HPV Vaccine (9-valent)

The 9-valent HPV vaccine is a recombinant vaccine containing virus-like particles (VLPs) of the major capsid (L1) protein of nine HPV types. It provides protection against the HPV types responsible for the majority of HPV-related cancers and genital warts.

HPV Types Covered

High-risk oncogenic types (cancer-causing):

• HPV 16 and 18 — cause a large majority of cervical and anal cancers. Per the EMA EPAR, nearly 100% of cervical cancers are caused by HPV infection; approximately 90% of anal cancers, 15% of vulvar cancers, 70% of vaginal cancers, and 30–40% of penile cancers are also estimated to be caused by HPV.
• HPV 31, 33, 45, 52, and 58 — additional high-risk types responsible for approximately 20% of cervical cancers.
• Combined: covers approximately 90% of cervical cancers.

Low-risk types (cause genital warts):

• HPV 6 and 11 — cause most genital warts.

Mechanism of Action

All papillomaviruses have a shell, or capsid, made up of proteins called L1 proteins. Gardasil 9 contains the purified L1 proteins for the nine HPV types listed above, produced by recombinant DNA technology. The proteins are assembled into virus-like particles (VLPs) — structures that resemble HPV closely enough for the body to recognise them, but are not capable of causing infection or disease.

The vaccine also contains an aluminium-containing adjuvant to stimulate a stronger immune response. After vaccination, the immune system makes antibodies against the L1 proteins and is then able to produce them rapidly upon real-world exposure to HPV, preventing infection of epithelial cells and providing long-term immunological memory.

The vaccine does not treat existing HPV infection or HPV-related disease, does not protect against HPV types not included in the formulation, and does not replace cervical cancer screening.

Immunogenicity

• Seroconversion: >99% of recipients develop antibodies to all 9 HPV types.
• Peak antibody levels: 1 month after completing the vaccination series.
• Duration of antibodies: persists for at least 10–14 years (likely longer; studies ongoing).
• Antibody levels are higher than those produced by natural infection.

• Cervical intraepithelial neoplasia (CIN 2/3): 96–100% efficacy against CIN 2/3 caused by the additional five HPV types (31/33/45/52/58); near 100% against all 9 vaccine types combined.
• Vulvar and vaginal disease: 100% efficacy against high-grade VIN 2/3 and VaIN 2/3.
• Anal disease: 78–95% efficacy against anal intraepithelial neoplasia.
• Genital warts: >90% efficacy against warts caused by HPV 6 and 11.
• Real-world impact: in countries with high coverage, 75–90% reduction in cervical precancerous lesions, near-elimination of genital warts in young people, and meaningful herd protection in unvaccinated individuals.

For active immunization to prevent HPV-related cancers and precancerous lesions and genital warts in females and males.

In females (9–45 years): cervical, vulvar, vaginal, and anal cancers and precancerous lesions; cervical, vulvar, vaginal, and anal intraepithelial neoplasia (CIN, VIN, VaIN, AIN); genital warts.

In males (9–45 years): anal cancer and AIN; genital warts; expected prevention of oropharyngeal and other HPV-related head and neck cancers (data emerging).

Recommended Age Groups

• Routine: 11–12 years (can start at age 9).
• Catch-up: through age 26 years.
• Shared clinical decision-making: ages 27–45 years.

Optimal timing is before exposure to HPV (typically before sexual activity), but benefit exists even after sexual debut.

• Severe allergic reaction (anaphylaxis) to any vaccine component or to a previous dose of any HPV vaccine.

Defer vaccination for moderate or severe acute illness; pregnancy (defer until after delivery).

Not contraindications: minor illness, breastfeeding, immunosuppression, history of HPV infection or abnormal Pap test, history of genital warts, prior vaccination with a lower-valence HPV vaccine.

Generally well tolerated; most reactions are mild and temporary.

Very Common (>10%): injection site pain (up to 90%), swelling, redness, itching; headache; fatigue.

