Prognostic utility of HPV specific testing in addition to p16 immunohistochemistry in oropharyngeal squamous cell carcinoma

Sathasivam, Hans Prakash; Santambrogio, Alice; Andoniadou, Cynthia L.; Robinson, Max; Thavaraj, Selvam

doi:10.1093/annonc/mdy313

Cited by 10 publications

(17 citation statements)

References 5 publications

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“…Manual RNA ISH testing of HPV DNA ISH negative cases has been shown to identify these false‐negative results. In the current study, we validated a novel automated clinical diagnostic platform against a sub‐cohort previously subjected to manual RNA ISH testing and showed a strong correlation between automated and manual methods ( κ = .815) 21 . The platform utilized in our study is already in routine use within the diagnostic pathology laboratory setting.…”

Section: Discussionmentioning

confidence: 66%

“…Therefore, the HPV status of these OpSCCs remains ambiguous. We, and others, have shown previously that p16+DNAISH− OpSCCs have poorer clinical outcomes than those in which DNA ISH is positive 21,23‐25 . Manual RNA ISH testing of HPV DNA ISH negative cases has been shown to identify these false‐negative results.…”

Section: Discussionmentioning

confidence: 89%

“…OpSCCs have poorer clinical outcomes than those in which DNA ISH is positive. 21,[23][24][25] Manual RNA ISH testing of HPV DNA ISH negative cases has been shown to identify these false-negative results. In the current study, we validated a novel automated clinical diagnostic platform against a sub-cohort previously subjected to manual RNA ISH testing and showed a strong correlation between automated and manual methods (κ = .815).…”

Section: Discussionmentioning

confidence: 99%

“…Of these, there were 38 cases that had been assessed as positive for p16 and DNA ISH (p16+DNA+) and 42 cases negative for p16 (p16−). In addition, 20 p16 positive but DNA ISH negative (p16+DNA−) cases (of which 15 had previously undergone manual RNA ISH testing as part of a prior study) were included 21 …”

Section: Methodsmentioning

confidence: 99%

“…In addition, 20 p16 positive but DNA ISH negative (p16+DNA−) cases (of which 15 had previously undergone manual RNA ISH testing as part of a prior study) were included. 21…”

Section: Case Selectionmentioning

confidence: 99%

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RNA in situ hybridization for human papillomavirus testing in oropharyngeal squamous cell carcinoma on a routine clinical diagnostic platform

Henley-Smith

Santambrogio

Andoniadou

et al. 2020

J Oral Pathology Medicine

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Background The current diagnostic standard for detection of high‐risk human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma is via a two‐stage algorithm, namely p16 immunohistochemistry followed by HPV DNA in situ hybridization in p16 positive cases. This study evaluated the feasibility of automated RNA in situ hybridization on a clinical platform as a single‐step alternative to the two‐stage algorithm within a routine diagnostic histopathology setting. Methods Thirty‐eight cases positive for both p16 and DNA in situ hybridization, 42 p16 negative cases and 20 cases positive for p16 but negative for DNA in situ hybridization were randomly selected. High‐risk HPV RNA in situ hybridization was undertaken on all cases on an automated clinical platform. Manufacturer‐recommended and on‐slide additional p16/HPV positive and negative controls were used. Test quality assurance and diagnostic RNA in situ hybridization were independently assessed by two observers. A consensus diagnosis was reached in the presence of a third observer on discordant cases. All RNA in situ hybridization results were then correlated against p16 and DNA ISH status. Results Inter‐slide RNA in situ hybridization staining variation was observed in control sections. RNA in situ hybridization demonstrated a high inter‐observer agreement rate (κ = .897, P < .001). Following consensus review, there was full concordance between RNA in situ hybridization and the current standard. Conclusion Human papillomavirus testing by standalone automated RNA in situ hybridization on a clinical diagnostic platform currently available in routine diagnostic histopathology laboratories is a feasible alternative to the two‐step algorithm of p16 and DNA in situ hybridization. Control tissue staining procedures need to be adapted to achieve the most accurate results.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…In addition, 20 p16 positive but DNA ISH negative (p16+DNA−) cases (of which 15 had previously undergone manual RNA ISH testing as part of a prior study) were included. 21…”

