Early HPV vaccination leads to better protection


Getting the HPV vaccine after the age of 18 leads to similar outcomes with no vaccination at all, according to investigators.

Women at or above 18 without cervical abnormalities at vaccination had a 23% reduction in the risk of high-grade squamous intraepithelial lesions (HSIL) as compared with unvaccinated women. The quadrivalent vaccine did not appear to protect against HSIL among women who had abnormal cytology at the time they were vaccinated, they reported online in the Journal of Clinical Oncology.

"A significant percentage of vaccinated women may not be protected against HSIL or lesser dysplasia especially if they were vaccinated at older age or had abnormal cytology before vaccination," Salaheddin M. Mahmud,MD, PhD, of the University of Manitoba in Winnipeg, and colleagues concluded.

"These findings affirm the importance of vaccination before any significant exposure to HPV occurs and underscore the need for screening programs that cover all sexually active women, even if they were vaccinated," they wrote.

The quadrivalent HPV vaccine has been shown to reduce the risk of cervical cancer, which evolves from infection with HPV 16 and 18 in 70% of cases worldwide. Whether the vaccine protects against cervical dysplasia had been been studied by use of population-based individual-level data, the authors noted in their introduction.

To examine HPV vaccine effectiveness against cervical dysplasia, Mahmud and colleagues reviewed records for 3,541 females vaccinated at age ≥15 in Manitoba from September 2006 to April 2010. Each vaccinated patient was matched with three unvaccinated patients.

Investigators calculated hazard ratios for three outcomes: atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), and HSIL.

During a median follow-up of 3.1 years, vaccinated patients had LSIL and HSIL rates of 3.3% and 2.3%, respectively, compared with 3.7% and 2.6% for unvaccinated patients. No patient (vaccinated or not) developed cervical cancer during follow-up, but 12 vaccinated patients (0.3%) and 22 unvaccinated patients (0.2%) developed carcinoma in situ.

Investigators analyzed the data by age group and history of abnormal cervical cytology. Vaccine effectiveness varied by both factors.

Among girls ages 15 to 17 at enrollment, vaccine effectiveness estimates were 35% against HSIL, 21% for LSIL, and -1% for ASCUS. Exclusion of girls who did not have at least one Pap test after enrollment resulted in higher estimated effectiveness: 46% against HSIL, 35% against LSIL, and 23% for ASCUS.

For patients who were at or above 18, and had no history of abnormal cytology before enrollment, estimated effectiveness rates were 23% of HSIL, -18% for LSIL, and -20% for ASCUS. A history of abnormal cytology reduced the estimates to -8% for HSIL, 37% for LSIL, and 56% for ASCUS but with wide confidence intervals.

Exclusion of women at or above 18 years old who did not have at least one Pap test after enrollment resulted in estimated vaccine effectiveness rates of 35% for HSIL, 2% for LSIL, and -5% for ASCUS in the subgroup who had no history of abnormal cytology before enrollment and rates of -33%, 25%, and 53% for those with a history of abnormal cervical cytology.

"Postmarketing epidemiological studies are needed to evaluate the real-life effectiveness of the HPV vaccines and to monitor their impact on other preventive measures such as screening and sexually transmitted infection control programs," the authors concluded.

The findings confirm data from previous studies showing that HPV vaccine is less effective in older teens and young women, said Ronald Alvarez, MD, PhD, of the University of Alabama at Birmingham.

"We know that this group of women is more likely to have had exposure to human papillomavirus and perhaps even had some disease," Alvarez told MedPage Today. "In that setting, we know that the HPV vaccine is less likely to be effective."

HPV vaccine will be most effective when three criteria are met, said Krishnansu Tewari, MD, of the University of California Irvine.

  1. No high-risk vaccine-specific HPV DNA on the cervix at the time of vaccination
  2. No antibodies against the high-risk vaccine-specific HPVs in the serum of the patient at the time of vaccination
  3. The patient’s cervical cytology is, and has been normal at the time of vaccination

“It is so important that males and females are vaccinated as early as possible, before the so-called sexual debut -- before they start having sex,” Tewari said in an email. “It doesn’t surprise me that women vaccinated after age 18 had less protection in this study. In the U.S. the vaccine has been approved beginning at age 9.”


Source: MedPage Today: http://www.medpagetoday.com/HematologyOncology/OtherCancers/43674

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