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Vaccination for human papillomavirus (HPV) reduced the chances of developing invasive cervical cancer by almost 90% over an 11-year period, a Swedish study of almost 1.7 million girls and women showed.

Vaccinated women had a cervical cancer incidence of 47 per 100,000 persons as compared with 94 per 100,000 among unvaccinated women. After adjustment for all covariates, vaccination was associated with an incidence rate ratio (IRR) of 0.12 for women vaccinated before age 17 and 0.47 for women vaccinated from ages 17 to 30, reported Jiayao Lei, PhD, of Karolinska Institute in Stockholm, and colleagues in the .

"The greater risk reduction associated with younger age at initiation of vaccination is consistent with previous findings that showed a lower risk of genital warts and high-grade cervical lesions with HPV vaccination," the authors stated. "Our results also support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit, since vaccination has no therapeutic effect against preexisting HPV infection."

"Unvaccinated persons would from HPV vaccination if vaccination coverage of girls and women in a population exceeds 50%," they added. "A of HPV vaccination against genital warts has been observed previously in the Swedish population."

The study represents a major step forward in evidence supporting vaccine effectiveness, said Lois Ramondetta, MD, of the MD Anderson Cancer Center in Houston.

"The issue with looking at the effectiveness of vaccines is how long it takes to develop cervical cancer," Ramondetta told 番茄社区app. "All of the trials were based on looking at preventing infection from HPV, warts from HPV, and dysplasia from HPV. Never was the outcome cancer because it can take 10 years to develop cancer from HPV infection, whereas dysplasia takes maybe 3 to 5 years."

Prior to the study by Lei and colleagues, the only evidence of cancer prevention came from a of a medical journal and a study evaluating cancer incidence (not HPV-specific cancers) in females vaccinated at a young age, she added.

"[The Lei study] really is the first paper that correlated vaccination with reduction in [cancer] rate, so it does add a lot to what we know," said Ramondetta.

Previous studies of HPV vaccines showed protection against HPV infection and cancer surrogates, such as genital warts and high-grade precancerous cervical lesions. Pooled data from two randomized trials and a phase IV community-randomized study showed a reduction in HPV-related cancers, although overall cancer incidence was low (10 cases total) and not limited to cervical cancer, the authors noted.

Randomized, controlled trials cannot easily evaluate vaccination's protection against cervical cancer because of the long lead time from HPV infection to detection of invasive cervical cancer, they continued. As an alternative, investigators used data from Swedish demographic and health registries to examine the association between HPV vaccination and subsequent risk of invasive cervical cancer.

Sweden initiated a vaccination program for girls ages 13 to 17 in 2007, and in 2012 added a catch-up vaccination program for girls and women ages 13 to 18, as well as a school-based program for girls ages 10 to 12. Currently, Swedish women ages 23 to 64 are invited to participate in a national cervical cancer screening program. Registry data from those programs formed the basis for the analysis by Lei and colleagues, encompassing the years 2006 through 2017.

The analysis included 1,672,983 girls and women, ages 10 to 30, and with no prior HPV vaccination. Subsequently, 527,871 study participants received at least one dose of quadrivalent vaccine during follow-up and 1,145,112 did not get vaccinated.

The authors found that 19 participants in the vaccinated group had new diagnoses of invasive cervical cancer during follow-up as did 538 participants in the non-immunized group. An age-adjusted analysis yielded an IRR of 0.51 for the vaccinated population versus the unvaccinated group (95% CI 0.32-0.82).

Adjustment for calendar year and demographic and parental factors resulted in an IRR of 0.37. Adjustment for all covariates produced an IRR of 0.12 for women vaccinated before age 17, 0.47 for those vaccinated from 17 to 30, 0.36 for vaccination before age 20, and 0.37 for vaccination from ages 20 to 30. The 95% confidence intervals associated with the values did not include 1.00, making all of the results statistically significant.

"We are hoping this is the beginning of many papers like this, because we are now getting to that 10-year point with the vaccines" said Ramondetta, noting that the quadrivalent vaccine became available in 2006 and the nine-valent vaccine a few years later.

Prior to the COVID-19 pandemic, HPV vaccination rates in the U.S. had surpassed 50% for both sexes. Rates for all types of immunization have dropped substantially since early this year, and only time will tell whether HPV vaccination rates pick up again as the pandemic threat lessens, she said.

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