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U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.
Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.
National Cancer Institute
U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18. Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.
The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.
HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).
HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.
Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.
The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.
American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.
A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.
Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.
Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).
"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.
Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."
He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.
Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.
ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.
Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.
ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.