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Significant Decline in Precancerous Cervical Lesions in U.S.

The incidence of precancerous cervical lesions containing human papillomavirus (HPV) declined significantly from 2008 to 2014, as did the HPV strains that cause most cervical cancers, CDC investigators reported.

The number of cases of grade 2+ cervical intraepithelial neoplasia (CIN2+) reported to the CDC’s HPV Vaccine Impact Monitoring Project (HPV-IMPACT) decreased by 21%, and the proportion of specimens containing HPV16/18 decreased by a third. Declines were observed in all ages but the oldest age group (35-39), most of whom exceeded the age cutoff for vaccination.

The decline coincided with the introduction of the quadrivalent HPV vaccine, which targets HPV16/18, and the CIN2+ finding added to previous evidence suggesting a decrease in cervical precancerous lesions, reported Nancy McClung, PhD, RN, of the CDC in Atlanta, and colleagues, online in Cancer Epidemiology, Biomarkers & Prevention.

“Within eight years of HPV vaccine introduction in the United States, we report an overall declining trend in the proportion and estimated number of cervical precancers caused by HPV vaccine types among 18-39 year-old women,” the authors concluded. “The results of this analysis continue to support the high degree of effectiveness of the HPV vaccine in real-world settings and the rapid reduction of the HPV types that cause 70% of cervical cancers.”

The study also provided the first evidence that HPV vaccination leads to “herd protection,” as rates of HPV16/18-positive CIN2+ specimens declined in vaccinated and unvaccinated individuals alike.

In a separate study in The Lancet Oncology, an international group of scientists used statistical analyses to predict that cervical cancer could be essentially eradicated in most of the world by the end of the century with increased uptake of broad-spectrum HPV vaccines and widespread adoption of cervical cancer screening programs.

The CDC-led study focused on a time period that began 2 years after the first HPV vaccine was introduced in the U.S. and ended the year before the introduction of the nine-valent vaccine, now used exclusively in the U.S. The CDC recommends routine vaccination of girls, ages 11-12 years, and catch-up vaccination through age 26. A study conducted in 2016 showed that two thirds of girls, ages 13-17 years, had received at least one dose of HPV vaccine and half had received all recommended doses. As of 2015, more than 40% of women, ages 19-26 years, had received at least one dose of vaccine.

Previous studies showed declines in the incidence of cervical precancer since the introduction of the HPV vaccine, including one analysis showing a 56% decline among those ages 18-20 years and 39% among those ages 21-24 years. Seeking to add information about the impact of HPV vaccination, McClung and colleagues analyzed HPV-IMPACT data to determine trends in HPV16/18 presence in CIN2+ precancers.

The analysis included 10,206 specimens obtained across the study period and focused on women (ages 18-39) with specimens containing CIN2/3 or adenocarcinoma in situ (CIN2+) associated with HPV16/18. The proportion of HPV16/18-positive CIN2+ cases declined from 52.7% in 2008 to 44.1% in 2014 (P<0.001). Declines were observed in vaccinated (55.2% to 33.3%, P<0.001) and unvaccinated women (51.0% to 47.3%, P=0.03).

Subgroup analysis showed consistent declines in rates of HPV16/18-positive specimens by age group, diagnosis, and race/ethnicity:

  • Ages 18-20: 47.7% to 18.8% (P=0.02)
  • Ages 21-24: 53.8% to 44.0% (P<0.001)
  • Ages 25-29: 56.9% to 42.4% (P<0.001)
  • Ages 30-34: 49.8% to 45.8% (P=0.04)
  • CIN2: 40.8% to 29.9% (P<0.001)
  • CIN2/3: 61.8% to 46.2% (P<0.001)
  • Non-Hispanic whites: 59.5% to 47.9% (P<0.001)
  • Non-Hispanic blacks: 40.7% to 26.5% (P<0.001)

The primary limitation of the study was the inability to determine HPV vaccination status in about half of the women. Nonetheless, the authors found the results compelling.

“This is clear evidence that the HPV vaccine is working to prevent cervical disease in young women in the United States,” McClung said in a statement. “In the coming years, we should see even greater impact as more women are vaccinated during early adolescence and before exposure to HPV.”

The statistical modeling study of worldwide cervical cancer epidemiology followed a World Health Organization call for action to eliminate cervical cancer as a public health problem. The study in the The Lancet Oncology relied on cancer registry data collected by the International Agency for Research in Cancer. The primary objective was to determine an “elimination threshold” for cervical cancer, estimated from projected effects of “scaled-up” screening and vaccination programs, wrote Kate T. Simms, PhD, of the Cancer Council New South Wales in Sydney, and colleagues.

The analysis suggested that 44.4 million cases of cervical cancer would be diagnosed worldwide from 2020-2069 in the absence of any changes in the current status of surveillance and vaccination. Most of the cases would occur in low- and medium-resource countries. The authors projected that rapid scale-up of surveillance and vaccination (80%-100% global coverage) programs beginning in 2020 would avert 6-7 million cases over the same period, most of the effect occurring after 2060.

Rapid scale-up of prevention programs could reduce the incidence of cervical cancer to four new cases per 100,000 by 2059 for very highly developed countries, 2069 for highly developed countries, 2079 for medium-development countries, and 2100 or beyond for low-development countries. A cervical cancer incidence of less than six cases per 100,000 could be achieved by the end of the century, regardless of resource or development status, they concluded.

The study by McClung’s group was supported by the CDC. McClung and co-authors disclosed no relevant relationships with industry.

The study by Simm’s group was supported by the National Health and Medical Research Council (NMHRC) of Australia. Simms and several co-authors disclosed relevant relationships with the NMHRC, the VCS Foundation, and Roche Molecular Systems.