Human Papillomavirus Infections — MCQs
LMP 1 gene plays a role in oncogenesis induced by
At what age is the first dose of Measles vaccination given under the Universal Immunization Programme (UIP)?
Genital warts are caused by:
A patient with HIV presents with extensive anogenital warts. Which HPV types are most commonly associated with malignant transformation in this setting?
Which of the following is NOT typically associated with chronic HPV infection?
A female patient presents with multiple sessile lesions on the vulva that do not bleed on touch. What is the most likely diagnosis?
An 18-year-old woman presents for follow-up of an abnormal Pap smear that revealed an abnormality suggestive of HPV infection. Which of the following was the likely cytopathologic finding?
What is the target gene that is affected by the E6 gene product of HPV, leading to malignant transformation?
A 32-year-old gay male presented to his community STD clinic with perianal condyloma acuminatum. Physical removal was recommended due to the size of the lesions, along with topical immunomodulatory therapy. Which of the following drugs was most likely selected?
Which one of the following statements best characterizes lympho-granuloma venereum (LGV)?
Human Papillomavirus Infections Indian Medical PG Practice Questions and MCQs
Question 1: LMP 1 gene plays a role in oncogenesis induced by
- A. Hepatitis B virus
- B. Human T cell leukemia virus type 1
- C. Human papilloma virus
- D. Epstein Barr virus (Correct Answer)
Explanation: ***Epstein Barr virus*** - The **LMP1 (Latent Membrane Protein 1)** gene is a key **oncogene** encoded by the **Epstein-Barr virus (EBV)**. - LMP1 acts as a **constitutively active receptor**, mimicking CD40 and leading to the activation of several cellular signaling pathways (**NF-κB, JNK/p38, PI3K/Akt**) crucial for cell proliferation, survival, and differentiation. *Hepatitis B virus* - **Hepatitis B virus (HBV)** is associated with **hepatocellular carcinoma (HCC)**, but its oncogenic mechanisms primarily involve the **HBx protein**, which deregulates cell cycles and impacts host gene expression. - HBV does not encode an LMP1 equivalent; its oncogenesis is linked to chronic inflammation, hepatocyte regeneration, and integration of viral DNA. *Human T cell leukemia virus type 1* - **Human T-cell leukemia virus type 1 (HTLV-1)** is linked to **Adult T-cell Leukemia/Lymphoma (ATL)**, with its primary oncogene being **Tax**. - **Tax protein** activates NF-κB and other pro-proliferative pathways, but HTLV-1 does not have an LMP1 gene. *Human papilloma virus* - **Human papillomavirus (HPV)** is responsible for cervical and other anogenital cancers, with major oncogenes being **E6 and E7**. - **E6 targets p53** for degradation, and **E7 inactivates Rb**, leading to uncontrolled cell division; HPV does not encode an LMP1 gene.
Question 2: At what age is the first dose of Measles vaccination given under the Universal Immunization Programme (UIP)?
- A. 10 weeks
- B. 9 months (Correct Answer)
- C. 14 weeks
- D. 6 months
Explanation: ***9 months*** - The first dose of the **Measles-Rubella (MR) vaccine** is given at **9 months of age** as per India's Universal Immunization Programme (UIP). - This timing is chosen because **maternal antibodies** against measles, which can interfere with vaccine effectiveness, generally wane by this age. - A second dose is given at **16-24 months** to ensure adequate protection (Note: Some countries use MMR vaccine which includes mumps component as well). *10 weeks* - This age is associated with the administration of other routine vaccinations like **Pentavalent vaccine (DPT-HepB-Hib)** and **OPV/IPV**, not measles. - Administering the measles vaccine too early, when **maternal antibodies** are still high, leads to suboptimal immune response. *14 weeks* - This is when the **third dose of Pentavalent vaccine and OPV/IPV** are given as part of the routine immunization schedule. - This age is not the standard recommendation for initial measles vaccination. *6 months* - While specific high-risk situations (e.g., outbreaks or travel to endemic areas) might warrant an additional measles vaccine dose at 6 months, it is **not the routine recommended age** for the first dose. - At 6 months, there may still be sufficient **maternal antibodies** to interfere with vaccine efficacy, leading to poorer immune response compared to vaccination at 9 months. - If given at 6 months during outbreaks, the child still receives routine doses at 9 months and 16-24 months.
