HPV E6 oncoproteins and nucleic acids in neck lymph node fine needle aspirates and oral samples from patients with oropharyngeal squamous cell carcinoma

Chernesky, Max; Jang, Dan; Schweizer, Johannes; Amaris, Manuel A.; Doerwald-Munoz, Lilian; Gupta, Michael; Jackson, B. Stanley; Archibald, Stuart; Young, James K.; Lytwyn, Alice; Śmieja, Marek; Severini, Alberto; Ecobichon-Morris, Anne; Hyrcza, Martin

doi:10.1016/j.pvr.2018.05.003

Cited by 25 publications

(27 citation statements)

References 37 publications

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“…To the best of our knowledge, this is the first study to investigate the presence of both these biomarkers in a large group of cancer‐free individuals with a commercially available assay for HPV mRNA detection that has been fully validated for cervical cancer screening . So far, the Aptima HPV assay has been used only to detect HPV mRNA in the saliva of patients with OPC . Another study reported HPV mRNA detection in oral rinses but used homemade, nonstandardized methods and included only patients with HNC …”

Section: Discussionmentioning

confidence: 99%

“…22 So far, the Aptima HPV assay has been used only to detect HPV mRNA in the saliva of patients with OPC. 19 Another study reported HPV mRNA detection in oral rinses but used homemade, nonstandardized methods and included only patients with HNC. 17 In the current study, we first investigated the presence of HPV DNA, and we found that approximately 10% of the subjects were positive for high-risk types, with no significant differences between HIV-infected and uninfected subjects.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, HPV mRNA detection in oral specimens is very challenging because mRNA is highly susceptible to degradation by the enzymes present in oral fluids. Oral rinses, saliva, and swabs have been used only marginally for HPV mRNA detection in patients with OPC . To the best of our knowledge, no studies have reported HPV mRNA detection in oral rinses of cancer‐free individuals.…”

Section: Introductionmentioning

confidence: 99%

“…Oral rinses, saliva, and swabs have been used only marginally for HPV mRNA detection in patients with OPC. [17][18][19] To the best of our knowledge, no studies have reported HPV mRNA detection in oral rinses of cancer-free individuals.…”

Section: Introductionmentioning

confidence: 99%

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Oral testing for high‐risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection

Rollo¹,

Pichi²,

Benevolo³

et al. 2019

Cancer

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Background Testing for oral high‐risk human papillomavirus (HPV) DNA may be useful for identifying individuals at increased risk for HPV‐driven oropharyngeal cancer (OPC). However, positivity for HPV DNA provides no information on the transforming potential of the infection. In contrast, the detection of high‐risk HPV E6/E7 messenger RNA (mRNA) may help to identify clinically significant infections because of the indispensable role of E6/E7 viral oncoproteins in the carcinogenic process. Methods Oral rinses were collected with a mouthwash from cancer‐free individuals at increased risk for oral HPV infection. High‐risk HPV DNA and mRNA were evaluated via the testing of the oral rinses with the Linear Array HPV genotyping test and the Aptima HPV assay, respectively. Results Overall, 310 subjects with no clinical evidence of lesions of the oral cavity and oropharynx were included in the study. Thirty‐three (10.6%) harbored high‐risk HPV DNA in their oral rinse. These cases, together with 10 random samples negative for high‐risk HPV DNA, were tested with the Aptima assay. A valid result was obtained for 41 of the 43 specimens (95.3%). Among the 31 cases that were positive for high‐risk HPV DNA and had a valid Aptima result, 4 (12.9%) were positive for HPV mRNA. HPV mRNA was not detected in any of the samples negative for high‐risk HPV DNA. Conclusions HPV mRNA is detectable in oral rinses of cancer‐free subjects. Oral HPV mRNA testing may be useful in the screening and/or early detection of HPV‐driven OPC by possibly identifying active and transforming oral infections. The testing of individuals at increased risk for HPV‐related OPC via simply and noninvasively collected oral specimens is an attractive option for future screening strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oral testing for high‐risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection

