR18 probe (Advanced Cell Diagnostics, Hayward, CA, USA), which recognises 18 HR-HPV genotypes (16,18,26,31,33,35,39,45…”

Comparative p16INK4A Expression in Laryngeal Carcinoma and Cervical Cancer Precursors: A Real-time Grid-based Immunocytochemistry Analysis

“…Based on our findings by applying DIA protocol for objective measurements regarding the corresponding expression levels, we observed that a significant proportion of the examined LSCCs demonstrated decreased p16 protein expression, associated with the smoking status of the patients and also with the p-stage of the malignancies. Interestingly, other studies focused on non-HPV-mediated LSCC cases have confirmed that abnormal expression of p16 is related with mutations in its gene locus on chromosome 9p (CDKN2A) (13,14). Larque et al have detected missense and frame-shift mutations in a series of LSCC patients examined by mRNA and IHC analyses (15).…”

The Impact of HPV DNA/p16 in Laryngeal/Hypopharyngeal Cancer: a Systematic Review and Meta-analysis

“…In addition, further research should be conducted to determine the optimal method of detecting p16 levels, as there is considerable variation in p16 expression patterns in LC and HPC reported in the published literature, which could be due to different detection methods and interpretation of results (15,31,46,47). Finally, given the lack of conclusive evidence on the prognostic significance of HPV status for patients with LC or HPC, it will be important to investigate other potential prognostic factors with more clinical utility.…”