Oncogenic viruses

Oncogenic viruses US Medical PG Question 1: A 38-year-old woman makes an appointment with her family physician for a routine check-up after being away due to travel for 1 year. She recently had a screening Pap smear, which was negative for malignancy. Her past medical history is significant for a Pap smear 2 years ago that reported a low-grade squamous intraepithelial lesion (LSIL). A subsequent colposcopy diagnosed high-grade cervical intraepithelial neoplasia (CIN2). The patient is surprised by the differences in her diagnostic tests. You explain to her the basis for the difference and reassure her. With this in mind, which of the following HPV serotypes is most likely to be present in the patient?

• A. HPV 33
• B. HPV 16 (Correct Answer)
• C. HPV 6
• D. HPV 31
• E. HPV 18

Oncogenic viruses Explanation: ***HPV 16*** - HPV 16 is the most common **high-risk HPV serotype**, responsible for approximately 50-60% of all **cervical cancers** and a high percentage of **high-grade cervical intraepithelial neoplasia (CIN2/3)**. The progression from LSIL to CIN2 in this patient suggests infection with a high-risk type, making HPV 16 the most likely candidate. - Given the patient's history of CIN2, a lesion of high-grade dysplasia, it is highly probable that she is infected with one of the most oncogenic HPV types, of which HPV 16 is paramount in prevalence. *HPV 33* - HPV 33 is a **high-risk HPV type** but is less prevalent than HPV 16 and 18 in causing cervical lesions. While it can cause CIN2, it is not the *most likely* serotype. - It accounts for a smaller proportion of cervical cancers and high-grade dysplasias compared to HPV 16. *HPV 6* - HPV 6 is a **low-risk HPV type** primarily associated with **genital warts (condyloma acuminata)** and **low-grade squamous intraepithelial lesions (LSIL)** that typically do not progress to CIN2 or cervical cancer. - Its presence would be inconsistent with the development of CIN2, as low-risk types are rarely implicated in high-grade dysplasia or malignancy. *HPV 31* - HPV 31 is another **high-risk HPV type** capable of causing **CIN2** and cervical cancer. However, it is less common than HPV 16. - While plausible, HPV 16 remains statistically the most probable cause of CIN2. *HPV 18* - HPV 18 is a **high-risk HPV type** and is the second most common cause of **cervical cancer**, particularly **adenocarcinoma**. It is also associated with high-grade squamous lesions. - While HPV 18 is a strong contender for high-grade lesions like CIN2, HPV 16 is still more frequently implicated in squamous cell carcinoma precursors.

Oncogenic viruses US Medical PG Question 2: A research group wants to assess the safety and toxicity profile of a new drug. A clinical trial is conducted with 20 volunteers to estimate the maximum tolerated dose and monitor the apparent toxicity of the drug. The study design is best described as which of the following phases of a clinical trial?

• A. Phase 0
• B. Phase III
• C. Phase V
• D. Phase II
• E. Phase I (Correct Answer)

Oncogenic viruses Explanation: ***Phase I*** - **Phase I clinical trials** involve a small group of healthy volunteers (typically 20-100) to primarily assess **drug safety**, determine a safe dosage range, and identify side effects. - The main goal is to establish the **maximum tolerated dose (MTD)** and evaluate the drug's pharmacokinetic and pharmacodynamic profiles. *Phase 0* - **Phase 0 trials** are exploratory studies conducted in a very small number of subjects (10-15) to gather preliminary data on a drug's **pharmacodynamics and pharmacokinetics** in humans. - They involve microdoses, not intended to have therapeutic effects, and thus cannot determine toxicity or MTD. *Phase III* - **Phase III trials** are large-scale studies involving hundreds to thousands of patients to confirm the drug's **efficacy**, monitor side effects, compare it to standard treatments, and collect information that will allow the drug to be used safely. - These trials are conducted after safety and initial efficacy have been established in earlier phases. *Phase V* - "Phase V" is not a standard, recognized phase in the traditional clinical trial classification (Phase 0, I, II, III, IV). - This term might be used in some non-standard research contexts or for post-marketing studies that go beyond Phase IV surveillance, but it is not a formal phase for initial drug development. *Phase II* - **Phase II trials** involve several hundred patients with the condition the drug is intended to treat, focusing on **drug efficacy** and further evaluating safety. - While safety is still monitored, the primary objective shifts to determining if the drug works for its intended purpose and at what dose.

