Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis

Abstract

BackgroundHuman papillomavirus (HPV)-related tonsillar squamous cell carcinoma (TSCC) has recently been characterized as a distinct subset with a favorable prognosis. The prevalence and clinicopathologic significance of HPV-related TSCC in Koreans are not well known.MethodsHPV in situ hybridization (ISH) accompanied by p53, p16, pRb, and cyclin D1 immunohistochemical staining were performed on 89 resection cases of TSCC from 2000 through 2010.ResultsHPV was detected by ISH in 59 of 89 cases (66.3%). HPV-positive TSCCs were more common in younger ages (p=0.005), and tumor sizes were smaller in the HPV-positive compared to the HPV-negative group (p=0.040). Positive HPV staining was significantly correlated with p16 expression (p<0.001), pRb inactivation (p=0.003), and cyclin D1 down-regulation (p<0.001) but not with p53 expression (p=0.334). Seventeen cases that showed p16-immunopositivity with HPV-negativity by ISH were retested by HPV typing; HPV DNA was not detected in all cases. There was no significant difference between HPV-positive and HPV-negative patients either in the disease-specific survival (DSS, p=0.857) or overall survival (p=0.910). Furthermore, pRb-inactivated cases showed better DSS (p=0.023), and p53-positive cases showed worse DSS (p=0.001).ConclusionsAlthough high HPV prevalence was noted, it was not correlated with histopathologic findings or survival benefit. In addition to p53 expression, pRb inactivation along with p16 overexpression and down-regulation of cyclin D1 are thought to be important pathogenetic steps for developing TSCCs.

Prevalence of high-risk human papillomavirus and its genotype distribution in head and neck squamous cell carcinomas

“…On the other hand, rates at 20%–30% level in four studies [ 18 , 19 , 22 , 28 ] were far lower compared with the others at 70% level. Another four studies of tonsillar or oropharyngeal SCCs documented p16 IHC results without performing HPV-specific tests; the p16-positive rates were all greater than 50%, from 62.0% to 82.5% [ 16 , 20 , 26 , 29 ]. For other HN subsites, reports of HR HPV prevalence were found for oral cavity and hypopharyngeal carcinomas ( Table 3 ).…”

“…As for the Republic of Korea, a National Health Insurance Service data-based study reported an increase in the incidence of tonsillar cancer during 2002-2015 from 1.1 to 2.4 for men, and from 0.31 to 0.46 for women (per 100,000) [13]. On the other hand, data on HPV-positive fraction of Korean HN SCCs has been published for small cohorts of oropharynx and oral cavity tumors, with a wide range of values [14][15][16][17][18][19][20][21][22][23][24]. Using a recent (2011-2019) and large (n = 466) HN SCC dataset and employing HPV DNA polymerase chain reaction (PCR), we aimed to assess the HPV-attributable fraction in each subsite of the oropharynx, oral cavity, larynx, hypopharynx, and sinonasal tract.…”

Association Between Fibroblast Growth Factor Receptor 1 Gene Amplification and Human Papillomavirus Prevalence in Tonsillar Squamous Cell Carcinoma With Clinicopathologic Analysis

“…We used the previously published tissue microarray (TMA). 13 Briefly, TMAs were constructed from 2-mm cores of representative tumor areas from paraffin-embedded blocks, in duplicate. TMAs were used in immunohistochemical staining of p16 and FGFR1, fluorescence in situ hybridization (FISH) for FGFR1 gene amplification, and HPV in situ hybridization (HPV ISH).…”

“…1. This study cohort was previously published by Lee et al 13 The study was approved by the Institutional Review Board of Asan Medical Center. Smoking history was measured in pack-years and classified into three categories: nonsmoker, former smoker who quit smoking more than 10 years ago, or current smoker.…”

“…We used partly previously published data 13 of HPV ISH, p16, and HPV genotyping. Fifty-nine of 89 (66.3%) TSCC patients showed HPV ISH positivity, and 74 of 89 (83.1%) TSCCs showed p16 immunopositivity ( Supplementary Figure 1).…”