A 48-year-old woman comes to the office due to a sore throat for the past 3 months. On examination, she is found to have an enlarged, ulcerated left tonsil and a firm, nontender, nonmobile left neck mass. The patient undergoes biopsy of the tonsil. Pathology is consistent with squamous cell carcinoma. Further analysis of the biopsy specimen shows expression of viral genome proteins. Which of the following most likely predisposed the patient to the development of this malignancy?

Question

A 48-year-old woman comes to the office due to a sore throat for the past 3 months.  On examination, she is found to have an enlarged, ulcerated left tonsil and a firm, nontender, nonmobile left neck mass.  The patient undergoes biopsy of the tonsil.  Pathology is consistent with squamous cell carcinoma.  Further analysis of the biopsy specimen shows expression of viral genome proteins.  Which of the following most likely predisposed the patient to the development of this malignancy?

Quizplus · Accepted Answer

11ec160b_39fa_02a5_9249_31c0314b89c7_MD0001_00 Tumor formation is driven by the accumulation of mutations that lead to uncontrolled cell growth. Two types of genes can be altered to increase malignant potential: Oncoviruses can induce cancer-forming mutations through the expression of proteins that activate protooncogenes or inactivate tumor suppressor genes. Human papillomavirus (HPV) is implicated in several types of cancer, including head and neck, cervical, anal, and penile cancer. HPV produces viral oncoproteins E6 and E7, both of which affect tumor suppressors: (Choices A and C) BRAF encodes for a serine/threonine-specific protein kinase involved in regulating the mitogen-activated protein kinase signaling pathway. It is often mutated in melanoma, non-Hodgkin lymphoma, and papillary thyroid cancer. RET encodes for a receptor tyrosine kinase and is associated with multiple endocrine neoplasia (MEN) 2A, MEN 2B, and papillary thyroid cancer. Both RET and BRAF are protooncogenes that require gain-of-function mutations to become oncogenes. Decreased activity can protect against uncontrolled proliferation (eg, BRAF inhibitors used in melanoma). (Choices D and E) BRCA1 and BRCA2 (associated with breast, ovarian, and pancreatic cancers) encode a DNA repair protein. MEN1 (associated with MEN1) encodes for the protein menin, which has diverse functions that may be related to regulation of cell cycle kinase inhibitor and homeobox genes. Both BRCA1/2 and MEN1 are tumor suppressor genes, meaning that their inactivation (rather than overexpression) leads to tumor development. Educational objective: Inactivation of retinoblastoma protein activity by human papillomavirus can lead to the formation of head and neck squamous cell carcinoma. __________ References: The role of HPV E6 and E7 oncoproteins in HPV-associated cervical carcinogenesis. (http://www.ncbi.nlm.nih.gov/pubmed/19956366) The molecular landscape of head and neck cancer. (http://www.ncbi.nlm.nih.gov/pubmed/29497144)

A 48-Year-Old Woman Comes to the Office Due to a Sore