Oncogenic viruses US Medical PG Question 3: A 41-year-old man with HIV comes to the physician because of rectal bleeding and itching for 2 weeks. During this period, he has also had pain with defecation. Four months ago, he was diagnosed with anogenital warts that were treated with cryotherapy. Over the past year, he has been sexually active with 3 male partners. He uses condoms inconsistently. Current medications are zidovudine, emtricitabine, and efavirenz. Digital rectal examination and anoscopy show an exophytic mass on the anal margin that is protruding into the anal canal. The mass is tender to palpation and bleeds easily on contact. Laboratory studies show a leukocyte count of 7,600/mm3 and a CD4+ T-lymphocyte count of 410/mm3 (N ≥ 500). A biopsy specimen of the lesion shows a well-differentiated squamous cell carcinoma. Which of the following cellular processes was most likely involved in the pathogenesis of this patient's malignancy?

• A. Activation of c-myc gene
• B. Inactivation of TP53 gene (Correct Answer)
• C. Activation of TAX gene
• D. Inactivation of VHL gene
• E. Inactivation of WT1 gene

Oncogenic viruses Explanation: ***Inactivation of TP53 gene*** - This patient's **squamous cell carcinoma** (SCC) of the anus is strongly associated with **human papillomavirus (HPV) infection**, which is common in HIV-positive sexually active men. HPV oncoproteins, particularly E6, promote the degradation of the **TP53 tumor suppressor protein**. - Inactivating mutations or degradation of **TP53** remove a critical checkpoint in the cell cycle, allowing cells with DNA damage to proliferate uncontrollably and contributing to carcinogenesis. *Activation of c-myc gene* - The **c-myc proto-oncogene** is involved in cell proliferation, differentiation, and apoptosis, and its activation is commonly seen in lymphomas (e.g., Burkitt lymphoma) and other cancers. - While *c-myc* activation can contribute to various malignancies, it is not the **primary molecular mechanism** linked to HPV-associated anal squamous cell carcinoma. *Activation of TAX gene* - The **TAX gene** is a transforming gene of **human T-cell lymphotropic virus type 1 (HTLV-1)**, responsible for T-cell leukemia/lymphoma. - This patient's presentation with anal squamous cell carcinoma, rather than a hematologic malignancy, makes HTLV-1 and TAX gene activation an unlikely cause. *Inactivation of VHL gene* - The **VHL (Von Hippel-Lindau) gene** is a tumor suppressor gene whose inactivation is strongly associated with **renal cell carcinoma** (clear cell type) and other tumors like pheochromocytoma and hemangioblastoma. - Inactivation of **VHL** is not a primary mechanism in the development of anal squamous cell carcinoma. *Inactivation of WT1 gene* - The **WT1 (Wilms tumor 1) gene** is a tumor suppressor gene primarily associated with **Wilms tumor**, a kidney cancer that typically affects children. - Inactivation of **WT1** is not a known pathogenic mechanism for anal squamous cell carcinoma in adults.

Oncogenic viruses US Medical PG Question 4: A 63-year-old man presents to his primary care physician because he has been having headaches and hearing loss. In addition, he says that he has been having difficulty opening his jaw to eat and recurrent middle ear infections. Physical exam reveals enlarged neck lymph nodes and a mass in the nasopharynx. Biopsy of the mass reveals undifferentiated squamous epithelial cells. The organism that is most likely associated with this patient's disease is also associated with which of the following disorders?

• A. Kaposi sarcoma
• B. Hepatocellular carcinoma
• C. Adult T-cell lymphoma
• D. Burkitt lymphoma (Correct Answer)
• E. Vulvar carcinoma

