HPV and cervical cancer

Question 1

1. Define unique features of HPV structure and life cycle.

Answer 1

1. non-enveloped icosahedral DNA viruses that are most commonly associated with skin warts.
   L1 protein on outside

E6 protein binds and degrades p53, thus inhibiting cell senescence.

The E7 protein binds pRB, releasing the E2F transcription factor, and thereby activates genes involved in DNA replication and cell cycle progression.

Life cycle- “epitheliotropic”

virus entry to basal cells of the epithelium, usually after skin damage. Papillomavirus transcription, replication, and assembly are intimately linked to the differentiating layers of the epithelium as the basal cell divides and progresses through its developmental program. Only at the epithelial surface are the capsid protein genes transcribed, translated, and virus released.

Question 2

2. Identify high and low risk HPVs and their associated diseases.

Answer 2

Anogenital wart (condyloma acuminatum): one of the most common sexually transmitted disease, highly contagious e.g. HPV6 & HPV11

6) Squamous cell carcinomas: cervical cancer, head and neck cancer: e.g. HPV16, HPV18, HPV31, HPV33, HPV45

Question 3

3. Describe the HPV oncoproteins and their important cellular targets.

Answer 3

The E6 and E7 proteins of these HPVs were then found to bind p53 and pRB, respectively, giving a mechanistic rationale for their oncogenic potential. Moreover, during
the time course to neoplastic transformation, the circular HPVgenome was found to integrate into the host cell chromosome, and thereby usually disrupted the E2 gene. E2 represses E6 and E7 transcription, and thus its disruption allows for greater E6 and E7 expression levels.
“high-risk”.

Question 4

4. Explain how HPV-associated lesions could be diagnosed.

Answer 4

1. Pap Smear Test
   The Papanicolaou smear test is a screening test used in gynecology to determine premalignant and malignant processes in the ectocervix, detecting cytologic evidence of HPV infection and tissue abnormality.
   -cytology

2. HPV Testing
 PCR technique has been a common method to detect HPV DNA in specimen but recently other tests using various approaches have been developed for more accurate and comprehensive diagnosis of HPV infections.
• DNA Detection
- Digene Hybrid Capture II (HC2)
- Roche cobas HPV Test
- Abbott RealTime High Risk HPV test
• mRNA Detection
- Norchip PreTect HPV Proofer - Hologic Aptima HPV
• Protein Detection
- BD ProEx C
- Ventana CINtec® p16

3. Colposcopy
   If your Pap smear is abnormal the next step is colposcopy, using binocular instrument, called colposcope, to look closer at cervix. Many times, it is combined with biopsies for further pathological examination.

Question 5

5. Explain how the current HPV vaccines are made and what their limitations are.

Answer 5

11-26 years old

all made to the L1 protein of different strains
VLPs of L1 protein made in yeast with aluminum adjuvant

Gardasil-6,11,16,18
Cervarix- 6 18 VLPs of L1 protein made in insect cells with AS04 adjuvant

Gardasil 9- 6,11,16,18, 32…VLPs of L1 protein made in yeast with aluminum adjuvant

Question 6

risk factors for HPV

Answer 6

early onset intercourse
multiple sex parteners
history of genital warts
immunosuppresive disorders

Question 7

Tx

Answer 7

Surgery