Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck

Jalaly, Jalal B.; Hosseini, S. Mohsen; Shafique, Khurram; Baloch, Zubair W.

doi:10.1159/000496158

Cited by 26 publications

(39 citation statements)

References 51 publications

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“…In contrast to false negatives, false positive p16 staining in cellblocks appears to be much less of an issue, and none were noted in a recent literature review by Jalaly et al 22 Although we observed one false positive case in our study, on further investigation, the problem seemed to reside with false negative tissue staining, as confirmatory HPV DNA PCR studies performed on both cytological and surgical material were positive. The reason for the false negative tissue staining in this case remains elusive, but, given the somewhat pale appearance of the section, consideration is given to a pre-analytic issue with fixation or processing.…”

Section: Ta B L E 1 Patient Demographicscontrasting

confidence: 68%

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Correlation of p16 immunostaining in cell‐blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx

Song

Jalaly

2020

Cytopathology

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Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OPSCCs) represent a clinically and biologically distinct subset of head and neck squamous cell carcinomas (HNSCCs). Patients tend to be younger Caucasian men with no prior history of smoking or alcohol use. 1,2 Compared to their counterparts with non-HPV-related HNSCC, these patients also have a much better prognosis with improved responses to chemoradiation therapy and better overall and progression-free survival. 3,4 Given the prognostic implications of HPV status, early recognition of HPV-associated OPSCC is essential for proper management. It is thus recommended

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Section: Ta B L E 1 Patient Demographicscontrasting

confidence: 68%

“…12 We argued in a previous study and a recent literature review that the optimal cut-off may be in the range of 5%-15%. 19,22 While our current study was retrospective and not designed to determine the best p16 cut-off in cell-blocks, using a cut-off between 5%-15%…”

Section: Discussionmentioning

confidence: 99%

Correlation of p16 immunostaining in cell‐blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx

Song

Jalaly

2020

Cytopathology

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“…After Rb protein is degraded, cell cycle limitation is eliminated and transcription factor E2F is associated with increased p16 (INK4) protein expression. 7 HPV infection is closely related to p16 protein expression in OPSCC. Therefore, in these high-risk tumors, p16 can be used as a surrogate biomarker to detect the presence of HPV infection.…”

Section: Introductionmentioning

confidence: 99%

“…12 Then, p16 immunohistochemistry (IHC) in combination with HPV-DNA detection by PCR has been found to be a powerful indicator of clinical outcome in patients with OPSCC using univariate analysis. 7,13 And previous studies have indicated that p16 may enhance the immunogenicity of dendritic cells (DC) by means of Th1 cytokine secretion and cyclin-dependent pathways. 8 HPV infection can give rise to a very extensive of epithelial lesions.…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have indicated that regardless of the HPV infection status in the oropharynx, p16 protein can independently serve as a predictor of radiotherapy response. 6,7 Among patients undergoing surgery and postoperative adjuvant radiotherapy, the overall survival and disease-specific survival of patients with positive p16 protein were significantly longer than those with negative p16. 8 The results shown in our univariate analysis are consistent with it.…”

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confidence: 99%

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<p>The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study</p>

Meng

Yang

Liu

et al. 2020

PGPM

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Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

Ferrandino

Chen

Kappauf

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceThere is growing interest in the use of circulating plasma tumor human papillomavirus (HPV) DNA for diagnosis and surveillance of patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Recent advances in the assays, combining the identification of circulating HPV tumor DNA and tumor DNA fragment analysis (tumor tissue–modified viral [TTMV]-HPV DNA), have been shown to be highly accurate. However, use of these newer techniques has been limited to small cohort studies and clinical trials.ObjectiveTo establish the clinical efficacy of plasma TTMV-HPV DNA testing in the diagnosis and surveillance of HPV-associated OPSCC in a contemporary clinical setting.Design, Setting, and ParticipantsThis retrospective observational cohort study included patients with OPSCC who underwent TTMV-HPV DNA testing between April 2020 and September 2022 during the course of routine clinical care. For the diagnosis cohort, patients with at least 1 TTMV-HPV DNA measurement prior to initiation of primary therapy were included. Patients were included in the surveillance cohort if they had at least 1 TTMV-HPV DNA test performed after completion of definitive or salvage therapy.Main Outcomes and MeasuresPer-test performance metrics, including sensitivity, specificity, positive predictive value, and negative predictive value, for TTMV-HPV DNA testing.ResultsOf 399 patients included in the analysis, 163 were in the diagnostic cohort (median [IQR] age, 63 [56-68.5] years; 142 [87.1%] male), and 290 were in the surveillance cohort (median [IQR] age, 63 [57-70] years; 237 [81.7%] male). Of the 163 patients in the diagnostic cohort, 152 (93.3%) had HPV-associated OPSCC while 11 (6.7%) had HPV-negative OPSCC. The TTMV-HPV DNA sensitivity in pretreatment diagnosis was 91.5% (95% CI, 85.8%-95.4% [139 of 152 tests]), and the specificity was 100% (95% CI, 71.5%-100% [11 of 11 tests]). In the surveillance cohort, 591 tests conducted in 290 patients were evaluated. A total of 23 patients had molecularly confirmed pathologic recurrences. The TTMV-HPV DNA test demonstrated sensitivity of 88.4% (95% CI, 74.9%-96.1% [38 of 43 tests]) and specificity of 100% (95% CI, 99.3%-100% [548 of 548 tests]) in detecting the recurrences. Positive predictive value was 100% (95% CI, 90.7%-100% [38 of 38 tests]), and negative predictive value was 99.1% (95% CI, 97.9%-99.7% [548 of 553 tests]). The median (range) lead time from positive TTMV-HPV DNA test to pathologic confirmation was 47 (0-507) days.Conclusions and RelevanceThis cohort study demonstrated that when evaluated in a clinical setting, the TTMV-HPV DNA assay demonstrated 100% specificity in both diagnosis and surveillance. However, the sensitivity was 91.5% for the diagnosis cohort and 88.4% for the surveillance cohort, signifying that nearly 1 in 10 negative tests among patients with HPV-associated OPSCC was a false negative. Additional research is required to validate the assay’s performance and, if validated, then further research into the implementation of this assay into standard clinical practice guidelines will be required.

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Current Status of p16 Immunohistochemistry and HPV Testing in Fine Needle Aspiration Specimens of the Head and Neck

Cited by 26 publications

References 51 publications

Correlation of p16 immunostaining in cell‐blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx

Correlation of p16 immunostaining in cell‐blocks with corresponding tissue specimens for squamous cell carcinomas of the oropharynx

<p>The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study</p>

Performance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer

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