Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population‐based study

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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“…4). This was consist with many studies showing that HPV RNA+ was the main factor for prognosis [37].…”

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

confidence: 83%

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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“…Therefore, Garnaes et al. subclassified TSCC into specified TSCC (STSCC) and nonspecified TSCC (NSTCC), with HPV significantly more prevalent in STSCC than in NSTSCC and with a more pronounced correlation between survival and HPV in the latter . Here, we aimed to examine the histopathological impact on HPV status prevalence and survival in TSCC in a separate cohort of TSCC patients diagnosed 1970–2002 in Stockholm.…”

Section: Introductionmentioning

confidence: 97%

Human papillomavirus and survival of patients per histological subsite of tonsillar squamous cell carcinoma

Haeggblom

Attoff

Hammarstedt‐Nordenvall

et al. 2018

Cancer Medicine

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Current data advocate that oropharyngeal squamous cell carcinoma (OPSCC) should be divided into subsites when evaluating the presence of human papillomavirus (HPV) and prognosis. More specifically, tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) have much higher HPV prevalence compared to other OPSCC. Moreover, patients with HPV positive (HPV+) TSCC and BOTSCC have a better prognosis as compared to patients with HPV negative (HPV−) corresponding tumors, while the prognostic role of HPV in other OPSCC is unclear. Furthermore, in a recent report from Denmark, TSCC was further subclassified into specified TSCC (STSCC) and nonspecified TSCC (NSTSCC), with HPV significantly more prevalent in STSCC. In this study, the histopathological influence of HPV prevalence and survival in TSCC was analyzed in a TSCC cohort with known HPV status, of patients diagnosed 1970–2002 in Stockholm. In total, 139 TSCC biopsies with both tumor and adjacent normal tissue were separated into STSCC and NSTSCC. HPV was significantly more commonly found in STSCC than in NSTSCC. Patients with HPV+ STSCC had a better disease‐specific and overall survival as compared to patients with HPV+ NSTSCC, but no survival differences were observed in patients with HPV− STSCC and NSTCC. These findings confirm previous reports and suggest that TSCC subsite may also be of relevance for clinical outcome and should be further followed up in future studies.

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“…Third, the small sample size, limited number of outcome events, and short follow-up time might cause chance findings. Finally, some HPV16-positive SCCOP may be negative for p16 expression, It is likely that the some HPV16-positive SCCOP that failed to express p16 was not driven by HPV, but HPV was just an incidental bystander in that tumor 43 . This discordance could occur between HPV status and p16 expression since some events (e.g., mutation, deletion, other epigenetic changes, etc) may impact the p16, leading to biased estimation of the associations.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in microRNA‐binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx

Zhu

Zhang

et al. 2017

Intl Journal of Cancer

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The incidence of squamous cell carcinoma of the oropharynx (SCCOP) continues to rise because of increasing rates of human papillomavirus (HPV) infection. Inherited polymorphisms in DNA repair pathways may influence the risk of SCCOP development and the prognosis of SCCOP. We sought to determine whether polymorphisms in microRNA (miRNA)-binding sites within 3' -untranslated regions (3’UTRs) of genes in DNA repair pathways modulate the risk of SCCOP recurrence. We evaluated the associations between nine such polymorphisms and SCCOP recurrence in 1008 patients with incident SCCOP using the log-rank test and multivariable Cox models. In an analysis of all the patients, patients with variant genotypes of BRCA1 rs12516 and RAD51 rs7180135 had better disease-free survival (log-rank, P = 0.0002 and P = 0.0003, respectively) and lower risk of SCCOP recurrence (hazard ratio [HR], 0.5, 95% confidence interval [CI], 0.2-0.8, and HR, 0.5, 95% CI, 0.3-0.9, respectively) than patients with common homozygous genotypes of the two polymorphisms after multivariable adjustment. Moreover, in tumor HPV16-positive patients, patients with variant genotypes of the same two polymorphisms also had better disease-free survival (log-rank, P = 0.004 and P = 0.003, respectively) and lower recurrence risk (HR, 0.2, 95% CI, 0.1-0.6, and HR, 0.2, 95% CI, 0.0-0.7, respectively) than patients with common homozygous genotypes of the two polymorphisms. No such significant associations were found for other polymorphisms. These findings support significant roles of BRCA1 rs12516 and RAD51 rs7180135 in modifying the risk of recurrence of SCCOP, particularly HPV16-positive SCCOP. However, these results must be validated in larger studies.

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Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication: Insights from a large population‐based study

Cited by 58 publications

References 27 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

Human papillomavirus and survival of patients per histological subsite of tonsillar squamous cell carcinoma

Genetic variants in microRNA‐binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx

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