HPV, warts, cervical cancer Flashcards
HPV structure
non-enveloped dsDNA virus. Capsid proteins L1 and L2
List the early vs late genes for HPV
early: replication (E1), trxn (E2) and transformation genes (E5-7). Late: major (L1) and minor capsid proteins (L2)
Which HPV genes are oncogenes
E5, E6 and E7. All code for cell proliferation and transformation genes.
What is the long control region of HPV
Promoter region- DNA replication origin and controls viral gene expression
HPV life cycle
HPV Life Cycle is Linked to Stratified Epithelial Cell Differentiation. It only infects undifferentiated proliferating basal layer cells and it is released by the fully differentiated upper layer cells
HPV transmission
Sex, genital-genital, manual-genital, oral-genital (condoms don’t fully protect). Mother to newborn (vertical transmission, rare) or fomites (surgical gloves, clothes, etc, not well documented)
risk factors for HPV
early intercourse (before age 20), multiple partners, hx of genital warts, immunosuppressive disorders, failure to receive pap smears, long term use of contraceptives, smoking
Define a persistent HPV infection
Detection of same HPV type two or more times over 1 year. Persistence of high risk HPV is crucial for cancer development. Factors associated with persistent infection: >30 yrs, infection with multiple HPV types, immune suppression
Normal HPV course
In women 15-25 years of age, ~80% of HPV infections are transient and cleared within 1 year (Median duration of infection = 8 months)
- Identify high and low risk HPVs
Mucosal HPV- high risk: 16, 18, 31,33, 35, 39, 45, 51, 52, 56, 58, 59. low risk: 6, 11, 40, 42, 43, 44. Cutaneous HPV: 1, 2, 5, 7, 8, 14, 17, 20, 47
describe common wart and HPV types associated with it
Verruca vulgaris- small, rough tumor typically on hands and feet but often other locations. HPV 2 and 7
Describe plantar wart and HPV types associated with it
verruca plantaris- occurs on sole or toes of foot. HPV 1, 2, 4
Describe anogenital warts and HPV types associated with them
condyloma acuminatum- sexually transmitted disease, highly contagious. HPV 6, 11 and others
describe respiratory papillomatosis and HPV types associated with it
warts form on larynx or other areas of respiratory tract. HPV 6 and 11
Epidermodysplasia verruciformis
rare autosomal recessive disease
characterized by abnormal susceptibility to HPV
(various genotypes). Growths occur on the skinrare autosomal recessive disease
characterized by abnormal susceptibility to HPV
(various genotypes). Growths occur on the skin
Which HPVs are associated with cervical cancer
HPV16 (50%), HPV 18 (20%), HPV 31, HPV 33, HPV 45 (25%)
Where do HPV cervical cancers arise
~99% of HPV-associated cervical cancers arise within the transformation zone (area of immature metaplasia between original and current squamocolumnar junction)
List the cancers associated with HPV
cervical (100%), head and neck (25%), vaginal (50%), vulvar (50%), penile (50%), anal (50%), non-melanoma skin cancers (90%), non-small cell lung cancers (20% asia)
describe cervical cancer progression (WHO histopath)
normal > cervical intraepithelial neoplasia 1 (CIN1) > CIN2/3 > cancer
describe cervical cancer progression (Bethesda classification)
normal > atypical squamous cell of undetermined significance (ASCUS) > low-grade squamous intraepithelial lesion > high grade squamous intraepithelial lesion > cancer
What percentage of those infected with HPV will develop cancer, clear the infection or progress to CIN2/3
80% will be infected and clear the infection. 10% will progress to CIN2/3 after 7-15 years
HPV oncogenes functions
E6 and E7 are highly expressed in cancers. They inhibit p53 (E6) and Rb (E7). Cancer regresses when they are blocked
functions of p53 and Rb
p53 causes cell cycle arrest and apoptosis in response to cellular stress and DNA damage. Rb binds to E2F and causes cell cycle arrest by stopping trxn of genes for cell cycle progression.
What causes uncontrollable expression of HPV E6/E7
- Disruption of E2 functions as a E6/E7 inhibitor
- Increase of viral gene transcription by host cell
promoters and enhancers. 3. More stable 3’ UTR from host chromosome