Common (1–10%): dizziness, nausea, low-grade fever, injection site bruising.

Uncommon (0.1–1%): syncope (particularly in adolescents — usually within 15 minutes of vaccination), urticaria, arthralgia, myalgia.

Rare (<0.1%): anaphylaxis, bronchospasm, angioedema.

Post-licensure surveillance has identified no signal of increased autoimmune disease, fertility problems, or adverse pregnancy outcomes when inadvertently administered during pregnancy.

• Other vaccines: can be given simultaneously at different injection sites — Tdap, MenACWY, hepatitis B, MMR, varicella, etc.
• Immunosuppressive therapy: may reduce immune response — vaccinate anyway and consider checking antibody titers.
• Hormonal contraceptives: do not reduce efficacy.

Dosing Schedule

Per the Gardasil 9 EPAR, the vaccine is given according to either a two-dose or three-dose schedule depending on age. Individuals who receive the first dose of Gardasil 9 should complete the regimen using this same medicine.

Age 9–14 years (two-dose schedule):

• Dose 1: initial visit (0 months).
• Dose 2: between 5 and 13 months after dose 1.
• (A three-dose schedule may also be used in this age group if preferred.)

Age 15 years and over (three-dose schedule):

• Dose 1: initial visit (0 months).
• Dose 2: 2 months after dose 1.
• Dose 3: 4 months after dose 2 (i.e. 6 months after dose 1).
• There should always be at least 1 month between doses 1 and 2 and at least 3 months between doses 2 and 3, with all doses given within 1 year.

Immunocompromised individuals: 3-dose schedule recommended regardless of age.

Route and Injection Site

Intramuscular injection only — preferably into the muscle of the shoulder (deltoid) or the thigh, per the EMA EPAR. Do not administer subcutaneously, intradermally, or intravenously.

Procedure

• Shake well before use (forms a white, cloudy suspension).
• Inspect visually — discard if discolored or contains particulate matter.
• Do not mix with other vaccines in the same syringe.

Syncope Prevention

Administer with the patient seated or lying down and observe for 15 minutes after vaccination, particularly in adolescents.

Interrupted Schedule

Continue the series — do not restart. Administer remaining doses with appropriate intervals.

Switching from other HPV vaccines: may complete the series with the 9-valent vaccine if started with a lower-valence formulation; follow the 3-dose schedule.

Pre-Vaccination Counseling

Counsel patients that the vaccine prevents the most common HPV-related cancers and genital warts but does not replace cervical cancer screening, does not treat existing HPV infection, and does not protect against all HPV types. Continue routine cervical cancer screening and safer sex practices.

Pregnancy and Breastfeeding

Defer vaccination until after pregnancy. If inadvertently administered during pregnancy, no intervention is needed and the pregnancy registry should be notified. Safe during breastfeeding.

Immunocompromised Patients

Safe to administer; may have reduced immune response. 3-dose schedule recommended for HIV-positive patients and others with immunocompromise. Ideally vaccinate before solid organ transplant or chemotherapy when possible.

Males and MSM

Vaccination is equally important for males — prevents anal cancer, genital warts, and reduces transmission. Particularly important for men who have sex with men (MSM), who have higher HPV-related cancer risk.

Allergy Notes

• Yeast allergy: not a contraindication for this vaccine (no yeast in formulation).
• Latex allergy: prefilled syringes may contain latex in the tip cap; vials do not.

Store at 2–8°C in the original package, protected from light. Do not freeze (discard if frozen). Brief temperature excursions (<25°C for <72 hours) are typically acceptable per local guidelines. Maintain cold chain during transport.

Before administration, remove from the refrigerator just before use, shake well to form a uniform white cloudy suspension, and discard if it cannot be resuspended.

3 years when stored properly at 2–8°C. Do not use after the expiry date.

Prescription required. Must be administered by qualified healthcare professionals in settings equipped to manage anaphylaxis.