New Study From Scotland Supports the Effectiveness of HPV Vaccines to Prevent Cervical Cancer

The human papillomavirus (HPV) vaccine protects individuals from developing cervical cancer and other cancers caused by the virus, including vulvar, vaginal, anal, oropharyngeal (throat) and other head and neck cancers.[1] A recent large, long-term observational study conducted in Scotland adds to the evidence that HPV vaccination prevents the development of invasive cervical cancer and that even one or two doses of a bivalent (two-strain) vaccine administered one month apart are beneficial if given at 12 or 13 years or age.

Background on HPV and the vaccine

HPV is the most common sexually transmitted infection in the United States.[2] Approximately 43 million people in the United States, including 43% of adults aged 18-59, are infected by genital HPV. The HPV viral strains 16 and 18 are responsible for 70% of cervical cancer cases. In 2021, there were more than 14,480 new cervical cancer cases and 4,200 deaths.

In 2006, the Food and Drug Administration first approved a bivalent HPV vaccine. In 2014, the vaccine, which is now marketed as GARDASIL 9, was modified to protect against nine different strains of the virus. Collectively, these nine viral strains cause about 90% of cases of cervical cancer, genital warts and anal cancer.[3]

Since 2017, Gardasil 9 has been the only HPV vaccine available in the United States. In addition to preventing the cancers listed above, the vaccine is indicated in girls and women aged nine to 45 years for the prevention of genital warts and a variety of precancerous (dysplastic) lesions caused by the virus. In boys and men aged nine to 45 years, the vaccine is indicated for the prevention of anal, oropharyngeal and other head and neck cancers caused by HPV, as well as genital warts and precancerous lesions caused by the virus.

The Centers for Disease Control and Prevention (CDC) recommends that the HPV vaccine be administered in two doses over six to 12 months at ages 9-14 years or (for those not vaccinated earlier) in three doses over six months for teens and young adults (approximately ages 15-26 years). Only about 50% of U.S. adolescents are up to date on the HPV vaccine. A survey study published in 2018 found that laws promoting HPV vaccination using education, mandates or increased access in 24 states were not associated with changes in the frequency of intercourse or the use of condoms among sexually active adolescents.[4] For older, previously unvaccinated adults, the CDC recommends consultation with a medical professional because the vaccine may not be sufficiently beneficial to administer. Booster doses are not recommended. The HPV vaccine can be given on the same day as a COVID-19 vaccine.

The new Scottish study[5]

A 2024 observational study, published in the Journal of the National Cancer Institute in the United Kingdom, assessed the effectiveness of HPV vaccines for preventing new cases of invasive cervical cancer. Women born between 1988 and 1996 were retrospectively assessed using data obtained in 2020 from the Scottish cervical cancer screening system. The vaccination records were linked to cancer registry, immunization and regional social determinants data. Social determinants of health were assessed with the Scottish Index of Multiple Deprivation; scores ranging from 1 (most deprived) to 5 (least deprived) are based on regional income, employment, education, access to services, crime and housing.

Data from 447,955 individuals were reviewed with a mean follow-up period of approximately seven years. A two-strain HPV vaccine marketed as CERVARIX was used in Scotland from 2007 to 2012. The four-strain GARDASIL 4 vaccine was then used until 2023, when the nine-strain Gardasil 9 vaccine was introduced. All of these vaccines targeted HPV strains 16 and 18; most patients in the study received Cervarix, Gardasil 4 or no vaccine.

Invasive cervical cancer was identified in 234 individuals in the study. No individuals who received at least one vaccine dose between the ages of 12 and 13 years developed invasive cervical cancer (0 per 100,000). People immunized between the ages of 14 and 22 years and who received three doses of the HPV vaccine had 3.2 cases of invasive cervical cancer per 100,000, a rate that was significantly lower than for those who were unvaccinated (8.4 per 100,000).

The social determinants of health analysis found that the vaccine was effective across all five social deprivation levels but was especially important in the most deprived group. This analysis also showed that in unvaccinated women, the incidence of cervical cancer increased with increasing social deprivation.

The results of the Scottish study support the role of HPV vaccination in preventing invasive cervical cancer in women and the effectiveness of the vaccine at all levels of social deprivation. The findings add to the evidence that the vaccine is most effective if given at age 12 or 13 years. Strengths of the study are that it was population-based (all age-eligible women in Scotland included) and that it used individual-level data in the analyses.

Twenty-six previous randomized, controlled trials with a total of more than 73,000 participants support the efficacy and safety of HPV vaccines to prevent cervical cancer and precancerous lesions in women aged 15 to 26 years.[6] According to the prescribing information for Gardasil 9, the most common adverse reactions include injection-site pain, swelling or redness and headache.[7]

What You Can Do

As recommended by the CDC, the nine-strain HPV vaccine should be administered in two doses over six to 12 months at ages 9-14 years for both boys and girls. Parents and guardians with questions or concerns about the vaccine should discuss them with the child’s clinician. Receiving the HPV vaccine does not eliminate the need for cervical cancer and other cancer screening, though such screening may be required less often. Discuss the recommended cancer screenings and their timing with your clinician.
 

References

[1] Kaiser Family Foundation. The HPV vaccine: access and use in the U.S. July 12, 2021. https://www.kff.org/womens-health-policy/fact-sheet/the-hpv-vaccine-access-and-use-in-the-u-s/. Accessed April 2, 2024.

[2] Ibid.

[3] Palefsky JM. Human papillomavirus infections: epidemiology and disease associations. UpToDate. June 17, 2022.

[4] Cook EE, Venkataramani AS, Kim JJ, et al. Legislation to increase uptake of HPV vaccination and adolescent sexual behaviors. Pediatrics. 2018;142(3):e20180458.

[5] Palmer TJ, Kavanagh K, Cuschieri K, et al. Invasive cervical cancer incidence following bivalent human papillomavirus vaccination: a population-based observational study of age at immunization, dose, and deprivation. J Natl Cancer Inst. doi: 10.1093/jnci/djad263. Published online ahead of print January 22, 2024.

[6] Arbyn M, Xu L, Simoens C, Martin-Hirsch PP. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018;5(5):CD009069.

[7] Merck Sharp & Dohme. Label: human papillomavirus 9-valent vaccine, recombinant (GARDASIL 9). March 2024. https://www.fda.gov/media/90064/download. Accessed April 2, 2024.