A 45-year-old man comes to the office due to a sore throat for the past 3 months. The patient also has pain with swallowing. He has never smoked, drinks alcohol occasionally, and does not use illicit drugs. On physical examination, the right tonsil is enlarged with a small area of ulceration. The rest of the physical examination is unremarkable. Biopsy of the right tonsil is shown in the image below: Which of the following most likely played the most significant role in the pathogenesis of this patient's condition?

Question

A 45-year-old man comes to the office due to a sore throat for the past 3 months.  The patient also has pain with swallowing.  He has never smoked, drinks alcohol occasionally, and does not use illicit drugs.  On physical examination, the right tonsil is enlarged with a small area of ulceration.  The rest of the physical examination is unremarkable.  Biopsy of the right tonsil is shown in the image below:  Which of the following most likely played the most significant role in the pathogenesis of this patient's condition?

Quizplus · Accepted Answer

11ec160b_382b_f95e_9249_6d64093e2e27_MD0001_00 Biopsy of the ulcerative tonsil lesion in this patient with persistent throat pain shows malignant cells with atypical mitotic figures and keratin pearls, findings consistent with head and neck mucosal squamous cell carcinoma (HNSCC). Although most head and neck cancers are linked to tobacco and excessive alcohol use, patients with oropharyngeal carcinoma (eg, tonsil, base of tongue) often lack traditional risk factors. Instead, oropharyngeal cancer is frequently associated with human papillomavirus (HPV) exposure, particularly in younger patients. HPV-positive HNSCC primarily affects the oropharynx, possibly due to the higher concentration of lymphatic tissue facilitating viral processing. The most common causative subtypes are HPV-16 and 18, which are covered by the HPV vaccine. HPV is a nonenveloped, double-stranded DNA virus that infects cutaneous and mucosal tissues. Some strains (eg, HPV-1, HPV-2) cause skin warts. Others (eg, HPV-6, HPV-11) cause anogenital papillomas or papillomas that affect the upper respiratory tract (ie, recurrent respiratory papillomatosis). High-risk strains (eg, HPV-16, HPV-18) produce proteins (E6, E7) that prevent apoptosis, promote cellular proliferation, and cause genetic instability; they are also linked to cancer of the cervix, vulva, anus, and penis. (Choice A) Coxsackievirus is the leading cause of hand-foot-and-mouth disease, which is characterized by low-grade fever, oral macules/vesicles, and a macular/papular/vesicular rash on the hands, feet, and extremities. This virus does not typically cause malignant transformation. (Choice B) Epstein-Barr virus (EBV) can also cause HNSCC; however, it is most specifically implicated in the nasopharynx, rather than the oropharynx. The classic triad of nasopharyngeal carcinoma is a neck mass, nasal obstruction, and a unilateral, persistent middle ear effusion due to obstruction of the eustachian tube. (Choice C) Herpes simplex virus causes latent infection in the sensory nerves. It is associated with vesicular lesions of the orolabial mucosa, not tonsillar ulcers, and does not cause HNSCC. (Choice D) HIV increases the risk of many types of cancer due to immune dysregulation. The risk of cancers related to underlying infections, such as human herpesvirus 8 (Kaposi sarcoma), HPV, EBV, and hepatitis B and C viruses (hepatocellular carcinoma), is particularly increased. However, oropharyngeal cancer is most tightly linked to underlying HPV infection even in the setting of HIV. Educational objective: Most oropharyngeal carcinomas (eg, tonsil, base of tongue) are caused by human papilloma virus (HPV) infection. HPV-16 and HPV-18 are particularly likely to cause malignant transformation. __________ References: HPV associated head and neck cancer. (http://www.ncbi.nlm.nih.gov/pubmed/27527216)

A 45-Year-Old Man Comes to the Office Due to a Sore