Vaccine Against HPV Strain Protects Against High-Grade Cervical Neoplasia

Paula Moyer, MA

November 03, 2004

Nov. 3, 2004 (Washington) — A vaccine against human papillomavirus 16 (HPV 16) has 100% vaccine efficiency against cervical intraepithelial neoplasia (CIN) at stages 2 to 3, according to investigators who presented their findings here at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy.

"Although there are more than 30 HPV types, HPV 16 causes approximately half of cervical cancer in the world," principal investigator Connie Mao, MD, said in an interview with Medscape. "The vaccine against HPV that we studied is highly effective against CIN 2-3, the precursor [of cervical cancer]. Among those vaccinated, none developed CIN 2-3 compared with 12 such cases in the placebo group." Dr. Mao is an attending physician in obstetrics and gynecology at Harborview Medical Center in Seattle, Washington, where she is also an assistant professor of obstetrics and gynecology at the University of Washington.

The investigators were interested in testing the vaccine's potential to protect against CIN 2-3 because an earlier study had shown that the vaccine protected against persistent HPV infection, a known cause of CIN 2-3. They wanted to find out if the vaccine would go on to prevent HPV 16–related CIN 2-3 and therefore provide more long-term protection against cervical cancer.

Therefore, the investigative team randomized 2,391 women aged 16 to 23 years to receive three doses of placebo or a vaccine consisting of HPV 16 virus-like particles (VLP). The vaccine, given in 40-µg doses, was administered at day 0 and then at month 2 and month 6. The investigators also obtained genital samples for HPV 16 DNA at day 0, month 7, and then every six months through month 48; the participants also underwent a Pap test at those visits.

The analysis population included women who completed the entire vaccine regimen, were negative for HPV 16 through month 7, and completed at least one additional visit. Patients underwent colposcopies and cervical biopsies as clinically indicated.

Of the 750 placebo recipients who met the criteria for evaluation, the investigators documented 12 cases of HPV 16–related CIN 2-3, six of which were CIN 2 and six of which were CIN 3. Of the 755 vaccinees, no such events were observed, for a vaccine efficiency of 100% (95% confidence interval [CI], 65% - 100%).

Through the end of the study, 111 subjects in the placebo group developed persistent HPV 16 infection compared with seven subjects in the vaccination group, for a vaccine efficacy of 94% (95% CI, 88% - 98%). After immunization, HPV 16 antibody titers peaked at month 7 (GMT 1519 mMu/mL) and declined through month 18 (GMT 202 mMu/mL). The titers remained relatively stable from month 30 through the study's end (GMTs range, 128 - 150 mMu/mL).

"After three and a half years of follow-up, we concluded that the vaccine was able to prevent clinical cervical disease," Dr. Mao said. "That's the first time that's been done in a human study. The next step will be to complete phase 3 trials of an ongoing study of a quadrivalent HPV vaccine, which also looks at men and children. If the vaccine is safe and effective, it would make sense to immunize children and young adolescents before they become sexually active." Men are being studied for the quadrivalent vaccine because HPV is sexually transmitted, Dr. Mao said.

"This is a tremendously important study because it had such dramatic results," said John Zaia, MD, who was not involved in the study. "Taking an immune function of the body and preventing a neoplastic change is a major advance. If this holds true, that we would vaccinate women universally at puberty against human papillomavirus, we could eliminate the most common cause of cervical dysplasia." Dr. Zaia is chief of infectious disease at City of Hope Cancer Center in Duarte, California.

"This development could raise the question of how to change the whole medical establishment and cause it to move from surveillance to prevention," Dr. Zaia said. "HPV is a very important virus that gets very little press, but I think this study should get a lot of attention."

The study was funded by Merck & Company, Inc., which manufactures the vaccine.

44th ICAAC: Abstract 3741. Presented Nov. 1, 2004.

Reviewed by Gary D. Vogin, MD

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