This group of viruses can cause the findings seen in the clinical image below.

Which of the following statements is/are true about how certain strains can contribute to carcinogenesis? (hint: more than one answer may be correct)

A. E6 binds to p53 

B. E7 binds to p53

C. E6 binds to RB

D. E7 binds to RB

E. EVER1 mutation

Rationale: The clinical photograph above shows a classic presentation of verruca on the foot caused by Human papillomavirus (HPV). HPV is a double-stranded DNA virus that infects human keratinocytes and can lead to the development of warts and certain cancers such as cervical cancer and squamous cell carcinoma. 

Correct answers: A and D

E6 and E7 are oncoproteins most commonly seen in high-risk subtypes of HPV (16, 18, 31, 33, 45). E6 binds to p53, a known tumor suppressor, leading to ubiquitin degradation of p53 and thus decreased apoptosis. E7 binds to RB and RB normally inhibits E2F (transcription factor); the binding of E7 to RB leads to increased cellular proliferation. Targeting these mechanisms in certain tumors may be beneficial. 

Incorrect answers: 

B and C: These answer choices are the opposite mechanisms of how E6 and E7 work as oncoproteins.

E. EVER1 (and EVER2) mutations are seen in epidermodysplasia verruciformis. This is an autosomal recessive disorder in which patients are more susceptible to beta-genus HPV. Clinically these patients present with fairly generalized warts that may look like tinea versicolor with hypopigmented or hyperpigmented patches and some patients present with seborrheic keratoses-like lesions. Patients with epidermodysplasia verruciformis are at risk of lesions having malignant transformation, particularly in sun exposed areas. 

Additional reading at Chapter 25: Human Papillomavirus-Associated Skin Cancers

Pal A, Kundu R. Human Papillomavirus E6 and E7: The Cervical Cancer Hallmarks and Targets for Therapy. Front Microbiol. 2020 Jan 21;10:3116. doi: 10.3389/fmicb.2019.03116.