Gardasil 9 broadens HPV vaccine protection

Historical milestone — this page describes an event dated 2014. It is not current breaking news.

Nine types instead of four

Human papillomavirus is not one virus. NCI counts more than 200 related types, of which more than 40 spread through direct sexual contact. About a dozen of those can cause cancer.

The first HPV vaccine covered four types. In December 2014 the FDA licensed Gardasil 9, a nine-valent vaccine covering types 6, 11, 16, 18, 31, 33, 45, 52 and 58. FDA review documents for the application, STN 125508, carry an action due date of December 10, 2014.

The five added types are the point. NCI describes what each group does:

• Types 6 and 11 cause 90 percent of genital warts.
• Types 16 and 18 cause about 70 percent of cervical cancers, and a higher share of some other HPV-caused cancers.
• Types 31, 33, 45, 52 and 58 account for a further 10 to 20 percent of cervical cancers.

The trial behind the license

The efficacy study was V503-001, a randomized, double-blinded, phase 2b/3 trial. The comparator was not a placebo. It was the existing four-type vaccine, which is a harder test.

It randomized 14,215 women aged 16 through 26 from five continents and 18 countries. Half received the nine-type vaccine, half the four-type one. Both were given as three injections into muscle, on day one and at months two and six. Median follow-up was about 40 months.

The trial could not simply repeat the old vaccine's work. For the four original types, the FDA accepted immunobridging: showing the new vaccine produced antibody levels no worse than the old one, and inferring the same protection. Antibody ratios between the two vaccines ranged from 0.80 to 1.19, clearing the pre-set bar.

For the five new types, real efficacy was measured. The endpoint was high-grade precancerous lesions of the cervix, vulva and vagina caused by types 31, 33, 45, 52 and 58.

Efficacy in the per-protocol population was 96.7 percent, with a 95 percent confidence interval of 80.9 to 99.8 and a p-value below 0.0001. The FDA's success criterion was a lower bound above 25 percent, so this cleared it by a wide margin. Across subgroups by age, race, region, ethnicity, contraception use and number of partners, efficacy ran from about 87 to 100 percent.

There were downstream effects too. The vaccine cut the proportion of women needing a genital biopsy by 31.3 percent, and the proportion needing definitive treatment for a lesion by 46.5 percent.

How the vaccine actually works

The vaccine contains virus-like particles. These are made from HPV surface proteins that assemble into shells resembling the outside of the virus, but with no viral DNA inside. They cannot infect anything.

The immune system responds to the shape and makes antibodies. On a later real encounter, those antibodies bind the virus and stop it entering cells.

This is why the timing matters so much. The vaccine prevents infection; it does not clear one. NCI is explicit that it does not treat existing HPV infection or HPV-caused disease.

What is now recommended

The FDA licence covers girls and women, and boys and men, aged 9 through 45.

NCI reports that CDC recommends HPV vaccination routinely at age 11 or 12, and says it can start at age 9. It is recommended for everyone through age 26 who was not adequately vaccinated earlier.

For adults aged 27 through 45 the picture is different. NCI notes the vaccine is FDA-approved to that age but not routinely recommended there, because more people in that age band have already been exposed. It is a conversation rather than a default.

Vaccination should be delayed until after pregnancy, though NCI states there is no evidence it harms a pregnancy or a fetus.

When to get checked

Vaccination does not replace screening. NCI is direct about this: because the vaccine does not cover every cancer-causing HPV type, vaccinated women should follow the same screening schedule as everyone else. Our page on cervical cancer screening sets out what those tests are and when they happen.

Symptoms are the second track. Early cervical cancer often causes none, which is exactly why screening exists. Bleeding between periods, bleeding after sex, bleeding after menopause, unusual discharge, or pelvic pain all warrant an appointment. Most turn out to be something else, as our page on cervical cancer symptoms explains.

An abnormal screening result is not a cancer diagnosis. It is a reason for a closer look. Our page on cervical cancer explains what the follow-up steps involve.

The numbers this was aimed at

The American Cancer Society projects 13,490 new US cervical cancer cases and 4,200 deaths for 2026, and SEER reprints those two estimates. Median age at diagnosis, measured by SEER itself, is 50, and the disease is most often diagnosed between 35 and 44.

Five-year relative survival for cases from 2016 to 2022 is 68.8 percent overall. By spread at diagnosis it is 91.8 percent while confined to the cervix, 64.0 percent with regional lymph nodes involved, and 20.5 percent for distant disease. Forty-one percent are found localized.

These are group figures from a registry, not a forecast for any individual. What they show is the size of the gap that catching disease early, or preventing it outright, is meant to close.

NCI's estimate of what widespread vaccination could achieve is a reduction in cervical cancer incidence worldwide of as much as 90 percent, and it notes that US cervical cancer incidence has already declined.

What to keep in perspective

The five extra types are not all the remaining risk. Types outside the vaccine still cause a share of cervical cancers, which is the whole reason screening continues.

The efficacy figure comes from the per-protocol population: women who completed the schedule and were not already infected with the relevant types. Real-world protection in a partly vaccinated, partly exposed population is a different measurement.

Efficacy against anal disease from the five new types was not directly measured. Cases were too rare in the trial, so the FDA accepted inference from genital lesions, antibody data and prevention of persistent infection.

And a 2014 licence is a starting point. Dosing has since changed, with two doses licensed for younger recipients and three for older ones, and NCI reports evidence that one dose gives protection not inferior to two.

Sources

• FDA, GARDASIL 9 product page (STN 125508, Merck Sharp & Dohme) — https://www.fda.gov/vaccines-blood-biologics/vaccines/gardasil-9
• FDA Center for Biologics Evaluation and Research, Clinical Review, STN 125508/0, GARDASIL 9 — https://www.fda.gov/media/106858/download?attachment
• NCI, Human Papillomavirus (HPV) Vaccine fact sheet — https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-vaccine-fact-sheet
• SEER Cancer Stat Facts, Cervical Cancer — https://seer.cancer.gov/statfacts/html/cervix.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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