HPV Vaccination: The Evidence Behind the Pathway

A mother brings her two daughters to the clinic after a school talk on cervical cancer. One is 12, the other 17. Neither is immunocompromised, and neither has had any HPV vaccine. The mother has heard that one injection is enough now. She wants to know whether that is true for both girls. This is an illustrative case, not a real patient.

By the end of this article you will know how many doses each girl needs, and why the answer is different for the two sisters.

1. Why Age Changes the Dose Count

“How can one dose do the work of three?” Because the immune system of a young adolescent answers this vaccine far better than an adult’s does. The tool used to give the reason in a paragraph:

The response to the HPV virus-like particles is strongly age-dependent. In early adolescence, 9 to 14 years, a naive immune system generates a strong B cell memory response, and the immunobridging trials showed that two doses in a 10 year old produce significantly higher antibody titres than three doses in a 20 year old. That finding set the reduced schedule.

Two terms in that paragraph need a word each. The vaccine is made of virus-like particles: the outer shell of the virus, with no DNA inside, so it cannot infect anyone. And an immunobridging trial compares antibody levels between groups rather than waiting years to count cancers. Suppose a younger group with fewer doses makes at least as much antibody as an older group with more. Then the protection shown in the older group can be carried across to the younger one.

Then came the evidence from India itself. A cohort of girls given one, two or three doses of the quadrivalent vaccine was followed for ten years:

The Indian cohort followed by IARC took it further. At ten years a single dose gave 95.4 per cent efficacy against persistent HPV 16 and 18 infection, against 93.1 per cent for two doses and 93.3 per cent for three.

IARC is the International Agency for Research on Cancer. One dose did as well as two or three. IAP ACVIP now recommends a single dose for immunocompetent girls from 9 up to 15 years, and the national programme launched on 28 February 2026 gives one dose.

2. The Two Sisters

“So both girls get one injection?” No. The 12-year-old does. Her sister of 17 does not. From 15 years, or at any age in a patient who is immunocompromised, the response no longer supports the reduced schedule, and the course is three doses at 0, 2 and 6 months. The two-dose schedule remains licensed, and it is what boys of the same age receive.

This is why the tool asks for the immune status before anything else. It changes the number of doses at every age.

3. “Is It Too Late for Her?”

The mother then asks about their cousin, who is 24. She has been married for three years, and her Pap smear last year was abnormal. Someone told her the vaccine is only for girls who have not started sexual life.

The tool calls this out as a practice advisory. A major barrier in India is withholding the vaccine from women who are already sexually active, or who have an abnormal Pap smear, assuming it is “too late”. This is clinically incorrect. The vaccine covers several oncogenic strains (16, 18, 31, 33, 45, 52, 58). Having met one of them is not the same as carrying all of them, and the protection against the rest is intact. She gains less than she would have gained at twelve. She still gains.

Her abnormal Pap needs its own work-up, which is in the cervical screening pathway.

4. Vaccination Does Not Replace Screening

“Once my daughters are vaccinated, they will not need the screening test, will they?” They will. The nonavalent vaccine covers the strains responsible for about 90% of cervical cancers. The other 10% are caused by types no current vaccine covers, and no schedule of doses will reach them. A fully vaccinated woman is therefore screened on the same interval as an unvaccinated one: by visual inspection with acetic acid under the national programme, or by cytology or HPV DNA testing where a laboratory is available. Nothing on her vaccination card moves that date.

The three vaccines available in India differ in what they cover:

5. The Larger Picture: 90-70-90

Each girl you vaccinate is part of a global plan. The tool used to set out the WHO targets as its section 5:

5. The WHO 90-70-90 Global Strategy

Three targets, to be met by 2030, for eliminating cervical cancer as a public health problem:

• 90 per cent of girls fully vaccinated with HPV vaccine by age 15.
• 70 per cent of women screened with a high-performance test by 35 years of age, and again by 45.
• 90 per cent of women identified with cervical disease receive treatment.

Notice that only the first target is about the vaccine. The other two are about screening and treatment. The strategy itself says what section 4 said: the vaccine alone will not eliminate cervical cancer.

6. The Common Mistake

The common mistake now runs the other way from the old one. For years the error was giving too few doses. Now that “one dose is enough” is in the newspapers, the risk is giving one dose to everyone. That includes the 17-year-old, the young woman and the girl on chemotherapy. It is easy to see why. The single dose is simpler, and it is true for most of the girls you will see. But it holds only for immunocompetent girls from 9 up to 15 years.

Back to Our Patients

The 12-year-old receives a single dose today. Her sister of 17 receives her first of three, with the second due at 2 months and the third at 6. Their cousin of 24 is offered the three-dose course as well, and her abnormal Pap is worked up on its own. All three are told the same thing about screening: the vaccine does not change the date.

Try This

A 13-year-old girl on treatment for acute lymphoblastic leukaemia is brought for HPV vaccine. Her mother asks for the single dose her friend’s daughter had. Illustrative case.

Answer. Three doses at 0, 2 and 6 months. At any age, a patient who is immunocompromised does not have the response that supports the reduced schedule.

Take-Home Points

• One dose for immunocompetent girls from 9 up to 15 years (IAP ACVIP; the national programme gives one).
• Two doses for boys of the same age.
• Three doses at 0, 2 and 6 months from 15 years, and at any age in immune compromise.
• Do not withhold the vaccine because a woman is sexually active or has an abnormal Pap: she still gains.
• A vaccinated woman is screened on the same interval as an unvaccinated one.

The rest of the childhood schedule is in the paediatric immunisation article, and the adult schedule in the adult immunisation article.

Declaration: the author built and maintains the tool. It is free to use. The figures in this article are those the tool carried in its Evidence tab on 5 November 2026, each from the source the tool names. The illustrative cases follow the tool’s rules; check the tool’s result for a real patient.

References

1. Shastri DD, Dhir SK, Rajsekhar B, et al. Indian Academy of Pediatrics (IAP) Advisory Committee on Vaccines and Immunization Practices (ACVIP): Recommended Immunization Schedule (2025) and Update on Immunization for Children Aged 0 Through 18 Years. Indian Pediatr. 2026;63:311-324.
2. World Health Organization (WHO). Human papillomavirus vaccines: WHO position paper, December 2022. Wkly Epidemiol Rec. 2022;97(50):645-672.
3. Press Information Bureau, Government of India. Cervical Cancer Vaccination Campaign Launched. New Delhi: PIB; 28 February 2026.
4. Basu P, Malvi SG, Joshi S, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol. 2021;22(11):1518-1529.
5. Ministry of Health and Family Welfare, Government of India. Operational Framework: Management of Common Cancers. New Delhi: MoHFW; 2016.
6. National Technical Advisory Group on Immunisation (NTAGI) 17th Meeting Recommendations (2022): HPV vaccine inclusion in the Universal Immunisation Programme (UIP). [The recommendation that preceded the programme. The programme itself launched on 28 February 2026.]
7. Merck Sharp & Dohme. GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant): prescribing information. Rahway, NJ: Merck; accessed 28 August 2026.
8. Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408.