In the Journals

9-valent HPV vaccine noninferior to quadrivalent HPV vaccine

A 9-valent HPV vaccine safely and effectively prevented infection and disease related to five types of HPV not targeted by the quadrivalent vaccine, according to study results.

The 9-valent (Gardasil 9, Merck) and quadrivalent (Gardasil, Merck) vaccines also demonstrated comparable antibody responses to the four HPV types the quadrivalent vaccine is designed to prevent, results showed.

Elmar A. Joura, MD, of the department of gynecology and obstetrics at Medical University of Vienna in Austria, and colleagues sought to evaluate the efficacy of the investigational 9-valent viruslike particle vaccine against HPV. The 9-valent HPV vaccine includes the four HPV types in the quadrivalent vaccine — 6, 11, 16 and 18 — as well as five additional oncogenic types: 31, 33, 45, 52 and 58.

The analysis included 14,215 women aged 16 to 26 years (median age, 22 years). Researchers assigned patients a series of three injections of the 9-valent HPV vaccine (n = 7,106) or the quadrivalent HPV vaccine (n = 7,109). The second injection was administered at month 2 and the third injection was administered at month 6.

Overall, 14 cases of high-grade cervical, vulvar and vaginal disease per 1,000 person-years occurred in each vaccine group.

When researchers excluded data from participants with HPV infection at baseline, the incidence of high-grade cervical, vulvar and vaginal disease was 2.4 cases per 1,000 person-years in the 9-valent vaccine group and 4.2 cases per 1,000 person-years in the quadrivalent vaccine group. This equated to a 42.5% (95% CI, 7.9-65.9) risk reduction in the 9-valent HPV cohort.

Among participants without HPV infection at baseline, the 9-valent HPV vaccine was associated with 100% (95% CI, 70.4-100) efficacy against the nine vaccine HPV types, and 19.7% (95% CI, –34.5 to 52.5) efficacy for other HPV types not included in the vaccine.

High-grade disease related to HPV types 31, 33, 45, 52 or 58 occurred in one participant in the 9-valent vaccine group compared with 30 in the quadrivalent vaccine group (risk reduction, 96.7%; 95% CI, 80.9-99.8).

Researchers also found the 9-valent HPV vaccine was noninferior to the quadrivalent HPV vaccine for HPV types 6, 11, 16 and 18. The geometric mean titer for noninferiority was 0.8 for HPV-11 (95% CI. 0.77-0.83); 1.02 for HPV-6 (95% CI, 0.99-1.06); 0.99 for HPV-16 (95% CI, 0.96-1.03); and 1.19 for HPV-18 (95% CI, 1.14-1.23).

Injection site-related adverse events occurred more frequently in participants in the 9-valent cohort (90.7% vs. 84.9%). Systemic events — the most common of which were headache, pyrexia, nausea, dizziness and fatigue — occurred in a comparable proportion of participants in each arm (55.8% vs. 54.9%).

“The results of this study showed that the prophylactic administration of 9-valent HPV vaccine prevented infection and disease associated with the vaccine HPV types,” Joura and colleagues wrote. “The effect of vaccination on the burden of cancer remains to be determined.”

Given the efficacy of HPV vaccination, efforts need to be made to improve vaccination rates in adolescents, Anne Schuchat, MD, director of CDC’s National Center for Immunization and Respiratory Diseases, wrote in an accompanying editorial.

“Even with the availability of another HPV vaccine targeting additional cancer-causing virus types, vaccination of a much high proportion of preteens is needed,” Schuchat wrote. “Otherwise, decades from now oncologists will still be talking about HPV-associated cancers with thousands of new patients every year. Instead, I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered.” – by Alexandra Todak

Disclosure: The study was funded by Merck. Joura reports lecture/advisory board fees and grant support from GlaxoSmithKline, Merck, Roche and Sanofi Pasteur MSD. See the full study for a list of all other researchers’ relevant financial disclosures.

