USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 50-year-old man presents to the office with a two-month history of hoarseness and sore throat. He initially came to the office approximately two months ago with similar symptoms and was treated empirically for an upper respiratory infection. Since then, he has developed night sweats and experienced a 2 kg (4.4 lb) weight loss. He has not experienced heartburn, hearing loss, epistaxis, or nasal congestion. He smokes one pack of cigarettes per day and consumes 3 alcoholic beverages daily. Vital signs are within normal limits. On physical examination, the left tonsil is enlarged, with an area of ulceration present on the mucosa. Overproduction of which of the following proteins is most likely involved in the pathogenesis of this patient’s condition?
Content Reviewers:Rishi Desai, MD, MPH
Human papillomaviruses, or HPV for short, are a group of non-enveloped DNA viruses that specifically infect human epithelial cells.
There are over 100 different types of HPVs which can be categorized by the epithelial cells they prefer to infect; like cutaneous epithelial cells of the skin, especially the face, hands and feet; and epithelial cells of mucous membranes, especially the respiratory tract including the pharynx, and nasal and oral cavities; and anal and genital regions.
Some types can cause benign tumors, called papillomas or warts; and some can lead to carcinomas, or cancer of the epithelial cells.
HPV may have contributed to both actor Michael Douglas’s throat cancer diagnosis, and former first lady of Argentina, Eva Perón’s fatal cervical cancer.
Epithelial cells line the outer surfaces of organs and blood vessels and separate the interior of the body from the external world.
They primarily serve as a protective barrier to invasion by pathogenic bacteria, fungi, parasites and viruses; and to water loss.
In locations like the skin, anus, genitals, and respiratory tract, they can be stratified, having more than one layer of epithelial cells.
At the base, the layer closest to the interior of the body, these cells are less mature, rounded stem cells, also called basal cells.
Basal cells divide and replenish all the cells found in the epithelium.
As the basal cells divide and mature, they move toward the outermost layer, flattening out and becoming more squamous shaped in appearance.
Once they reach the top layer, these mature, flat cells are exfoliated, or shed, from the epithelium.
Now, typically basal cells are well protected under all those layers.
But if there are abrasions or cuts in the epithelium, HPV can gain access to and infect the basal cells.
Once that happens, HPV can replicate with or without being incorporated into the basal cell’s DNA through the activities of two particular viral genes called E6 and E7.
The proteins of these genes cause dysregulation of tightly-scheduled replication of the epithelial cells by altering the p53 and retinoblastoma protein (pRB) tumor suppressor pathways that typically prevent unregulated growth of the epithelial cells.
In this way, HPV causes uncontrolled replication of the epithelial cells, forming warts, and disrupts the normal structure of the epithelium, forming lesions.
In some types of HPV infections, a squamous epithelial cell can become a koilocyte, or a cells with an irregular shape, enlarged and dark staining nucleus, and a clear area around the nucleus that’s called a perinuclear halo.
These cells are typical of precancerous lesions that can transform into carcinomas when the abnormal epithelial cells break through the basement membrane of the epithelium and invade other tissues.
The cause of an HPV infection is contact with infected epithelial cells.
And infections are more likely if a person is already immunocompromised.
Now, many HPV infections are asymptomatic, but when symptoms are present, they can vary by HPV type.
So, symptoms of nongenital cutaneous infections can involve some kind of benign wart.