p16 Immunohistochemistry Is a Useful Diagnostic Adjunct in Cases of Metastatic Cervical Carcinoma of Unknown Origin

Rohrbach, Marc R.; Britt, Christopher J.; Schwalbe, Michael; Wieland, Aaron M.; Hartig, Gregory K.

doi:10.1016/j.joms.2016.08.029

Cited by 3 publications

(4 citation statements)

References 9 publications

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“…Direct testing for HPV-DNA by polymerase chain reaction (PCR) or in situ hybridization has been assessed with findings favoring the first one for higher sensitivity and lower cost. 17,52,[58][59][60][61][62][63] However, p16 is also strongly expressed in a subset of aggressive, lymph-node positive, cutaneous squamous carcinoma of the head and neck as well as benign branchial cysts. 56 Serum antibodies against E6 and E7 have also shown diagnostic utility, with 91% sensitivity and 100% specificity in HPV-related SCCUP.…”

Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

“…55 It has been correlated to OPSCC in many studies. 17,52,[58][59][60][61][62][63] However, p16 is also strongly expressed in a subset of aggressive, lymph-node positive, cutaneous squamous carcinoma of the head and neck as well as benign branchial cysts. [64][65][66][67] Therefore, the use of p16 expression as a surrogate biomarker to OPSCC has limitations in SCCUP.…”

Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

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Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

2019

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Background Human papillomavirus (HPV)‐related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach. Aims This paper reviews the clinical presentation, diagnosis, and treatment of HPV‐related SCCUP. Materials and Methods The Medline/Pubmed database was searched by using the following keywords “CUP”, “cancer of unknown primary”, “HPV”, “human papilloma virus”, and “head and neck”. The references of the publications of interest were also screened for relevant papers. Results The clinical assessment of HPV‐related SCCUP includes a complete clinical examination, an endoscopic evaluation with white‐light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection. Discussion As a general approach, p16‐negative SCCUP are truly HPV negative, whereas p16‐positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive 18F‐FDG‐PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de‐escalation in HPV‐related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting. Conclusion Currently, the treatment of patients with HPV‐related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.

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Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

Section: Pathology and Hpv Assessmentmentioning

confidence: 99%

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

2019

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“…In addition, we excluded papers for not having HNCUP patient or for using patient data from public databases ( n = 9), for not describing diagnostic or prognostic biomarkers for HNCUP ( n = 4), and finally, for not showing statistically significant data ( n = 4). Finally, the review was performed on a total of 23 studies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. The flowchart of the systematic search is shown in Figure 3 .…”

Section: Resultsmentioning

confidence: 99%

“…Through p16 IHC, they confirmed the oropharyngeal primary origin for two of these patients (10%) [ 37 ]. In two case reports, the oropharyngeal primary origin was identified through p16 IHC [ 30 ]. In addition to detecting HPV in tissues, by using PCR for HPV DNA and IHC for p16, Schroeder et al investigated HPV in sera of 46 HNCUP.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Diagnostic and Prognostic Biomarkers for Head and Neck Cancer of Unknown Primary: An Unmet Clinical Need

et al. 2023

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Head and neck cancer of unknown primary (HNCUP) is defined as cervical lymph node metastases without a detectable primary tumor. The management of these patients presents a challenge to clinicians since guidelines in the diagnosis and treatment of HNCUP remain controversial. An accurate diagnostic workup is fundamental for the search for the hidden primary tumor to allow the best adequate treatment strategy. The purpose of this systematic review is to present the currently available data about the diagnostic and prognostic molecular biomarkers for HNCUP. Systematic research in an electronic database was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol and identified 704 articles, of which 23 studies were selected and included in the analysis. Fourteen studies investigated HNCUP diagnostic biomarkers and focused on the human papilloma virus (HPV) and the Epstein–Barr virus (EBV) due to the strong associations with oropharyngeal cancer and nasopharyngeal cancer, respectively. HPV status was shown to possess prognostic value, correlating with longer disease-free survival and overall survival. HPV and EBV are the only available HNCUP biomarkers, and they are already used in clinical practice. A better characterization of the molecular profiling and the development of tissue-of-origin classifiers are necessary to improve the diagnosis, staging, and therapeutic management of patients with HNCUP.

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p16 immunohistochemistry for primary tumor detection in HPV-positive squamous cell carcinoma of unknown primary

Shan¹,

Rooper²,

Ryan³

et al. 2021

American Journal of Otolaryngology

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p16 Immunohistochemistry Is a Useful Diagnostic Adjunct in Cases of Metastatic Cervical Carcinoma of Unknown Origin

Cited by 3 publications

References 9 publications

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

A Systematic Review of Diagnostic and Prognostic Biomarkers for Head and Neck Cancer of Unknown Primary: An Unmet Clinical Need

p16 immunohistochemistry for primary tumor detection in HPV-positive squamous cell carcinoma of unknown primary

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