Gardasil 96% Effective Against Premalignancies

CHICAGO — The quadrivalent human papillomavirus vaccine, which protects women against HPV types 6, 11, 16, and 18, also prevents the abnormal growth of precancerous cells in the cervix associated with these four types.

This finding, from the international phase IIb/III Quadrivalent HPV Vaccine Study, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

These premalignancies, known as cervical intraepithelial neoplasia (CIN), are a major contributor to health care costs resulting from screening, research, and treatment, Dr. Sven-Eric Olsson said at the conference, which was sponsored by the American Society for Microbiology.

Through 3 years of follow-up, the vaccine was 96% effective in preventing CIN related to HPV types 6, 11, 16, and 18, and vaccine efficacy was significant for all four of the HPV types, though somewhat less so for HPV 11, said Dr. Olsson, with the Karolinska Institute at Danderyds Hospital in Stockholm.

The Food and Drug Administration-approved quadrivalent HPV vaccine (Gardasil; Merck & Co.) is recommended by the Centers for Disease Control and Prevention for use by women aged 9-26 years. The four targeted HPV types are responsible for 70% of cervical cancers and 90% of genital warts, according to the CDC.

The investigators drew data from more than 18,000 women aged 16-26 years who were enrolled in one of three randomized trials sponsored by Merck.

The cohort of women was evenly divided to receive either vaccine or placebo at day 1, month 2, and month 6. Subjects underwent cervicovaginal sampling at day 1 and month 7 and Pap testing at day 1 and 6- to 12-month intervals for up to 48 months.

All of the specimens were HPV typed and histologically diagnosed by a four-member blinded pathology panel, said Dr. Olsson. He has given lectures for Merck but has no financial stake in either Merck or GlaxoSmithKline, which has filed with the FDA for approval of Cervarix, a bivalent HPV vaccine protecting against types 16 and 18.

Primary per protocol vaccine efficacy analysis included subjects who received all three of the doses, were sero- and PCR-negative to the four HPV types at day 1 and PCR-negative through month 7, and had no major protocol deviations.

Dr. Olsson reported that in the group that received the vaccine, there were 6 cases of HPV 6/11/16/18 CIN, compared with 148 cases in the placebo group, providing the vaccine efficacy of 96%.

"And for CIN [grade] 2 or worse, including adenocarcinoma in situ, there was 1 case in the vaccine group and 76 cases in the placebo arm, for a 99% efficacy rate," he said, adding that vaccine efficacy against HPV 6/11/16/18-related CIN ranged from 95.5% to 100% based on CIN grade. (Grade 1 is low-grade squamous intraepithelial lesion; grades 2 and 3 are high-grade squamous intraepithelial lesions.)

The single case of CIN 3 in the vaccinated group (there were 46 in the placebo arm) was a Brazilian woman who was positive for HPV 52 at day 1 and at 32 months was shown to be positive for both 52 and 16. She subsequently underwent a loop electrosurgical excision procedure.

"The lifetime risk of acquiring an HPV infection for sexually active people is 50%, and approaches 75% in some settings," Dr. Olsson explained, adding that HPV causes cervical cancer in 3%-4% of unscreened women. "When we do the screening, we reduce the frequency of cervical cancer, but in doing so we create a new disease … CIN."

A separate analysis of data from this same cohort of women suggests that in these women, aged 16-26 years, Gardasil vaccination reduces the overall incidence of Pap abnormalities regardless of the HPV types involved.

In a poster presentation, the researchers analyzed the impact on rates of abnormal Pap tests in women who, at day 1 of the study, had a negative Pap test and were DNA negative to 14 common HPV types and seronegative to the four vaccine HPV types discussed above.

In this generally HPV-naïve population, Gardasil prevented almost half of high-grade squamous intraepithelial lesions, compared with placebo. "Given these results, the impact on HPV 6/11/16/18-related Pap abnormalities is expected to be dramatic," the authors wrote.