Section: Case Selectionmentioning

confidence: 99%

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RNA in situ hybridization for human papillomavirus testing in oropharyngeal squamous cell carcinoma on a routine clinical diagnostic platform

Henley-Smith

Santambrogio

Andoniadou

et al. 2020

J Oral Pathology Medicine

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Correlation of transcriptionally active human papillomavirus status with the clinical and molecular profiles of head and neck squamous cell carcinomas

et al. 2021

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Background To examine the molecular profiles of human papillomavirus (HPV)‐positive and HPV‐negative head and neck squamous cell carcinomas (HNSCCs), expression of epidermal growth factor receptor (EGFR), phospho‐EGFR dimers, hypoxia markers, and cancer stem cell markers were evaluated. Methods HPV‐status was confirmed using RNA‐ISH. Immunohistochemical data of biomarker expression levels were analyzed using the Mann‐Whitney U test. The clinical outcomes and biomarker expression in the HPV‐positive (n = 25), matched HPV‐negative (n = 49), and p16‐positive/HPV‐negative (n = 20) subgroups were comparatively analyzed. Results HPV was detected in 25 (5.8%) cases and was significantly associated with favorable outcomes. HPV‐positive tumors exhibited lower membrane expression of EGFR, pEGFRY1068, pEGFRY1173, CD44, CD44v6, and CD98hc than HPV‐negative and p16‐positive tumors. The expression of HIF1α, CA9, ALDH1A1, and SOX2 was not significantly associated with HPV‐status. The clinical outcomes and biomarker expression levels were similar between the HPV‐negative and p16‐positive HNSCC. Conclusion HPV‐positive HNSCC exhibited distinct molecular profile compared to HPV‐negative and p16‐positive HNSCC. The clinical and molecular profiles were similar between p16‐positive and HPV‐negative subgroups.

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p16 in highly malignant esophageal carcinomas: the correlation with clinicopathological factors and human papillomavirus infection

et al. 2020

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Abstractp16 is generally considered to be a surrogate maker of human papillomavirus (HPV) infection and also a predictive marker of favorable clinical outcome of patients with squamous cell carcinoma of the oropharynx. p16 overexpression is also known to be induced by deregulation of RB1 in neuroendocrine carcinomas. In highly malignant esophageal neoplasms, however, the status of p16 has remained largely unknown. We immunolocalized p16 and Rb1 in 82 surgically resected esophageal high-grade squamous cell carcinomas (46 poorly differentiated and 36 basaloid squamous cell carcinomas) and 15 esophageal small-cell carcinomas in order to clarify the clinical and biological significance of p16. p16 immunoreactivity was detected in 7/82 (9%) high-grade squamous cell carcinomas and 15 (100%) small-cell carcinomas. p16 immunoreactivity was significantly associated with Rb1 protein loss in both groups (P < 0.001). HPV was detected in none of the p16-positive cases examined. Clinical outcome of the p16-positive high-grade squamous cell carcinomas was not different from that of the p16-negative counterparts (P = 0.687) but significantly better than those with the small-cell carcinomas (P = 0.023). p16 was therefore considered to be induced through an inactivation of the RB1 signaling pathway and not through HPV infection in highly malignant esophageal neoplasms. Nevertheless, patients’ clinical outcome of these neoplasms significantly differs; therefore, small-cell carcinomas have to be carefully differentiated from other neoplasms. In addition, p16 overexpression is not predictive of favorable clinical outcome in high-grade squamous cell carcinomas of the esophagus.

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Prognostic utility of HPV specific testing in addition to p16 immunohistochemistry in oropharyngeal squamous cell carcinoma

Cited by 10 publications

References 5 publications

RNA in situ hybridization for human papillomavirus testing in oropharyngeal squamous cell carcinoma on a routine clinical diagnostic platform

RNA in situ hybridization for human papillomavirus testing in oropharyngeal squamous cell carcinoma on a routine clinical diagnostic platform

Correlation of transcriptionally active human papillomavirus status with the clinical and molecular profiles of head and neck squamous cell carcinomas

p16 in highly malignant esophageal carcinomas: the correlation with clinicopathological factors and human papillomavirus infection

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