HPV Vaccine Seen Slashing Abnormal Cytology in Girls


From the Lancet

The incidence of high-grade cervical abnormalities has dropped by more than a third among teenage girls since the start of a school-based vaccination program, according to a study by Australian researchers.

The population-based study, published online in the Lancet, examined data from a cervical-screening program in Victoria, Australia's second largest state (Lancet 2011;377:2085–92).

Dr. Julia Brotherton of the Victorian Cytology Service Registries in East Melbourne, which collects data on more than 99% of cervical cytology on the state's girls and women, led the research.

Dr. Brotherton and her colleagues noted a decline in cervical abnormalities within 3 years after the initiation of widespread vaccination against human papillomavirus (HPV) among girls aged 18 years and younger.

In older age groups, there were no declines.

Vaccination records were not linked to screening data in the study by Dr. Brotherton and her colleaguesí However, three-dose coverage with the quadrivalent HPV vaccine (Gardasil) is currently estimated at 79% for girls in the first year of high school, and 71% for girls in the last year of high school in Victoria, where the program began in 2007.

The recommended initial screening age for cervical disease is 18 years in Australia; however, some younger girls are screened at the discretion of their health care providers.

After comparing screening results for girls aged 18 years and younger who were screened between 2003 and mid-2007 and between mid-2007 and 2009, after the vaccination program began, the investigators found that the incidence of high-grade abnormalities – cervical intraepithelial neoplasia (CIN) of grade 2 or worse, or adenocarcinoma in situ – dropped from 0.80% (109 of 13,620 girls screened) to 0.42% (23 of 5,538).

The finding, they wrote, “reinforces the appropriateness of the targeting of prophylactic HPV vaccines to pre-adolescent girls.”

The researchers also looked at low-grade abnormalities that were reported through cervical screening, and both low- and high-grade abnormalities in women who were older than 18 years of age.

Only women who were younger than 18 years saw improvement in high-grade abnormalities, and no significant decline was noted for low-grade abnormalities in any age group.

In an accompanying editorial, Dr. Mona Saraiya and Susan Hariri, Ph.D., of the Centers for Disease Control and Prevention, urged caution in interpreting the findings.

They said that a demonstrable reduction of the burden of cervical cancer (the main goal of HPV vaccination) will require much more data and several decades to establish.

“The not-so-cautious optimist in us wants to hail this early finding as true evidence of vaccine effect,” Dr. Saraiya and Dr. Hariri wrote. “However, individual-level vaccine status was not considered – as it perhaps should have been in view of the availability of such data in Victoria.”

The findings may have been affected by health care providers' screening and managing vaccinated patients less aggressively, “especially girls younger than the recommended screening age of 18 years,” Dr. Saraiya and Dr. Hariri argued.

Additionally, “with the almost 40% decrease in the incidence of high-grade cervical abnormalities recorded in girls younger than 18 years, a similar though smaller decrease would be expected in girls in the next oldest age group (those aged 18–20 years), who were likely to benefit from the vaccine and in whom vaccine coverage was high,” Dr. Saraiya and Dr. Hariri wrote.

However, the study found no decrease in this oldest age group.

Dr. Brotherton and her coinvestigators acknowledged that the population-based study design was a weakness, and they noted that further studies linking vaccination and cytology data would be needed to confirm the findings of their study.

However, they wrote, “we believe that our findings have strong biological plausibility and that the specific temporal association, differential by age (which is related to both coverage and likelihood of sexual activity and therefore HPV exposure before vaccination), suggests that the vaccination program caused the decrease.”

Human papillomavirus types 16 and 18 can often cause high-grade abnormalities less than a year after infection, they noted.

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