Question

A 36-year-old female has a routine physical. She is single, doesn’t smoke and has a few drinks of alcohol a week. She began menarche at age 11 and her first sexual intercourse was at age 14. She has had numerous sexual partners and does not regularly use barrier contraception. Physical examination is normal. The Pap smear comes back as atypical squamous cells of undetermined significance (ASCUS).

a. What risk factors does she have for cervical cancer?

b. Describe the pathogenesis of Human Papilloma Virus.

c. Why should HPV testing be done and what are the tests to be ordered?

d. What HPV subtypes are associated with cervical cancer?

e. Explain the role of E6 and E7 HPV proteins in cervical cancer.

f. Differentiate between Human Papilloma Virus and Herpes Simplex virus

Answer 1

Ans) a) Risk factors for cervical cancer:

- Human papillomavirus (HPV) infection
- Immune system deficiency.
- Herpes.
- Smoking.
- Age.
- Socioeconomic factors.
- Oral contraceptives.
- Exposure to diethylstilbestrol (DES).

b) Pathogenesis of Human papillomavirus:

- HPV infection occurs at the basal cell layer of stratified squamous epithelial cells. Infection stimulates cellular proliferation in the epithelium and infected cells display a broad spectrum of changes, ranging from benign hyperplasia to dysplasia to invasive carcinoma.

c) Need for HPV testing:

Woman aged 30-36- The American Cancer Society recommends women in this age group have an HPV test with a pap smear (co-testing) every five years.
- If you are a woman of any age that gets an abnormal result on a pap smear.
- HPV testing in not recommended for women younger than 30 who have had normal pap smear results. Cervical cancer is rare in this age group, but HPV infections are common. Most HPV infections in young women clear up without treatment.

- An HPV test is usually done at the same time as a Pap test — a test that collects cells from your cervix to check for abnormalities or the presence of cancer. An HPV test can be done using the same sample from the Pap test or by collecting a second sample from the cervical canal.

d) The most common subtypes among these cases were HPV16, HPV18, HPV58, HPV53, and HPV33. High-risk HPVs are known to be the primary cause of cervical cancer.

e) The HPV E6 and the E7 proteins modulate cellular proteins that regulate the cell cycle (reviewed in references 35 and 38).

- E6 protein binds to the p53 tumor suppressor protein and targets it for accelerated ubiquitin-mediated degradation. The E6 protein also stimulates telomerase activity in cultured keratinocytes.

f) Differences between Human papillomavirus and Herpes Simplex virus –

- While both cause skin issues, the manifestations are different.

- Herpes causes sores around or in the mouth and on the genitals. Unlike herpes, HPV often has no symptoms, but usually is the cause of genital warts. HPV can cause cancer, making it arguably the most dangerous of the two STDs.