Rollo¹,

Pichi²,

Benevolo³

et al. 2019

Cancer

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“…Another option for testing cytology aspirates for high‐risk HPV is molecular testing of aspirate material collected into a liquid‐based fixative in a fashion similar to that for cervicovaginal cytology. A variety of molecular assays, including Hybrid Capture 2, Cobas 4800, and Aptima, have been examined in the literature, with most studies showing correlations for HPV similar to what has been reported for p16 IHC . This strategy of using molecular HPV assays on liquid‐based cytology samples of neck aspirate material can confirm the presence of high‐risk HPV even for cystic metastases, for which cell block sections more frequently lack sufficient material for p16 IHC.…”

mentioning

confidence: 93%

p16 immunocytochemistry on aspirate smears of neck masses: Another option for determining the HPV status in metastatic head and neck squamous cell carcinoma

Griffith

2019

Cancer Cytopathology

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A recent study has demonstrated the potential for performing p16 immunocytochemistry on routinely collected aspirate smears of metastatic squamous cell carcinoma of the head and neck. In some cases, p16 immunocytochemistry on already collected aspirate smears may be the only available option, so this could be a valuable method that eliminates the need for repeat sampling before clinical staging and management decisions.

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CDKN2A/p16 evaluation in cytology specimens

Xing¹,

Griffith²

2023

Cancer Cytopathology

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Cyclin-dependent kinase inhibitor 2A (CDKN2A) is an important tumor suppressor gene located at 9p21.3 that expresses p16 and p19through alternate reading frames. Mutations or losses of CDKN2A are central to tumorigenesis in a wide variety of tumors because p16 plays an important role in cell cycle regulation through inhibition of CDK4 and CDK6. p16 activity on CDK4/6 reduces phosphorylation of pRB and thus reduces transcriptional activity of E2F and arrests cell cycle progression from the G 1 phase to the S phase (Figure 1A). p19 interacts with MDM2, and this results in p53 stabilization and promotes cell cycle arrest and apoptosis. An evaluation of CDKN2A/ p16 status and/or expression can be useful in cytology specimens in a few specific circumstances, as detailed in this brief article. p16 function is commonly lost in a wide variety of cancersApproximately 50% of all human cancers show some form of p16 inactivation. Reduced p16 function is tumorigenic because of increased cell cycling from reduced negative regulation on the G 1 -S checkpoint (Figure 1B). A reduction or loss of p16 function occurs through a variety of mechanisms, including point mutations, loss of heterozygosity, homozygous deletion (HD), and promoter methylation. The precise mechanisms and their proportions are dependent on the tumor type. [1][2][3][4][5] Interestingly, a loss of p16 function correlates with more aggressive disease in some tumor types. [6][7][8][9][10] Despite the frequency of altered p16 function in cancer, molecular evaluation of p16 alterations is not frequently used clinically in cytology samples. One exception to this is the increasing use of p16 evaluation for effusion cytology specimens for mesothelioma. In addition, immunohistochemical detection of p16 overexpression is an important diagnostic tool in the diagnosis of high-risk human papillomavirus (HR-HPV)-associated oropharyngeal squamous cell carcinomas (OPSqCCs) from cytology specimens. p16 testing for malignant mesotheliomaMalignant pleural mesothelioma (MPM) is an aggressive malignancy, and patients often present with pleural effusions. Although pleural biopsy is the gold standard for diagnosis, this procedure is invasive and may not be tolerated. Additionally, effusion cytology specimens are usually received in pathology laboratories earlier in a patient's course, and this potentially allows an earlier diagnosis. Making an accurate and prompt diagnosis of MPM with cytology specimens is paramount. An increasing number of biomarkers are now available to distinguish reactive mesothelial proliferations from mesothelioma.Previously, the International Mesothelioma Interest Group stated that cytology was insufficient for a diagnosis of MPM; however, more recent guidelines include cytology as an acceptable method but require the incorporation of ancillary studies for confirmation. 11 In the following discussion, it is also important to note that the high specificity of these studies is dependent on confirmation of the mesothelial nature of tumor cells (i.e., not adenocar...

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HPV E6 oncoproteins and nucleic acids in neck lymph node fine needle aspirates and oral samples from patients with oropharyngeal squamous cell carcinoma

Cited by 25 publications

References 37 publications

Oral testing for high‐risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection

Oral testing for high‐risk human papillomavirus DNA and E6/E7 messenger RNA in healthy individuals at risk for oral infection

p16 immunocytochemistry on aspirate smears of neck masses: Another option for determining the HPV status in metastatic head and neck squamous cell carcinoma

CDKN2A/p16 evaluation in cytology specimens

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