Prevalence of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma in the United States Across Time

Stein, Andrew P.; Saha, Sandeep; Yu, Menggang; Kimple, Randall J.; Lambert, Paul F.

doi:10.1021/tx500034c

Cited by 81 publications

(78 citation statements)

References 62 publications

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“…LSCC patients with an HPV-16 single infection most frequently present at an early stage (stage I-II) with advanced node status (N1-N2). Similar results were observed for patients with HNSCC and OPSCC [33,34]. In our study, 28 cases (21.2%) had multiple HPV infections.…”

Section: Tong Et Al: Prognostic Significance Of Hpc In Laryngeal Cancersupporting

confidence: 89%

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China

Tong

Geng

Yan

et al. 2018

Cell Physiol Biochem

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Background/Aims: Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. Here, we sought to evaluate the prevalence and genotype distribution of HPV in patients with laryngeal squamous cell carcinoma (LSCC) in northeast China. Methods: HPV DNA in specimens from 211 patients diagnosed with LSCC was analyzed by the polymerase chain reaction and in situ hybridization, and p16 overexpression was evaluated by immunohistochemistry. p16 expression was scored positive if strong and diffuse nuclear and cytoplasmic staining was present in >75% of tumor cells. Results: In this study, infection with HPV and p16 expression were not absolutely consistent. Among all patients, 132 (62.6%) were positive for HPV DNA (HPV+), while 23 (10.9%) were inconsistent for HPV and p16. Multivariate analysis indicated that HPV, but not p16, is an independent prognostic factor for overall survival in LSCC. Overall survival was significantly improved in HPV+ LSCC patients compared with the HPV-negative group (hazard ratio, 0.395; 95% confidence interval, 0.185-0.843; p = 0.016). Among the 132 HPV+ patients, 28 (21.2%) were HPV-16 single infection. Conclusion: This study indicates that HPV DNA is a more reliable surrogate marker than p16 for the prediction of survival in patients with LSCC.

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Section: Tong Et Al: Prognostic Significance Of Hpc In Laryngeal Cancersupporting

confidence: 89%

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China

Tong

Geng

Yan

et al. 2018

Cell Physiol Biochem

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“…In this study, we found an HPV prevalence of 24.3% in our cohort, which is lower than the prevalence in OSCC and tonsillar cancer reported for the USA (45-83%) 4,5 or northern Europe (26-93%), 5,23,24 but comparable to data for central Europe (14-33%) [25][26][27] . We considered HPV-association of samples when high risk HPV-DNA was detected along with p16INK4a expression.…”

Section: Discussioncontrasting

confidence: 64%

“…2,3 A recently published metaanalysis demonstrates a rising incidence of HPV1 OSCC in the United States from 21% (pre-1990), to 51% (1990-1999), to 65% (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013). 4 Patients with HPV-associated OSCC show lower levels of disease recurrence and progression compared to patients with HPV-negative OSCC. Even with good loco regional tumor control, patients with HPV-associated OSCC have similar rates of distant metastases as patients with HPVnegative OSCC.…”

mentioning

confidence: 97%

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

et al. 2016

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Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by beadbased hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD561) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p 5 0.004 and p 5 0.002). For the entire cohort presence of CD561 cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p 5 0.002; Cox regression: p 5 0.042). Presence of CD561 cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption 2 standard drinks per day (Kaplan-Meier: p 5 0.05 and p 5 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD561 cells and coexpression of CD16 and CD56 suggests that detected CD561 cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p 5 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.Head and neck cancer (HNC, comprising cancers of the oral cavity, lip, pharynx, nasopharynx and larynx) is ranking at position seven of newly diagnosed cancers and cause of cancer death worldwide, with 4.8% of total cancer incidence and 4.6% of total cancer mortality. 1 In particular oropharyngeal squamous cell carcinomas (OSCC) are related to high risk human papillomavirus (HPV) infection, which is accepted to be causally connected to HNC. 2,3 A recently published metaanalysis demonstrates a rising incidence of HPV1 OSCC in the United States from 21% (pre-1990), to 51% (1990-1999), to 65% (2000-2013). 4 Patients with HPV-associated OSCC show lower levels of disease recurrence and progression compared to patients with HPV-negative OSCC. Even with good loco regional tumor control, patients with HPV-associated OSCC have similar rates of distant metastases as patients with HPVnegative OSCC. Further efforts are needed to understand clinical and biological features of this distinct disease. 2,5,6 Molecular basis of HPV-associated cancers differ from their HPVunrelated counterparts. 3 Pathways related to cell cycle control or apoptosis (commonly affected by mutations in HPVnegative cancers) are silenced at protein level by HPVoncoproteins (mainly E6 and E7). It has been speculated that lower levels of genetic alterations contribute to better treat...

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“…All studies that tested for the presence of HPV in head and neck cancer tissues from patients diagnosed with squamous cell carcinoma of the head and neck (oral cavity, oropharynx, larynx and hypopharynx) were eligible for inclusion in this analysis. The bibliographies of several review articles were also examined in order to identify additional publications that might have been missed by our PubMed search (11)(12)(13)(14)(15). This review identified 291 original articles that qualified conditionally for the analysis.…”

Section: This Study Was Approved By the Fox Chase Cancer Center Instimentioning

confidence: 99%

Prevalence of HPV infection in racial–ethnic subgroups of head and neck cancer patients

et al. 2016

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The landscape of HPV infection in racial/ethnic subgroups of head and neck cancer (HNC) patients has not been evaluated carefully. In this study, a meta-analysis examined the prevalence of HPV in HNC patients of African ancestry. Additionally, a pooled analysis of subject-level data was also performed to investigate HPV prevalence and patterns of p16 (CDNK2A) expression amongst different racial groups. Eighteen publications (N = 798 Black HNC patients) were examined in the meta-analysis, and the pooled analysis included 29 datasets comprised of 3,129 HNC patients of diverse racial/ethnic background. The meta-analysis revealed that the prevalence of HPV16 was higher

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Prevalence of Human Papillomavirus in Oropharyngeal Squamous Cell Carcinoma in the United States Across Time

Cited by 81 publications

References 62 publications

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China

Prevalence and Prognostic Significance of HPV in Laryngeal Squamous Cell Carcinoma in Northeast China

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

Prevalence of HPV infection in racial–ethnic subgroups of head and neck cancer patients

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