HPV

Question 1

What genital HPV is and how to prevent it

Answer 1

• Small double stranded DNA viruses that infect basal cells of mucosa (do not circulate in blood), very high prevalence
• Best way to prevent it is avoiding sexual activities and/or getting vaccinated
• Best way to detect is PAP smear and HPV DNA tests

Question 2

How genital HPV is transmitted and how it escapes the immune system 1

Answer 2

• Transmitted via mucosa-mucosa contact (not blood)
• Rarely see vertical transmission
• Oral sex, anal and vaginal sex transmission is common
• Virus can only replicate in basal cells (access them via micro wound in epidermis)
• Virus can infect langerhans cells, which causes them to move to lymphatics w/o activating the dendritic cells in the dermis thus avoiding an immune response to the virus

Question 3

How genital HPV is transmitted and how it escapes the immune system 2

Answer 3

• Decreased T cell numbers leads to increased risk of HPV, and most HPV infections are cleared in a yr by T cells (since it takes 1 yr HPV must be evading T cells)
• HPV T cell immune evasion mechanisms: low profile, molecular mimicry, skewing of cytokine profiles, modulation of Ag presentation, interference w/ interferon response, modulation of cell adherence molecules, modulation of langerhans cells

Question 4

To which diseases it is linked and how you can prevent or treat them 1

Answer 4

• Types 6 and 11 associated w/ venereal warts
• Types 16, 18 associated w/ cervical, vaginal, vulvar, penile, anal, and oro-pharyngeal CA
• Virus alone produces 2 hits, but need 3 hits to get CA (smoking may be 3rd hit)
• > 95% of women infected w/ HPV will be clear of the virus 1 yr after infection
• Most HPV infections are either ASx or produce CIN1 (in females), the vast majority of which resolve
• A smaller number of HPV infections produce CIN2 (some may resolve, some may progress) and an even smaller number produce CIN3 (usually progresses)
• CIN2/3 (AKA HSIL) have a higher probability of progressing into CA

Question 5

To which diseases it is linked and how you can prevent or treat them 2

Answer 5

• Prevention: abstinence, fewer sex partners, screening, vaccines
• Vaccines (gardasil) will only protect against strains of HPV that have not yet been contracted- will do nothing for the active infections
• Current Rx options: low-grade lesions just observation, high-grade lesions do loop electrical excision procedure (LEEP)
• May be possible to generate a vaccine w/ CD8 T cells that target cervical CA cells and thus destroy the CA (therapeutic vaccine)
• Ipilimumab is Ab against CTLA-4 (which causes CD8 T cells to shut down), injections of it can lead to increased T cell response to cervical CA

Question 6

What issues remain in elimination of cervical CA by vaccination

Answer 6

• Vaccine is a virus-like particle w/ L1 protein (causes immune response), it is not infectious or pathogenic
• HPV vaccines will not work against active infections, will not improve abnormal PAP smears or cervical CA
• Multiple HPV types are linked to cervical CA and vaccines do not yet cover all of these types
• Unknown how long protection lasts (at least 10 yrs)
• Other issues: target population is 9-12, must reach poor people who need it most, false security- pap smears must be continued, timeframe to observe the effects on cervical CA long (25 yrs), social/political/fear barriers