A 9-valent HPV vaccine safely and effectively prevented infection and disease related to five types of HPV not targeted by the quadrivalent vaccine, according to study results.

The 9-valent (Gardasil 9, Merck) and quadrivalent (Gardasil, Merck) vaccines also demonstrated comparable antibody responses to the four HPV types the quadrivalent vaccine is designed to prevent, results showed.

Elmar A. Joura, MD, of the department of gynecology and obstetrics at Medical University of Vienna in Austria, and colleagues sought to evaluate the efficacy of the investigational 9-valent viruslike particle vaccine against HPV. The 9-valent HPV vaccine includes the four HPV types in the quadrivalent vaccine — 6, 11, 16 and 18 — as well as five additional oncogenic types: 31, 33, 45, 52 and 58.

The analysis included 14,215 women aged 16 to 26 years (median age, 22 years). Researchers assigned patients a series of three injections of the 9-valent HPV vaccine (n = 7,106) or the quadrivalent HPV vaccine (n = 7,109). The second injection was administered at month 2 and the third injection was administered at month 6.

Overall, 14 cases of high-grade cervical, vulvar and vaginal disease per 1,000 person-years occurred in each vaccine group.

When researchers excluded data from participants with HPV infection at baseline, the incidence of high-grade cervical, vulvar and vaginal disease was 2.4 cases per 1,000 person-years in the 9-valent vaccine group and 4.2 cases per 1,000 person-years in the quadrivalent vaccine group. This equated to a 42.5% (95% CI, 7.9-65.9) risk reduction in the 9-valent HPV cohort.

Among participants without HPV infection at baseline, the 9-valent HPV vaccine was associated with 100% (95% CI, 70.4-100) efficacy against the nine vaccine HPV types, and 19.7% (95% CI, –34.5 to 52.5) efficacy for other HPV types not included in the vaccine.

High-grade disease related to HPV types 31, 33, 45, 52 or 58 occurred in one participant in the 9-valent vaccine group compared with 30 in the quadrivalent vaccine group (risk reduction, 96.7%; 95% CI, 80.9-99.8).

Researchers also found the 9-valent HPV vaccine was noninferior to the quadrivalent HPV vaccine for HPV types 6, 11, 16 and 18. The geometric mean titer for noninferiority was 0.8 for HPV-11 (95% CI. 0.77-0.83); 1.02 for HPV-6 (95% CI, 0.99-1.06); 0.99 for HPV-16 (95% CI, 0.96-1.03); and 1.19 for HPV-18 (95% CI, 1.14-1.23).

Injection site-related adverse events occurred more frequently in participants in the 9-valent cohort (90.7% vs. 84.9%). Systemic events — the most common of which were headache, pyrexia, nausea, dizziness and fatigue — occurred in a comparable proportion of participants in each arm (55.8% vs. 54.9%).

“The results of this study showed that the prophylactic administration of 9-valent HPV vaccine prevented infection and disease associated with the vaccine HPV types,” Joura and colleagues wrote. “The effect of vaccination on the burden of cancer remains to be determined.”

Given the efficacy of HPV vaccination, efforts need to be made to improve vaccination rates in adolescents, Anne Schuchat, MD, director of CDC’s National Center for Immunization and Respiratory Diseases, wrote in an accompanying editorial.

“Even with the availability of another HPV vaccine targeting additional cancer-causing virus types, vaccination of a much high proportion of preteens is needed,” Schuchat wrote. “Otherwise, decades from now oncologists will still be talking about HPV-associated cancers with thousands of new patients every year. Instead, I hope that in a few decades we will be able to tell a generation of adults who never had HPV-associated cancers or precancers that when they were teenagers, we had them covered.” – by Alexandra Todak

Disclosure: The study was funded by Merck. Joura reports lecture/advisory board fees and grant support from GlaxoSmithKline, Merck, Roche and Sanofi Pasteur MSD. See the full study for a list of all other researchers’ relevant financial disclosures.