CHICAGO — The quadrivalent human papillomavirus vaccine, which protects women against HPV types 6, 11, 16, and 18, also prevents the abnormal growth of precancerous cells in the cervix associated with these four types.

This finding, from the international phase IIb/III Quadrivalent HPV Vaccine Study, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

These premalignancies, known as cervical intraepithelial neoplasia (CIN), are a major contributor to health care costs resulting from screening, research, and treatment, Dr. Sven-Eric Olsson said at the conference, which was sponsored by the American Society for Microbiology.

Through 3 years of follow-up, the vaccine was 96% effective in preventing CIN related to HPV types 6, 11, 16, and 18, and vaccine efficacy was significant for all four of the HPV types, though somewhat less so for HPV 11, said Dr. Olsson, with the Karolinska Institute at Danderyds Hospital in Stockholm.

The Food and Drug Administration-approved quadrivalent HPV vaccine (Gardasil; Merck & Co.) is recommended by the Centers for Disease Control and Prevention for use by women aged 9-26 years. The four targeted HPV types are responsible for 70% of cervical cancers and 90% of genital warts, according to the CDC.

The investigators drew data from more than 18,000 women aged 16-26 years who were enrolled in one of three randomized trials sponsored by Merck.

The cohort of women was evenly divided to receive either vaccine or placebo at day 1, month 2, and month 6. Subjects underwent cervicovaginal sampling at day 1 and month 7 and Pap testing at day 1 and 6- to 12-month intervals for up to 48 months.

All of the specimens were HPV typed and histologically diagnosed by a four-member blinded pathology panel, said Dr. Olsson. He has given lectures for Merck but has no financial stake in either Merck or GlaxoSmithKline, which has filed with the FDA for approval of Cervarix, a bivalent HPV vaccine protecting against types 16 and 18.

Primary per protocol vaccine efficacy analysis included subjects who received all three of the doses, were sero- and PCR-negative to the four HPV types at day 1 and PCR-negative through month 7, and had no major protocol deviations.

Dr. Olsson reported that in the group that received the vaccine, there were 6 cases of HPV 6/11/16/18 CIN, compared with 148 cases in the placebo group, providing the vaccine efficacy of 96%.

"And for CIN [grade] 2 or worse, including adenocarcinoma in situ, there was 1 case in the vaccine group and 76 cases in the placebo arm, for a 99% efficacy rate," he said, adding that vaccine efficacy against HPV 6/11/16/18-related CIN ranged from 95.5% to 100% based on CIN grade. (Grade 1 is low-grade squamous intraepithelial lesion; grades 2 and 3 are high-grade squamous intraepithelial lesions.)

The single case of CIN 3 in the vaccinated group (there were 46 in the placebo arm) was a Brazilian woman who was positive for HPV 52 at day 1 and at 32 months was shown to be positive for both 52 and 16. She subsequently underwent a loop electrosurgical excision procedure.

"The lifetime risk of acquiring an HPV infection for sexually active people is 50%, and approaches 75% in some settings," Dr. Olsson explained, adding that HPV causes cervical cancer in 3%-4% of unscreened women. "When we do the screening, we reduce the frequency of cervical cancer, but in doing so we create a new disease … CIN."

A separate analysis of data from this same cohort of women suggests that in these women, aged 16-26 years, Gardasil vaccination reduces the overall incidence of Pap abnormalities regardless of the HPV types involved.

In a poster presentation, the researchers analyzed the impact on rates of abnormal Pap tests in women who, at day 1 of the study, had a negative Pap test and were DNA negative to 14 common HPV types and seronegative to the four vaccine HPV types discussed above.

In this generally HPV-naïve population, Gardasil prevented almost half of high-grade squamous intraepithelial lesions, compared with placebo. "Given these results, the impact on HPV 6/11/16/18-related Pap abnormalities is expected to be dramatic," the authors wrote.

