Recommendations for UseCervical cancer is responsible for significant morbidity/ mortality in Indian women and affects women of all socio economic strata. Compliance with cervical Papanicolou (PAP) smear screening is low in India. The currently available vaccines are safe and efficacious. The HPV vaccines are thus of public health importance. The IAPCOI recommends offering HPV vaccine to all females who can afford the vaccine (Category 2) in the schedules discussed below. Since protection is seen only when the vaccine is given before infection with HPV, the vaccine should preferably be given prior to sexual debut. The vaccine should preferably be introduced to parents as a cervical cancer preventing vaccine and not as a vaccine against a sexually transmitted infection (STI). Vaccines are not 100% protective against cervical cancer and not a replacement for periodic screening. Hence screening programs should continue as per recommendations. Need for boosters and potential for serotype replacement would be known in future. Both the available vaccines are equally efficacious and safe for protection against cervical cancer and precancerous lesions as of currently available data. The quadrivalent vaccine additionally protects against anogenital warts. |
Dose and ScheduleThe vaccines should be stored at 2 to 8° C, must not be frozen and protected from light. The dose is 0.5 ml intramuscular in deltoid. The recommended age for initiation of vaccination is 10-12 years. As of current licensing regulations in India, catch up vaccination is permitted up to the age of 26 years. Three doses at 0, 2 and 6 months are recommended with Gardasil TM (minimum interval between 1st and 2nd dose is 4 weeks and second and third dose is 12 weeks) and 0, 1 and 6 months with Cervarix TM. HPV vaccines can be given simultaneously with other vaccines such as hepatitis B and Tdap. As a precaution against syncope following any vaccine in adolescents, the vaccinee should be counseled prior to vaccination, vaccine be administered in a sitting/lying down position and the patient observed for 15 minutes post vaccination. Both vaccines are contraindicated in those with history of previous hypersensitivity to any vaccine component and should be avoided in pregnancy. The vaccines may be administered in the immunocompromised but immunogenicity and efficacy may be lower. At present there is no data to support use of boosters. |
Globally, cervical cancer is the second most common cancer in women with approximately 5,00,000 cases annually and 350,000 deaths. Additionally, cervical cancer may occur early and strike at the productive period of a woman’s life. It is well recognized that HPV is a necessary cause of cervical cancer. 100 serotypes of HPV have been discovered of which 15-20 are oncogenic. Types 16 and 18 account for 70% of the cases of invasive cervical cancer globally. The lag period between infection with oncogenic HPV and invasive cervical cancer is 15-20 years. Oncogenic HPV serotypes have also been implicated in causation of anal, vulvar, vaginal, penile and oropharyngeal cancers.
Additionally, non-oncogenic HPV serotypes 6 and 11 are responsible for more than 90% of anogenital warts and most recurrent respiratory papillomatosis. Data from national cancer registries in India indicate that cervical cancer is the most common cancer/cause of cancer related death in Indian women. Approximately 1,32,000 cases occur annually with 74,000 deaths. Indian women face a 2.5% cumulative lifetime risk of cervical cancer and 1.4% cumulative risk of death from cervical cancer. HPV types 16 and 18 account for 76.7% of cervical cancer in India. There is no data on burden of anogenital warts in the general community; warts have been reported in 2-25.2% of STI clinic attendees in India.
Two vaccines have been licensed globally; a quadrivalent vaccine marketed as Gardasil TM and the other a bivalent vaccine marketed as Cervarix (TM). Both are manufactured by recombinant DNA technology that produces non-infectious virus like particles (VLP) comprising of the HPV L1 protein, the major capsid protein of HPV. Clinical trials with both vaccines have used efficacy against cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ (AIS) caused by HPV strains contained in the concerned vaccine as primary end points. Both vaccines do not protect against the serotype with which infection has already occurred before vaccination. Both vaccines have been licensed in several countries world over.
Gardasil (TM) now available in India is a mixture of L1 proteins of HPV serotypes 16, 18, 6 and 11 with aluminium containing adjuvant. Clinical trials with three doses at 0, 2 and 6 months in more than 16,000 women aged 16-26 years from 5 continents including Asia have shown 99% efficacy at a median follow up of 1.9 years against types 16, 18 related CIN- 2/3 and AIS in per protocol analysis (women who received all three doses of the vaccine and who remained uninfected with vaccine HPV type at onset and for 1 month after completion of the vaccine schedule). 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 a subset of participants over 5 years show persistent protection, and good response to booster immunization indicative of immune memory. Immunogenicity studies in females 9-15 years showed antibody titers non-inferior to those aged 16-26 years. Local adverse effects reported were pain at the injection site in 83% of vaccinees (mainly mild–moderate intensity) and swelling and erythema in 25%. Systemic adverse effects such as fever reported in 4% of vaccines. No serious vaccine related adverse events have been reported either in trials or post marketing surveillance studies.
Cervarix TM is a mixture of L1 proteins of HPV serotypes 16 and 18 with ASO4 as an adjuvant. Clinical trials with three doses at 0, 1 and 6 months in more than 18000 women globally has shown 90% efficacy against type 16/18 related CIN2/3 and AIS at 15 month follow up in modified intention to treat analysis (included women who were at baseline negative for HPV DNA of vaccine type virus and who received at least 1 dose of the vaccine). Follow up studies in a subset of participants over 4-5 years show no evidence of waning immunity.
Local side effects reported were pain (mild and
moderate intensity) in 90% and swelling and erythema in 40%.
Systemic side effects such as fever were seen in 12%. No serious
vaccine related adverse effects were observed.