Human papillomas virus (HPV)Human papillomas virus (HPV) is a causative agent of skin and genital warts, laryngeal papillomatosis and cervical cancer. More than 100 types of papillomaviruses have been recognized on the basis of DNA sequence analyses, over 40 of which infect the genital area. Clinical manifestations with the most frequently associated HPV types include skin warts (types 1, 2, 3, and 10), recurrent respiratory papillomatosis (types 6 and 11), condyloma acuminata (types 6 and 11), and cervical cancer (types 16, 18, 31, 33, and 45).
Disease burden of cervical cancerHPV types 16, 18, 31, 33, and 45 are responsible for 90% of invasive cervical cancer in India. Invasive cervical cancer (ICC) is the second most common cancer among women worldwide, with an estimated incidence of 493,000 new cases and mortality of 274,000 each year (1,2). Cervical cancer is the leading cause of death in middle aged Indian women. In India, there are an estimated 132,000 new cases and 74,000 deaths each year due to cervical cancer. Vaccination against high-risk HPV types could substantially reduce the incidence of cervical cancer.
Types of HPV vaccineTwo types of HPV vaccines are available. Both vaccines contain HPV major capsid protein L1, which self assemble to form empty virus like particle (VLP) without nuclear DNA. This does not induce infection but trigger immune cell to produce antibodies.
1. Quadrivalent vaccine: It contain a protein mimic of the L1 outermost protein capsid (VLPs) specific to the two most common HPV types causing cervical cancer HPV-16 and -18. also HPV-6 and 11, the most common HPV types causing genital warts
2. Bivalent vaccine: contain L1 protein (VLPs) specific two HPV-16 &18.
Both vaccines do not protect against the serotype with which infection has already occurred before vaccination.
Both vaccines safety and efficacy is proven in various clinical trials. Quadrivalent vaccine with 3 doses has shown 99% efficacy at a median follow up of 3 years against 16 & 18 related cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ (AIS). Additionally 99-100% efficacy was seen against vaccine type related genital warts, vaginal intraepithelial neoplasia (VaIN) and vulvar intraepithelial neoplasia (VIN). Follow up studies in subset of participant over 5 years show persistent protection and good response to booster immunization indicative of immune memory. Bivalent vaccine has shown 100% efficacy against CIN 2+ lesions associated with HPV-16 and HPV-18 up to 6.4 years of follow-up. Cervarix has demonstrated type-specific protection against the five most frequent cancer-causing HPV types (16, 18, 31, 33, and 45) that are responsible for 82% of invasive cervical cancer globally.
Side EffectsBoth vaccines have good safety profile and only cause mild local reaction like pain, swelling, erythema in 10-20% of recipients. Systemic side effects are usually nil in immediately post vaccination but few may complaint of myalgias, arthralgias, headaches and gastrointestinal symptoms after vaccination in 30 days follow up.
Cross ProtectionHPV-18 and 45, along with HPV-16, are found in over 90% of endocervical adenocarcinomas. Other oncogenic HPV types account for almost all the remainder cancers. Importantly, HPV-31, 33 and 45 account for approximately 12% of cervical cancers. Both vaccines have shown some evidence of cross protection against HPV31 and HPV45, closely related HPV types to HPV16 and 18.
ScheduleVaccination should be initiated before sexual debut. It is recommended to start vaccination at 10-12 years of age but catch up vaccination is permitted up to 45 years also. Both vaccines require 3 doses.
Quadrivalent vaccine is recommended at 0, 2 and 6 months (minimum interval between 1st and 2nd dose is 4 weeks and second and third dose is 12 weeks). Bivalent vaccine is schedule as 0, 1 and 6 months.
HPV vaccine can be administered along with HBV and Tdap vaccine without loss of efficacy.
HPV vaccine is only preventive and does not cure HPV disease once infection has occurred. Hence it's very important that it is given before the sexual debut i.e. adolescence.
Vaccination in malesThe potential benefits of vaccinating males include direct protection against genital warts, anal and penile cancer and precancerous lesion (especially in gay couples) and indirect protection of women by reducing the transmission of HPV infection. Studies are underway to determine these aspects of vaccination. US FDA and UK have already licensed HPV vaccine for this purpose. Results of dynamic simulation models of HPV transmission suggest that if high coverage of females can be achieved, there is little additional reduction in cervical cancer to be gained by vaccinating males.
Can HPV vaccine be given to individual with previous HPV infection?Studies have shown that there may be some benefit in vaccination for women with early infection or early natural history of disease. It may not cure the disease and long term protection is yet to determined.