Question 3: Genital warts are caused by:
- A. Human Papilloma Virus (Correct Answer)
- B. Chlamydia trachomatis
- C. Epstein Barr virus
- D. HSV
Explanation: ***Human Papilloma Virus*** - **Human Papilloma Virus (HPV)** is the primary cause of genital warts, particularly low-risk types like **HPV-6** and **HPV-11**. - HPV infection is common and is transmitted primarily through **sexual contact**. *Chlamydia trachomatis* - **Chlamydia trachomatis** is a bacterium that causes a common sexually transmitted infection (STI), leading to **urethritis**, **cervicitis**, and pelvic inflammatory disease, but not genital warts. - It can cause symptoms like **dysuria** and **vaginal discharge**, or be asymptomatic, but does not result in wart-like lesions. *Epstein Barr virus* - **Epstein-Barr virus (EBV)** is a herpesvirus primarily known for causing **infectious mononucleosis** (glandular fever). - It is associated with certain cancers like nasopharyngeal carcinoma and lymphomas but not with sexually transmitted genital warts. *HSV* - **Herpes Simplex Virus (HSV)** causes **genital herpes**, characterized by painful **blisters** and **sores** that typically recur. - While HSV is a sexually transmitted infection, the lesions it causes are vesicular and ulcerative, distinctly different from the fleshy, wart-like lesions of HPV.
Question 4: A patient with HIV presents with extensive anogenital warts. Which HPV types are most commonly associated with malignant transformation in this setting?
- A. Types 42 and 43
- B. Types 31 and 33
- C. Types 16 and 18 (Correct Answer)
- D. Types 6 and 11
Explanation: ***Types 16 and 18*** - **HPV types 16 and 18** are considered **high-risk** and are responsible for the majority of HPV-related cancers, including cervical, anal, and oropharyngeal cancers. - In HIV-positive individuals, the risk of malignant transformation from HPV infection is significantly increased due to **immunocompromise**. *Types 42 and 43* - **HPV types 42 and 43** are classified as **low-risk** HPV types. - They are primarily associated with **benign anogenital warts** and rarely cause malignant transformation. *Types 31 and 33* - **HPV types 31 and 33** are also considered **high-risk** types and can cause malignant transformation. - However, **types 16 and 18** are more frequently associated with HPV-related cancers than types 31 and 33. *Types 6 and 11* - **HPV types 6 and 11** are **low-risk** types and are the primary cause of **genital warts (condyloma acuminata)**. - While they can cause extensive warts, they have a very low potential for malignant transformation.
Question 5: Which of the following is NOT typically associated with chronic HPV infection?
- A. Integration into host genome
- B. Increased p53 activity (Correct Answer)
- C. Expression of E6 and E7 proteins
- D. Cellular proliferation
Explanation: ***Increased p53 activity*** - Chronic **HPV infection**, particularly by high-risk types, leads to the expression of the viral **E6 protein**, which targets **p53 for degradation**. [3] - Therefore, chronic HPV infection is typically associated with **decreased p53 activity**, not increased, as E6's role is to neutralize this tumor suppressor. [2] *Integration into host genome* - This is a hallmark of transforming infections by high-risk **HPVs**, allowing for stable expression of **viral oncogenes** like E6 and E7. - This integration is crucial for the development of HPV-associated malignancies, as it ensures persistent expression of viral proteins that disrupt **cell cycle control**. [1] *Expression of E6 and E7 proteins* - **E6 and E7** are the main viral oncogenes expressed during persistent **high-risk HPV infection**. - **E6 targets p53** for degradation, and **E7 inactivates retinoblastoma protein (pRb)**, leading to uncontrolled cell proliferation. [2] *Cellular proliferation* - The effects of **E6 and E7** on **p53 and pRb** remove the checks and balances on cell growth, promoting **uncontrolled cellular proliferation**. [1] - This excessive proliferation is a key step in the development of **HPV-associated neoplasia and cancer**. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 334-335. [3] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Lung, pp. 739-741.