Oncogenic viruses Explanation: ***Burkitt lymphoma*** - The patient's symptoms (headaches, hearing loss, difficulty opening jaw, recurrent middle ear infections, nasopharyngeal mass, enlarged neck lymph nodes) and biopsy results (undifferentiated squamous epithelial cells) point to **nasopharyngeal carcinoma**. - **Nasopharyngeal carcinoma** is strongly associated with the **Epstein-Barr virus (EBV)**. EBV is also a causative agent in **Burkitt lymphoma**. *Kaposi sarcoma* - **Kaposi sarcoma** is caused by **Human Herpesvirus 8 (HHV-8)**, not EBV. - It typically presents as vascular skin lesions and can affect visceral organs, differing from the nasopharyngeal carcinoma described. *Hepatocellular carcinoma* - **Hepatocellular carcinoma** is primarily associated with **Hepatitis B virus (HBV)** and **Hepatitis C virus (HCV)** infection, as well as cirrhosis from other causes. - There is no significant association between EBV and hepatocellular carcinoma. *Adult T-cell lymphoma* - **Adult T-cell lymphoma** is caused by the **Human T-lymphotropic virus type 1 (HTLV-1)**. - This is a retrovirus distinct from EBV. *Vulvar carcinoma* - **Vulvar carcinoma** is most frequently associated with **Human Papillomavirus (HPV)** infection, especially high-risk strains like HPV 16 and 18. - It is not typically linked to EBV.

Oncogenic viruses US Medical PG Question 5: Two viruses, X and Y, infect the same cell and begin to reproduce within the cell. As a result of the co-infection, some viruses are produced where the genome of Y is surrounded by the nucleocapsid of X and vice versa with the genome of X and nucleocapsid of Y. When the virus containing genome X surrounded by the nucleocapsid of Y infects another cell, what is the most likely outcome?

• A. Virions containing genome Y and nucleocapsid Y will be produced
• B. No virions will be produced
• C. Virions containing genome X and nucleocapsid Y will be produced
• D. Virions containing genome Y and nucleocapsid X will be produced
• E. Virions containing genome X and nucleocapsid X will be produced (Correct Answer)

Oncogenic viruses Explanation: ***Virions containing genome X and nucleocapsid X will be produced*** - The virus containing **genome X** surrounded by **nucleocapsid Y** is a pseudotype. During the infection of a new cell, the **genome X** will direct the synthesis of new viral components, including **nucleocapsid X**. - Since the genetic material (genome X) dictates the production of viral proteins, the new virions will be genetically identical to virus X, thus containing its own genome and nucleocapsid. *Virions containing genome Y and nucleocapsid Y will be produced* - This is incorrect because the infecting particle carried **genome X**, not genome Y. - The genetic information encoded in the genome determines the type of progeny viruses produced. *No virions will be produced* - This is unlikely as the pseudotyped virus is capable of infection and delivery of a functional genome into the host cell. - The cell is presumed to be permissive for virus replication. *Virions containing genome X and nucleocapsid Y will be produced* - This would only happen if the **nucleocapsid Y** was somehow replicated independently of its original genome, which is not how viral replication works. - The progeny nucleocapsids are always encoded by the genome that is replicating within the cell. *Virions containing genome Y and nucleocapsid X will be produced* - This is incorrect. The infecting virus introduced **genome X** into the cell, not genome Y. - The genetic material delivered determines the type of viral particles that will be synthesized.

Oncogenic viruses Flashcard 1 of 5

Question: What is the cancer risk associated with HPV31?_____

Answer: High

Oncogenic viruses Flashcard 2 of 5

Question: Where is EBV latent?_____

Answer: B cells

Oncogenic viruses Flashcard 3 of 5

Question: Which Herpesvirus is associated with Nasopharyngeal Carcinoma?_____

Answer: EBV

Oncogenic viruses Flashcard 4 of 5

Question: What is the cancer risk associated with HPV6? _____

Answer: Low

Extra Information:    https://onlinemeded.org/spa/microbiology/dna-viruses/acquire?ref=anki 

Oncogenic viruses Flashcard 5 of 5

Question: What do the vaccines for HPV 6, 11, 16, 18, target? _____ of the virus

Answer: Capsid proteins

Extra Information:   Watch Human papillomavirus (Papillomaviridae) [https://dashboard.sketchy.com/study/medical/courses/medical-microbiology/units/medical-microbiology-viruses/videos/medical-microbiology-viruses-dna-viruses-human-papillomavirus-papillomaviridae?utm_source=anki&utm_medium=partnership&utm_campaign=february_update&utm_content=medical] https://onlinemeded.org/spa/pediatrics/vaccinations/acquire?ref=anki