Exam 3- Lecture 6: HPV Vaccines

What is Human Papillomavirus (HPV)?

• Most adults (>80%) get HPV in lifetime

  • 90% of infections resolve in 2 years

  • Most common STI in US

    • 80 million Americans currently infected

• Over 150 types/strains of HPV

  • Some cause common & genital warts (HPV 6 & 11)

  • Some cause cancer (cervical, mouth/throat, anus/rectum, penile)

• Vaccine was introduced in 2006

What is cervical cancer?

2nd leading type of cancer in women

• HPV 16 & 18 cause at least 70% of cervical cancers

• 99.7% of cervical cancers have HPV DNA

• By 50 years of age, at least 80% of women will have acquired a genital HPV infection

What is the most common age at infection for HPV?

• 15-24 years old

• HPV 16 & 18 persist the longest

  • Targets “transformation zone”

What is HPV prevention?

• Condoms are helpful, but not 100% effective

• Vaccines are available!

  • Gardasil-4 was introduced in 2006

    • Initially recommended for women (11-26)

  • Gardasil 9 was approved in Dec 2014

    • As of 2017, only Gardasil-9 was available in US

• Also recommended for men

  • Protection against genital warts

  • Protection against penile & oral/throat cancers

  • Reduce risk of spread

What is HPV treatment?

• Identification & monitoring are critical

• Pap smears

What is HPV detection via Pap smears?

• Large, darker staining nuclei w/ irregular shapes

• Normal cells w/ small, regular nuclei (normal)

What is HPV?

• Naked DNA virus

  • Outermost layer is composed of capsid protein called L1

    • L stands for “late” as in its a late/structural gene

  • L1 spontaneously self-assembles

    • Does not require any other viral proteins to assemble

• Neutralizing antibody is generated against L1

What are the vaccines for HPV?

• In US, only Gardasil 9 is available today

  • Covers 9 strains

    • HPV 6 & 11: cause of genital warts

    • HPV 16, 18, 31, 33, 45, 52, & 58: oncogenic strains

What does Gardasil not include?

Live virus

• Adjuvant= aluminum hydroxyphosphate sulfate

  • Most aluminum exposure is through diet & antacids

  • Low doses of aluminum salts can act as adjuvants

  • Stimulates a specific antibody response

• Antigen= viral-like particles

  • Composed of only 1 viral protein (L1)

  • No genetic material (no DNA)

What are virus-like particles (VLPs)?

Not infectious (no DNA or other proteins) & are not oncogenic

What does it mean that VLPs are highly immunogenic?

• Produces high levels of antibodies & B-cell memory

  • Antibody levels are 1-4 logs higher than natural infection

  • Antibody levels maintained for 7-10 yrs post-vaccination

    • Protection against cancer seen 10 years out

  • Some antibodies are cross protective against other HPV strains that are not in vaccines

• Produces sterilizing immunity in most subjects

  • Complete protection w/o any detectable virus

• Even low levels of neutralizing antibodies are protective against disease

What do VLPs produce?

Consistent antibody responses across population

• Percentage of women who seroconvert after Gardasil vaccination (99%)

• Antibody response occurs w/in weeks of immunization

  • Quicker than natural infection

Why does vaccine produce a better antibody response than natural infection?

• May be due to route of immunization

  • IM route→ VLPs reach lympathics & lymph nodes

    • Greater antigen presentation & CMI in lymph nodes

• Natural infection

  • Virus is mostly mucosal

  • Antibody response takes much longer to form (months)

What do HPV vaccines protect against?

Infection and cancer

• Vaccinated women (14-24) have >90% reduction in HPV 16/18 infections

  • Unvaccinated women had decrease of 74%

  • Suggests herd immunity is having an effect

• Cervical cancer rates are decreasing in young women (20-24)

  • Declined by total of 33% from 2005-2012

  • Declined 65% from 2012-2019

• Rates of other cancers (anal, penile, head/neck) are also declining

Who can receive the HPV vaccine?

• Routine vaccination recommended at age 11-12

  • Prior to sexual activity

  • Different dosing based on age

    • Vaccine initiated at 9-14: 2 doses

    • Vaccine initiated at >15: 3 doses

Who can receive the HPV vaccine? (Cont)

• Gardasil 9 also approved for ages 27-45 (men & women)

• Based upon a 3.5 year study of Gardasil in women 27-45

  • 88% effective in preventing genital warts, precancerous lesions, & cervical cancer

• Use is dependent on shared clinical decision making

Who cant receive the HPV vaccine?

• Life-threatening rxn to a prior dose of vaccine

• Life-threatening rxn to yeast

  • Used to generate VLPs

What are the limitations of HPV vaccines?

• Prophylactic vaccines

  • Effective at preventing HPV prior to exposure

• Not therapeutic vaccines

  • If someone already has HPV, will not reduce disease duration/infection

  • May protect against other strands

• Issues w/ finishing schedule

  • 2021:

    • 59% of teens were up to date of HPV vaccine

    • 77% of 13-17yo had received first dose

  • Push to reduce # of doses

    • May be possible w/ future engineering

What do recent studies suggest w/ fewer doses?

Still protect against cancer

• For Gardasil 4:

  • 1, 2, or 3 doses is associated w/ lower incidence of pre invasive cervical disease

    • Compared to unvaccinated group

  • For high grade cervical disease, 3-dose group was best protected

Does HPV vaccine change behavior of recipients?

• Concerns HPV vaccines would lead to sexual disinhibition

• Multiple studies demonstrated vaccine is not associated w/ increased sexual activity

Why may parents hesitate to vaccinate their kids?

• Safety concerns & perceived “lack of necessity” are main reasons for refusing HPV vaccine

• Vaccination rate in teen girls increased from 37.2% to 69.9% from 2008-18

Do HPV vaccines have unusual side effects?

NO

• Clinical trials & post-market surveillance demonstrate that is safe & well tolerated

• Most common issues:

  • Mild injection site rxns

  • Syncope (fainting)- seen w/ other vaccinations given to adolescents

• More severe AEs were not substantiated upon further study

  • Venous thromboembolism, demyelinating diseases