Question 6: A female patient presents with multiple sessile lesions on the vulva that do not bleed on touch. What is the most likely diagnosis?
- A. Molluscum
- B. Condyloma acuminata (Correct Answer)
- C. Herpes genitalis
- D. Chancroid
Explanation: ***Condyloma acuminata*** - **Condyloma acuminata**, also known as genital warts, are typically **sessile or pedunculated lesions** with a verrucous (cauliflower-like) appearance, commonly found on the vulva. - These lesions are caused by the **human papillomavirus (HPV)** and generally do not bleed on touch unless traumatized. *Molluscum* - **Molluscum contagiosum** presents as **dome-shaped, pearly papules** with a central umbilication, not sessile lesions. - The lesions are typically smaller and have a characteristic central dimple. *Herpes genitalis* - **Herpes genitalis** presents as painful **vesicles or ulcers** that often rupture and form crusts, not sessile lesions. - These lesions are typically accompanied by pain and itching. *Chancroid* - **Chancroid** is characterized by one or more **painful, soft chancres** with irregular, undermined borders and a grayish base that often bleeds easily. - Ulcers are the hallmark of chancroid, not sessile growths.
Question 7: An 18-year-old woman presents for follow-up of an abnormal Pap smear that revealed an abnormality suggestive of HPV infection. Which of the following was the likely cytopathologic finding?
- A. Fibroids
- B. Koilocytes (Correct Answer)
- C. Donovan bodies
- D. Clear cells
Explanation: ***Koilocytes*** - **Koilocytes** are **pathognomonic cellular changes** indicative of **HPV infection** on a Pap smear [1], [2] - These cells are characterized by an **enlarged nucleus**, often **hyperchromatic**, with a **perinuclear halo** (a clear zone around the nucleus) and cytoplasmic changes [1], [2] - This is the classic cytopathologic finding that confirms HPV infection in cervical cytology [2] *Fibroids* - **Uterine fibroids** are **benign smooth muscle tumors** of the uterus and are not detected by a Pap smear, which screens for cervical cellular abnormalities - They typically present with heavy menstrual bleeding, pelvic pressure, or pain, and are diagnosed via imaging like ultrasound - Fibroids are structural lesions, not cytopathologic findings *Donovan bodies* - **Donovan bodies** are intracellular inclusions found in macrophages and are diagnostic of **granuloma inguinale** (also known as donovanosis) - This is a bacterial sexually transmitted infection caused by *Klebsiella granulomatis* - Associated with genital ulcers and are not related to HPV infection or Pap smear findings *Clear cells* - **Clear cells** are a type of cell seen in specific **adenocarcinomas**, such as **clear cell carcinoma of the vagina or cervix**, which are rare - While these are malignant cells, their presence is not suggestive of HPV infection but rather a specific type of cancer - Clear cell carcinoma has historically been associated with in utero DES (diethylstilbestrol) exposure **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, p. 1010. [2] Cross SS. Underwood's Pathology: A Clinical Approach. 6th ed. Common Clinical Problems From Female Genital Tract Disease, pp. 466-467.
Question 8: What is the target gene that is affected by the E6 gene product of HPV, leading to malignant transformation?
