A vaccine in childhood can prevent a cancer in adulthood

 Dr. A K Nanda        

MD, Radiation Oncology

Why are we discussing this?

• Cervical cancer is the fifth most common cancer in humans, the second most common cancer in women worldwide and the most common cause of cancer related death in the developing countries.
• The current estimates indicate approximately 1, 00,000 new cases diagnosed and 60,000 deaths annually in India. This death from cervical cancer is accounting to nearly 1/3rd of the global cervical cancer deaths.
• Estimates suggest that more than 80% of the sexually active women acquire genital Human Papilloma Virus (HPV) infection by 50 years of age. However, vast majority of the infections resolve spontaneously and only a minority (<1%) of the HPV infections progress to cancer.
• Sexually transmitted human papilloma virus (HPV) infection is the most important risk factor for cervical intraepithelial neoplasia (CIN) and invasive cervical cancer.
• In addition to cancer, HPV can also cause other health problems, such as genital warts.
• Prevalence of HPV among the cervical cancer cases is more than 90%. Hence through vaccination against HPV we can effectively prevent cervical cancer.

Human Papilloma Virus (HPV)

• They are small, non-enveloped DNA viruses.
• Over 100 serotypes of HPV have been discovered, out of which 15–20 can cause cancer.
• Out of these HPV serotypes 16 and 18 account for nearly 76.7% of cervical cancer in India.
• The interval between the oncogenic HPV infection and the invasive cervical cancer is 15–20 years.
• Non-cancer causing HPV serotypes-6 and 11 contribute over 90% of benign genital infections such as genital warts.
• Cancer causing HPV serotypes have also been associated with causation of anal, vulvar, vaginal, penile and oropharyngeal cancers.
• HPV infection is measured by means of HPV DNA detection in cervical cells (fresh tissue, paraffin-embedded or exfoliated cells).

Progression to cancer :

• HPV is a necessary cause of cervical cancer, but it is not a sufficient cause.
• Other causes which are necessary for HPV infection to progress to cancer are

1. Long-term use of hormonal contraceptives,
2. Multiple child birth
3. Early initiation of sexual activity,
4. Multiple sex partners,
5. Tobacco smoking and
6. Co-infection with HIV

• Other probable associated causes are

1. Co-infection with Chlamydia trachomatis bacteria and herpes simplex virus type-2
2. Immunosuppression
3. Low socioeconomic status
4. Poor hygiene 
5. Diet low in antioxidants

HPV Vaccine :

• Two vaccines licensed globally are available in India; a quadrivalent vaccine (Gardasil) and a bivalent vaccine (Cervarix).
• These vaccines are approved by the Drug Controller General of India (DCGI), US Food and Drug Administration, European Medicines Agency and prequalified by the World Health Organization.
• These vaccines do not protect against the serotype with which infection has already occurred before vaccination
• Gardasil is a mixture of proteins of HPV serotypes 16, 18, 6 and 11. This vaccine confers protection against both cervical cancer and genital warts.
• Cervarix is a mixture of proteins of HPV serotypes 16 and 18. This vaccine confers protection only against cervical cancer.
• Both vaccines available are equally efficacious and safe for protection against cervical cancer and precancerous lesions as of currently available data

Whether vaccine is a replacement for screening ?

• Vaccines are not 100% protective against cervical cancer and not a replacement for periodic screening. Hence, screening programs should continue as per recommendations.
• Both HPV vaccination and regular cervical screening together is the most effective way to prevent cervical cancer. Screening in cervical cancer is not discuss here and will be another topic in Oncogyan.

Recommendation :

• Because protection is seen only when the vaccine is given before infection with HPV, the vaccine should be given prior to sexual debut.
• The HPV vaccine is currently not licensed for use in female patients younger than 9 years or older than 26 years or for use in male patients.
• The Immunization schedule according to IAP is discussed here.

Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule :

• The Indian Academy of Pediatrics Committee on Immunization (IAPCOI) recommends offering HPV vaccine to all females who can afford the vaccine.
• It has introduced the vaccine at age group 11 and 12 in immunisation schedule.
• Also vaccination can be given to females as young as 9 years as well as in those aged 13–26 years who have not previously completed vaccination.
• Only 2 doses of either of the two HPV vaccines for adolescent/pre-adolescent girls aged 9-14 years. For two-dose schedule, the minimum interval between doses should be 6 months.
• For girls 15 years and older, and immunocompromised individuals 3 doses are recommended. For this 3 dose schedule, the doses can be administered at 0, 1-2 (depending on brands) and 6 months. Three doses schedule for Gardasil is 0, 2 and 6 months and for Cervarix is 0, 1 and 6 months.

Other facts about HPV vaccine:

• The vaccine dose is 0.5 mL given intramuscularly (IM), either in the deltoid muscle or in the antero-lateral thigh.
• HPV vaccines can be given simultaneously with other vaccines such as Hepatitis B and Tdap.
• At present, there is no data to support the use of boosters for HPV vaccine.

If vaccine schedule is interrupted :

• If the HPV vaccine schedule is interrupted, the vaccine series need not to be restarted.
• If the series is interrupted after the first dose, the second dose should be administered as soon as possible, and third dose to be administered with an interval of at least 12 weeks between the second and third doses.
• If only the third dose is delayed, it should be administered as soon as possible.

Cost :

• As of now HPV vaccine is introduced in Indian Academy of Pediatrics (IAP) immunisation schedule but not yet introduced in Universal immunisation programme(UIP). Hence this vaccine is not free in India. Everybody have to purchase it.
• The price of each dose of Cervarix is around Rs.2000/- and that of Gardasil is around Rs,3000/-.
• For reference I am giving the links for these two vaccines in website www.medlife.com . For Cervarix- click here For Gardasil- click here

Side effects :

• The most common adverse reactions are local reactions like pain, swelling with redness and systemic adverse effects such as fever (in only 10 to 20% cases).
• No serious vaccine-related adverse events have been reported till date.

Does HPV vaccine cause HPV infection?

• HPV vaccines are prepared from empty protein shells called virus-like particles (VLP) produced by recombinant technology. They do not contain any live biological product or DNA.
• Hence there is no risk of getting an HPV infection from the vaccine as the vaccine does not contain live virus.

Cautions during vaccination :

• The vaccine should be deferred in patients with moderate or severe acute illnesses.
• The patient should be observed for 15 min post-vaccination for syncope.
• The vaccine is not recommended for use in pregnant women. This is not due to adverse outcome of pregnancy, but due to limited data. Any exposure to the vaccine during pregnancy must be immediately reported.
• Lactating women and immunosuppressed female patients can receive the vaccine. The efficacy and the degree of immune response could be poor in the immunocompromised females.

Referrence

1.Cervical cancer in India and HPV vaccination, Kaarthigeyan, Indian Journal of Medical and Pediatric Oncology, 2012

2.HPV Vaccination of Girl Child in India: Intervention for Primary Prevention of Cervical Cancer, Asian Pacific J Cancer Prev. 2018

3.Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India, 2014