Snapshot of Clinical Implications of p16 Overexpression in Carcinogenesis

Molecular markers are needed to decide the treatment plans of certain cancer types when the histological and other clinical diagnoses are not sufficient to decide the tumor nodular metastasis (TNM) stage. The ubiquitous p16 gene is one of them gained popularity by fulfilling criteria to be a useful biomarker. Over expression of p16, to compensate the inactivity of another two tumor suppressor genes (TSG)s, pRb and p53 due to the integration of E7 and E6 high risk Human Papilloma viral oncoprotein respectively into the host keratinocytes is useful to consider the clinical impact of p16 biomarker in carcinogenesis. The p16 immunohistochemistry helps the diagnosis as well as prognosis of cervical and oropharyngeal squamous cell carcinoma, though there are ambiguities in the cutoff values of p16 positivity. There is also a re-emerging interest on clinical impact of p16 positivity in lung, breast, and colorectal cancer types. High risk HPV genotypes have been already established as the aetiological agents of cervical, other rare ano-genital and oropharyngeal (especially tonsils and base of the tongue) cancers. The HPV associated subset of head and neck cancers demonstrate a unique tumor biology, when compared with HPV non associated ones thus, most effective treatment planning including counselling is much needed to maximize the overall survival of HPV associated cancer patients, in the era of personalized precision medicine. In the shed of light, this communication glimpses on clinical implications of p16 overexpression in carcinogenesis not limiting to cervical and a subset of head and neck carcinomas (HNSCC).

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Performance of a 31-gene expression profile (GEP) test for metastatic risk prediction in cutaneous melanomas (CM) of the head and neck.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.9576 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 9576-9576

Author(s):

John T. Vetto ◽

Sancy Ann Leachman ◽

Brooke Middlebrook ◽

Kyle R. Covington ◽

Jeffrey D. Wayne ◽

...

Keyword(s):

High Risk ◽

Head And Neck ◽

Distant Metastasis ◽

False Negative ◽

Tumor Biology ◽

False Negative Rate ◽

Neck Region ◽

Negative Rate ◽

Class 1 ◽

Metastatic Risk

9576 Background: Accurate prognostication of distant metastatic risk using sentinel lymph node (SLN) biopsy for CM can be challenging in melanomas of the head and neck due to a higher false negative rate compared to other anatomical areas. A GEP signature that predicts metastatic risk based on primary tumor biology, providing a binary outcome of Class 1 (low risk of metastasis) or Class 2 (high risk), was previously described. The prognostic capabilities of the GEP independently and in combination with SLN status in a cohort of patients with primary head and neck CM are assessed here. Methods: All samples and clinical data were collected under an IRB-approved multicenter protocol. qPCR analysis was used to assess expression of the gene signature (Class 1 vs. Class 2). Distant metastasis-free survival (DMFS) and melanoma-specific survival (MSS) were assessed. Results: 157 subjects with primary CMs in the head and neck region were identified. 110 of 157 subjects had a SLN biopsy performed. Median age was 65 years (range 25-89) and median Breslow depth was 1.6 mm (range 0.2-15.0 mm). In 71 SLN-negative patients, 18 of 27 (67%) distant metastatic events were GEP Class 2. Overall, 73% (47 of 64) distant metastases, and 88% (22 of 25) deaths due to CM were called Class 2. By comparison, sensitivities for DMFS and MSS were 41% (26 of 64) and 52% (13 of 25), respectively, using SLN biopsy alone, and increased to 80% (51 of 64) and 88% (22 of 25), respectively, when combining the SLN status and GEP class. Kaplan-Meier 5-year DMFS and MSS rates based on SLN status alone or in combination with GEP are shown in the table. Conclusions: These data support the ability of the GEP test to accurately identify low- and high-risk cases of head and neck melanoma. The results strongly support the role of GEP testing to enhance current staging by better predicting the risk of distant metastasis and death for patients with melanoma in an anatomic region that is associated with a higher SLN biopsy false negative rate. [Table: see text]

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Clinical Implications of Human Papillomavirus in Head and Neck Cancers

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.1291 ◽

2006 ◽

Vol 24 (17) ◽

pp. 2606-2611 ◽

Cited By ~ 317

Author(s):

Carole Fakhry ◽

Maura L. Gillison

Keyword(s):

Human Papillomavirus ◽

High Risk ◽

Head And Neck ◽

Sexual Behaviors ◽

Hpv Infection ◽

Genetic Alterations ◽

Sufficient Evidence ◽

Clinical Implications ◽

Risk Of Death ◽

Increased Risk

Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.

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Dietary intervention modulates the expression of the splicing machinery in patients at high-risk of type 2 diabetes development: clinical implications

Endocrine Abstracts ◽

10.1530/endoabs.56.oc4.1 ◽

2018 ◽

Author(s):

Rio-Moreno Mercedes del ◽

Emilia Alors-Perez ◽

Antonio Camargo ◽

Javier Delgado-Lista ◽

Juan L. Lopez-Canovas ◽

...