CHICAGO — The quadrivalent human papillomavirus vaccine, which protects women against HPV types 6, 11, 16, and 18, also prevents the abnormal growth of precancerous cells in the cervix associated with these four types.

This finding, from the international phase IIb/III Quadrivalent HPV Vaccine Study, was reported at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

These premalignancies, known as cervical intraepithelial neoplasia (CIN), are a major contributor to health care costs resulting from screening, research, and treatment, Dr. Sven-Eric Olsson said at the conference, which was sponsored by the American Society for Microbiology.

Through 3 years of follow-up, the vaccine was 96% effective in preventing CIN related to HPV types 6, 11, 16, and 18, and vaccine efficacy was significant for all four of the HPV types, though somewhat less so for HPV 11, said Dr. Olsson, with the Karolinska Institute at Danderyds Hospital in Stockholm.

The Food and Drug Administration-approved quadrivalent HPV vaccine (Gardasil; Merck & Co.) is recommended by the Centers for Disease Control and Prevention for use by women aged 9-26 years. The four targeted HPV types are responsible for 70% of cervical cancers and 90% of genital warts, according to the CDC.

The investigators drew data from more than 18,000 women aged 16-26 years who were enrolled in one of three randomized trials sponsored by Merck.

The cohort of women was evenly divided to receive either vaccine or placebo at day 1, month 2, and month 6. Subjects underwent cervicovaginal sampling at day 1 and month 7 and Pap testing at day 1 and 6- to 12-month intervals for up to 48 months.

All of the specimens were HPV typed and histologically diagnosed by a four-member blinded pathology panel, said Dr. Olsson. He has given lectures for Merck but has no financial stake in either Merck or GlaxoSmithKline, which has filed with the FDA for approval of Cervarix, a bivalent HPV vaccine protecting against types 16 and 18.

Primary per protocol vaccine efficacy analysis included subjects who received all three of the doses, were sero- and PCR-negative to the four HPV types at day 1 and PCR-negative through month 7, and had no major protocol deviations.

Dr. Olsson reported that in the group that received the vaccine, there were 6 cases of HPV 6/11/16/18 CIN, compared with 148 cases in the placebo group, providing the vaccine efficacy of 96%.

"And for CIN [grade] 2 or worse, including adenocarcinoma in situ, there was 1 case in the vaccine group and 76 cases in the placebo arm, for a 99% efficacy rate," he said, adding that vaccine efficacy against HPV 6/11/16/18-related CIN ranged from 95.5% to 100% based on CIN grade. (Grade 1 is low-grade squamous intraepithelial lesion; grades 2 and 3 are high-grade squamous intraepithelial lesions.)

The single case of CIN 3 in the vaccinated group (there were 46 in the placebo arm) was a Brazilian woman who was positive for HPV 52 at day 1 and at 32 months was shown to be positive for both 52 and 16. She subsequently underwent a loop electrosurgical excision procedure.

"The lifetime risk of acquiring an HPV infection for sexually active people is 50%, and approaches 75% in some settings," Dr. Olsson explained, adding that HPV causes cervical cancer in 3%-4% of unscreened women. "When we do the screening, we reduce the frequency of cervical cancer, but in doing so we create a new disease … CIN."

A separate analysis of data from this same cohort of women suggests that in these women, aged 16-26 years, Gardasil vaccination reduces the overall incidence of Pap abnormalities regardless of the HPV types involved.

In a poster presentation, the researchers analyzed the impact on rates of abnormal Pap tests in women who, at day 1 of the study, had a negative Pap test and were DNA negative to 14 common HPV types and seronegative to the four vaccine HPV types discussed above.

In this generally HPV-naïve population, Gardasil prevented almost half of high-grade squamous intraepithelial lesions, compared with placebo. "Given these results, the impact on HPV 6/11/16/18-related Pap abnormalities is expected to be dramatic," the authors wrote.