HPV VACCINES Dr. Kirtan Krishna

Introduction 10% of yearly cancers worldwide (>1 million cases per year) are caused by viral infections HPV contributes to 6,00,000 cases per year Human papillomaviruses are a group of more than 200 related viruses. Spread -direct sexual contact -skin and mucous membranes Schiller JT, Lowy DR: Virus infection and human cancer: An overview, in Chang MH, Jeang K-T (eds): Viruses and Human Cancer. Heidelberg, Germany, Springer, 2014, pp 1-10

TWO CATEGORIES: LOW-RISK HPV’S : skin warts (condylomata acuminata) on or around the genitals, anus, mouth, or throat.ex: HPV types 6 and 11 HIGH-RISK HPV’S: cancer. Ex:HPV types 16,18,31,33,35,39,45,51,52,56,58,59,66. They are responsible for 70% of cervical cancers.

Most HPV infections are asymptomatic 90% are cleared within 2 yrs Only 50-60% develop serum antibodies to HPV after natural infection 40% of those with HPV infection had no cervical cytological abnormality

Cancers caused by HPV Approximately 99.7% of cervical cancers 60% of oropharyngeal cancers 91% of anal cancers 75% of vaginal cancers 69% of vulvar cancers 63% of penile cancers HPV 16 is the most predominant oncogenic genotype Centers for Disease Control and Prevention: Prevention of genital HPV infection and sequelae: Report of an external consultants’ meeting. http://www.cdc.gov/std/hpv/hpvsupplement99.pdf

HPV vaccines Available since 2006 Protein subunit vaccine Prepared from virus like particles by recombinant technology. They do not contain any live biological product or DNA so they are non infectious Gardasil & cervarix approved in 100 countries Both vaccines offer protection of atleast 5 yrs with ongoing studies of their full duration of their effect In December 2014, the US FDA approved Gardasil-9, which adds protection against five oncogenic HPV types (ie, 31, 33, 45, 52, and 58) . It prevents approximately 90% of cervical, vulvar, vaginal, and anal cancers

BIVALENT (CERVARIX) QUADRAVALENT (GARDASIL) 9-VALENT (GARDASIL- 9) Manufacturer Glaxosmith kline Merck L1 VLP types 16,18 6,11,16,18 6,11,16,18,31,33,4552,58 Manufacturing Trichoplusia ni insect cell line infected with L1 encoding recombinant baculovirus Saccharomyces cerevisiae( Baker’s yeast) –expressing L1 Licensed Females 9-45 years Females 9-26 years Males 9-25 years Males 9-15 years Dosing 0,1,6 0,2,6

CDC Recommendation All boys and girls age 11 or 12 years should get vaccinated - early vaccination as greater immunorectivity For adults, men -age 21 years women - age 26 years Gay and bisexual men - age 26 years Men and women with compromised immune systems - age 26 years if they did not get fully vaccinated at a younger age

All girls age 9 to 13 yrs - two-dose vaccine schedule with an interval of 6 months Women >15 yrs or immunocompromised - three-dose schedule 0,2 and 6months

Site of administration Deltoid region of the upper arm

Severe allergies , including a severe allergy to yeast should be brought to the notice. Mild illness can get the vaccine. If they are moderately or severely ill- delay until they recover.

Vaccination in pregnancy Not recommended for pregnant women.   If unknowingly vaccinated during pregnancy they can continue pregnancy , no effect on mother and baby. Women who are breastfeeding may be vaccinated.

Side effects Mild injection site pain (approximately 9 out of 10) swelling (approximately 1 in 3) Fever (approximately 1 in 8) headache, and fatigue (approximately 1 in 2)

EFFICACY Highly effective if given before initial exposure to the virus. 1 month after the third dose 100% have detectable antibody to each HPV genotype, level is 10 – 104 times higher than natural infection Gardsasil & cervarix – 90% against 16,18 GARDASIL 9: 90% of cervical cancers and 78% of anal cancers. Some evidence of cross protection against HPV 31,45

Long term follow up Due to the long latency and the prolonged preinvasive phase after infection with HPV, many years of follow-up are needed for the ongoing trials to demonstrate a significant reduction in HPV-related cancers. Therefore, intermediate outcomes, such as decrease in precancerous lesions (ie, CIN), are considered acceptable surrogate end points for reduced incidence of cervical cancer.

Take home message Cervarix, gardasil, gardasil 9 9 – 15 yrs – 2 doses If dosage missed - upto 1 yr 2nd & 3rd doses can be given

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