Vaccination in cerical cancer
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"cervical cancer" AND "HPV vaccine"
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PMID: 40485552
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PMID: 41276263
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Vaccination in Cervical Cancer
Background: HPV and Cervical Cancer
Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HPV). HPV is endemic in the human population - approximately 50% of women become HPV-positive by age 24. Globally, cervical cancer is the fourth most common cause of cancer-related death in females worldwide, with around 500,000 new cases annually. HPV types 16 and 18 together account for ~70% of all cervical cancers.
- Roitt's Essential Immunology, p. 510
- Goldman-Cecil Medicine, HPV chapter
Types of HPV Vaccines
Three licensed HPV vaccines have been developed, all composed of non-infectious recombinant virus-like particles (VLPs) made from the HPV L1 capsid protein. VLPs are morphologically identical to native virions but contain no viral DNA, making them completely non-infectious yet highly immunogenic.
| Vaccine | Approved | HPV Types Covered | Common Name |
|---|---|---|---|
| Bivalent (2vHPV) | 2007 | 16, 18 | Cervarix |
| Quadrivalent (4vHPV) | 2006 | 6, 11, 16, 18 | Gardasil |
| 9-valent (9vHPV) | 2014 | 6, 11, 16, 18, 31, 33, 45, 52, 58 | Gardasil 9 |
- Types 6 and 11 cause genital/anogenital warts (condylomata acuminata)
- Types 16 and 18 are responsible for >70% of cervical cancers
- The additional types in 9vHPV (31, 33, 45, 52, 58) account for ~15% more cervical cancers
- Overall: 9vHPV can theoretically prevent over 90% of HPV-caused cancers
Currently in the United States, the bivalent and quadrivalent vaccines are no longer available; Gardasil 9 is the only HPV vaccine in use.
- Jawetz Melnick & Adelberg's Medical Microbiology, p. 2791
- Goldman-Cecil Medicine, p. 1574
- Harrison's Principles of Internal Medicine 22E, p. 557
Mechanism of Action
The L1 protein self-assembles into VLPs that trigger a strong neutralizing antibody response. This provides protection at mucosal and epithelial surfaces - the portals of HPV entry. The vaccines are prophylactic, meaning they prevent new HPV infections. They do not treat or clear existing HPV infections.
- Roitt's Essential Immunology, p. 510
- Goldman-Cecil Medicine, p. 1574
Efficacy
- For individuals not previously infected, the vaccine shows high efficacy in preventing persistent strain-specific HPV infections.
- Studies confirm prevention of preneoplastic lesions: cervical intraepithelial neoplasia (CIN) I, II, and III, as well as anal intraepithelial neoplasia (AIN).
- A landmark RCT showed the recombinant vaccine against HPV was 100% effective in preventing cervical cancer caused by HPV-16 and HPV-18.
- Real-world data from countries with high vaccine coverage show substantial decreases in oncogenic HPV type prevalence, high-grade cervical lesions, and cervical cancer incidence.
The most recent 2025 Cochrane Network Meta-Analysis (PMID: 41276263) including 60 RCTs with 157,414 participants found:
- In 15-25-year-old females: 30% reduction in CIN2+ regardless of HPV type (RR 0.70, 95% CI 0.56-0.88), and a 60% reduction in CIN2+ from vaccine-matched HPV types (RR 0.40, 95% CI 0.30-0.54) - both moderate-certainty evidence.
- In women over 25 years: little to no benefit compared with control.
A 2025 systematic review (PMID: 40485552) (54 studies) confirmed: countries with high vaccine coverage and routine programs show substantially decreased prevalence of oncogenic HPV types, high-grade cervical lesions, and cervical cancer.
Dosing Schedule (US Recommendations)
| Age at Initiation | Doses | Schedule |
|---|---|---|
| 9-14 years | 2 doses | 0 and 6-12 months |
| 15-26 years | 3 doses | 0, 1-2, and 6 months |
| Immunosuppressed (any age) | 3 doses | 0, 1-2, and 6 months |
| 27-45 years | Shared decision-making | Consider if not adequately vaccinated |
Emerging evidence from observational studies suggests similar efficacy with a single dose in young girls; a large randomized trial is ongoing comparing one vs. two doses.
- Harrison's Principles of Internal Medicine 22E, p. 557
- Goldman-Cecil Medicine, p. 1579
Target Population
- Primary target: Girls and boys aged 9-12 years (ideally before sexual debut and HPV exposure)
- Catch-up vaccination: All persons through 26 years of age
- Males: Added to vaccination recommendations in 2011 (prevents genital warts, anal cancer, and reduces community transmission)
- Immunocompromised individuals (e.g., HIV-positive, rheumatologic disease on immunosuppression): At increased risk of HPV and cervical cancer - require the 3-dose schedule
HPV vaccination should ideally occur before sexual activity begins, as the vaccines are not effective against already-established HPV infections.
Important Limitations
- Not therapeutic - vaccines do not treat existing HPV infection or cervical dysplasia.
- Incomplete coverage - vaccinated females must still continue Pap smear and HPV co-testing, as other HPV genotypes not included in the vaccine can cause cervical cancer.
- Duration of immunity - appears to extend for at least 10 years; long-term data are still accumulating.
- Reduced benefit in older women - women over 25 show little benefit from vaccination (Cochrane 2025).
Adverse Effects
-
Common (local): Injection site pain, redness, swelling
-
Common (systemic): Dizziness, syncope (especially in adolescents post-injection), nausea, vomiting, fatigue, headache, fever, urticaria
-
Rare, unconfirmed causal associations: Guillain-Barre syndrome, optic neuritis, transverse myelitis, rheumatoid arthritis - no confirmed causal link established
-
Goldman-Cecil Medicine, p. 1582-1584
Screening After Vaccination
Vaccination does not eliminate the need for cervical cancer screening. Current ACOG guidelines:
- Ages 21-29: Pap smear every 3 years (with reflex HR-HPV for ASCUS+)
- Ages 25-29: HR-HPV testing every 5 years is an acceptable alternative
- Ages 30-65: Cytology every 3 years, OR HR-HPV alone every 5 years, OR co-testing every 5 years
Summary
HPV vaccines represent one of the most successful preventive oncology interventions in history. The 9-valent vaccine (Gardasil 9) protects against the HPV strains responsible for over 90% of HPV-related cancers. Vaccination before sexual debut in the 9-14 age group with a 2-dose schedule is the most effective and cost-efficient approach. Combined with ongoing cervical cancer screening, it offers the realistic prospect of eliminating cervical cancer as a public health problem.
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