Keyword(s):

Type 2 Diabetes ◽

High Risk ◽

Dietary Intervention ◽

Clinical Implications ◽

Diabetes Development ◽

Splicing Machinery

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Faculty Opinions recommendation of Prospective study of sentinel node biopsy for high-risk cutaneous squamous cell carcinoma of the head and neck.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725486356.793508151 ◽

2015 ◽

Author(s):

Ian Maher ◽

Stephanie R Jackson Cullison

Keyword(s):

Squamous Cell Carcinoma ◽

High Risk ◽

Prospective Study ◽

Sentinel Node ◽

Cell Carcinoma ◽

Head And Neck ◽

Sentinel Node Biopsy ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Node Biopsy

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Weekly cisplatin (40 mg/m2) versus three-weekly (100mg/m2) cisplatin delivered concurrently with radiotherapy in high risk head and neck cancer patients

ALEXMED ePosters ◽

10.21608/alexpo.2020.41597.1023 ◽

2020 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Mahinour Bassiouny

Keyword(s):

Head And Neck Cancer ◽

High Risk ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Weekly Cisplatin

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Clinical impact of LncRNA XIST and LncRNA NEAT1 for diagnosis of high-risk group breast cancer patients

Current Problems in Cancer ◽

10.1016/j.currproblcancer.2021.100709 ◽

2021 ◽

pp. 100709

Author(s):

Menha Swellam ◽

Hekmat M EL Magdoub ◽

May A Shawki ◽

Marwa Adel ◽

Mona M Hefny ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Risk Group ◽

High Risk Group ◽

Clinical Impact ◽

Breast Cancer Patients ◽

Lncrna Xist ◽

Lncrna Neat1

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The effects of a preoperative multidisciplinary conference on outcomes for high-risk patients with challenging surgical treatment options: a retrospective study

BMC Anesthesiology ◽

10.1186/s12871-021-01257-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Masayoshi Koike ◽

Mie Yoshimura ◽

Yasushi Mio ◽

Shoichi Uezono

Keyword(s):

Patient Safety ◽

Retrospective Study ◽

High Risk ◽

Treatment Plan ◽

Treatment Options ◽

High Risk Patients ◽

Appropriate Treatment ◽

Risk Patients ◽

Treatment Plans ◽

Multidisciplinary Conference

Abstract Background Surgical options for patients vary with age and comorbidities, advances in medical technology and patients’ wishes. This complexity can make it difficult for surgeons to determine appropriate treatment plans independently. At our institution, final decisions regarding treatment for patients are made at multidisciplinary meetings, termed High-Risk Conferences, led by the Patient Safety Committee. Methods In this retrospective study, we assessed the reasons for convening High-Risk Conferences, the final decisions made and treatment outcomes using conference records and patient medical records for conferences conducted at our institution from April 2010 to March 2018. Results A total of 410 High-Risk Conferences were conducted for 406 patients during the study period. The department with the most conferences was cardiovascular surgery (24%), and the reasons for convening conferences included the presence of severe comorbidities (51%), highly difficult surgeries (41%) and nonmedical/personal issues (8%). Treatment changes were made for 49 patients (12%), including surgical modifications for 20 patients and surgery cancellation for 29. The most common surgical modification was procedure reduction (16 patients); 4 deaths were reported. Follow-up was available for 21 patients for whom surgery was cancelled, with 11 deaths reported. Conclusions Given that some change to the treatment plan was made for 12% of the patients discussed at the High-Risk Conferences, we conclude that participants of these conferences did not always agree with the original surgical plan and that the multidisciplinary decision-making process of the conferences served to allow for modifications. Many of the modifications involved reductions in procedures to reflect a more conservative approach, which might have decreased perioperative mortality and the incidence of complications as well as unnecessary surgeries. High-risk patients have complex issues, and it is difficult to verify statistically whether outcomes are associated with changes in course of treatment. Nevertheless, these conferences might be useful from a patient safety perspective and minimize the potential for legal disputes.

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Systemic Therapy for Head and Neck Skin Cancers

FACE ◽

10.1177/27325016211013880 ◽

2021 ◽

pp. 273250162110138

Author(s):

Rebecca Knackstedt ◽

Peter Taub ◽

Gary Rogers ◽

Brian Gastman

Keyword(s):

Radiation Therapy ◽

High Risk ◽

Head And Neck ◽

Systemic Therapy ◽

Malignant Tumors ◽

Curative Therapy ◽

Recurrent Tumors ◽

Skin Cancers ◽

Systemic Therapies ◽

Melanoma Skin

The mainstay of curative therapy for head and neck skin cancers relies upon surgery and/or radiation therapy. However, for some aggressive, non-resectable or recurrent tumors, systemic therapy is necessary. Recent emerging classes of drugs have shown to improve survival for high-risk, recurrent, and unresectable variants of these tumors. The goal of this paper is to review options for systemic therapies for head and neck skin cancers including melanoma, non-melanoma skin cancers and other rare and non-malignant tumors.

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