- A. C-myc gene (proto-oncogene)
- B. N-myc gene (proto-oncogene)
- C. p53 gene (tumor suppressor gene) (Correct Answer)
- D. RAS gene (involved in signaling)
Explanation: ***p53 gene (tumor suppressor gene)*** - The **E6 gene product of HPV** inactivates the **p53 tumor suppressor protein**, which normally functions to halt cell growth or induce apoptosis in response to DNA damage [1], [2]. - Degradation of p53 by E6 leads to **uncontrolled cell proliferation** and genomic instability, contributing significantly to malignant transformation [1]. *C-myc gene (proto-oncogene)* - While **c-myc** is a proto-oncogene involved in cell growth and proliferation, it is not the primary target directly affected by the HPV E6 protein. - Activation of c-myc can be a secondary event in carcinogenesis, but it's not the direct mechanism by which E6 promotes malignancy. *N-myc gene (proto-oncogene)* - **N-myc** is another proto-oncogene, often associated with neuroblastoma, and is not a direct target of the HPV E6 oncoprotein. - Its role in HPV-induced cancers is not central to the mechanism of E6. *RAS gene (involved in signaling)* - The **RAS gene** is a proto-oncogene encoding proteins involved in cell signaling pathways that regulate cell growth and differentiation [2]. - Mutations in RAS are common in various cancers, but the HPV E6 protein does not primarily target or inactivate the RAS gene or its protein products for malignant transformation. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. The Female Genital Tract, pp. 1007-1008. [2] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Neoplasia, pp. 301-304.
Question 9: A 32-year-old gay male presented to his community STD clinic with perianal condyloma acuminatum. Physical removal was recommended due to the size of the lesions, along with topical immunomodulatory therapy. Which of the following drugs was most likely selected?
- A. Acyclovir (antiviral)
- B. 5-Fluorouracil (chemotherapy)
- C. Imiquimod (topical immunomodulator) (Correct Answer)
- D. Podophyllin (antimitotic agent)
Explanation: ***Imiquimod (topical immunomodulator)*** - **Imiquimod** is a topical immunomodulator that stimulates the production of **cytokines**, such as **interferon-alpha**, thereby enhancing the local immune response against **HPV-infected cells**. - It is a common and effective therapy for external **genital** and **perianal warts (condyloma acuminatum)**, often used in conjunction with other treatments, especially for larger lesions. *Acyclovir (antiviral)* - **Acyclovir** is an antiviral drug primarily used to treat infections caused by the **herpes simplex virus (HSV)** and **varicella-zoster virus (VZV)**, not **human papillomavirus (HPV)**. - While condyloma acuminatum is caused by **HPV**, acyclovir has no therapeutic effect against it. *5-Fluorouracil (chemotherapy)* - **5-Fluorouracil** is a **cytotoxic chemotherapy agent** that inhibits **DNA synthesis** and is sometimes used topically for certain skin cancers and actinic keratoses. - While it can be used for warts, it is generally considered an off-label use and is **less commonly chosen** for perianal condyloma acuminatum due to significant local irritation and potential for ulceration. *Podophyllin (antimitotic agent)* - **Podophyllin** is a **cytotoxic agent** that arrests cell division and is used topically to treat some types of warts by causing **necrosis** of the wart tissue. - While effective, its application has to be carefully performed by a clinician, and it is **contraindicated in pregnancy**; it is also not classified as an immunomodulator.
Question 10: Which one of the following statements best characterizes lympho-granuloma venereum (LGV)?
- A. It is most common in temperate regions
- B. The causative agent is C. trachomatis (Correct Answer)
- C. In the United States, it is more common among women
- D. Penicillin is effective in early treatment
Explanation: **The causative agent is *C. trachomatis*** - **Lymphogranuloma venereum (LGV)** is a sexually transmitted infection caused by specific serovars (**L1, L2, L2a, L2b, L3**) of *Chlamydia trachomatis*. [1] - These serovars are **invasive** and replicate in **mononuclear phagocytes** of lymphatic tissue, leading to the characteristic lymphadenopathy. [1] *It is most common in temperate regions* - LGV is **most common in tropical and subtropical regions**, particularly in parts of Africa, Southeast Asia, South America, and the Caribbean. - Its prevalence is much lower in temperate regions, though outbreaks can occur, especially in specific *high-risk populations*. *In the United States, it is more common among women* - In developed countries like the United States, LGV primarily affects **men who have sex with men (MSM)**, particularly those who are HIV-positive. [1] - While it can occur in women, its incidence is **significantly lower** in this population. *Penicillin is effective in early treatment* - LGV is caused by *Chlamydia trachomatis*, which is a **bacterium that lacks a peptidoglycan cell wall**, making it inherently resistant to penicillin. - The recommended treatments for LGV are **doxycycline** or **erythromycin**, not penicillin.
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