A single dose of a vaccine against human papillomavirus (HPV) may prevent cervical cancer as effectively as the standard three-dose regimen, researchers concluded after analyzing the combined results of two large vaccine trials. The HPV vaccine in these studies was Cervarix (GlaxoSmithKline), which is effective against HPV strains 16/18.
If randomized controlled trials ultimately support the result of this post hoc analysis, it could broaden protection against cervical cancer in areas of the world where vaccination programs are hardest to administer and where cervical cancer is disproportionately burdensome, the study authors say.
“Even if you ignore the expense, the feasibility of implementing and getting back to individuals for a second and third dose is quite challenging, especially in places where there is no infrastructure,” coauthor Cosette Wheeler, PhD, Regents Professor, Pathology and Obstetrics and Gynecology, University of New Mexico Health Sciences Center in Albuquerque, told Medscape Medical News.
The studies are published online June 10 in the Lancet Oncology.
The possibility of a single-dose HPV vaccine is “a huge public health win,” coauthor Aimée R. Kreimer, PhD, Investigator, Division of Cancer Epidemiology & Genetics, National Cancer Institute, Bethesda, Maryland, told Medscape Medical News. “Even if one dose protects only against HPV types included in the vaccine formulation, if we vaccinated most girls, we would have the chance to reduce cervical cancer by around 75%.”
That’s the exciting part, Dr Wheeler added. “If we’re able to achieve success with one dose, or frankly even with two doses, that makes the possibility for worldwide prevention much greater.”
HPV type 16 is the leading cause of cervical cancer, responsible for about 50% of all cases, and HPV 18 is the second-largest cause, at 20%.The authors note that this research was carried out with Cervarix, and it is unclear whether the results would also apply to the other HPV vaccine that is available, Gardasil (Merck & Co.), which is active against several more HPV strains and is the product that is commonly used in the United States. Whether results of this trial have any bearing on Gardasil will depend on what’s driving the strong immune response to Cervarix, the authors suggest. Cervarix carries a proprietary adjuvant, which may be responsible for the immune response.
Surprise Over Efficacy Findings
The idea of the current post hoc analysis arose from results in the large randomized controlled Costa Rica Vaccine Trial, in which about 20% of participants received fewer than three doses of HPV-16/18 vaccine. “We were surprised to observe that efficacy was the same regardless of the number of doses received,” Dr Kreimer told Medscape Medical News.
That led to the post hoc analysis of the immunization results from the Costa Rica Vaccine Trial combined with results from the only other large phase 3, double-blind, randomized trial of HPV-16/18, for a total of more than 14,000 participants, ages 15 to 25 years, including about 7000 control subjects. The second trial, called PATRICIA (Papilloma Trial Against Cancer in Young Adults), took place in 14 countries. The analysis found that 4 years after vaccination, women who received the required three vaccine doses and women who received fewer than three doses — usually due to pregnancy or a colposcopy referral — were equally protected against HPV-16/18. Further, the analysis showed a potential benefit of cross-protection against closely related HPV strains 31/35/45 among women whose two doses were 6 months apart — a benefit previously seen only with three doses.
Four-year vaccine efficacy against HPV-16/18 in the combined analysis was 77% for the 13,296 (6634 case, 6662 control) women in the three-dose group, 76% for the 549 (273 case, 276 control) women in the two-dose group, and 85.7% for the 238 (138 case, 100 control) women in the single-dose group. Efficacy against the closely related HPV-31/33/35 was 59.7% for three doses, 37.7% for two doses, and 36.6% for one dose. When data for the two doses were analyzed according to dosing regimen, the cross-protective efficacy was 10.1% for those who received their second dose 1 month after the first and 68.1% for those who received the second dose at 6 months.
Antibody concentrations for two doses given 6 months apart were very close to concentrations for three doses, the research showed. One-dose vaccination titers at 6 to 48 months were lower than those for two or three doses, “but the titers were stable and several times higher than those identified for natural immunity,” the researchers write. “We can now infer that these lower, vaccine-induced antibody titers provide as strong HPV prevention as the titers from two or three doses, at least in the short term.”
Just how long these vaccines will provide protection still needs to be determined. “We know with three doses we can see the protection going out toward 10 years, and we hope that maybe the protection is lifelong,” commented Dr Wheeler. “That does not mean that we know we will never need a booster. And that doesn’t mean if we give less than three doses that we know about the longevity or durability of that protection. So that’s another piece of the puzzle.”
Although these results cannot be applied to Gardasil, Dr Wheeler notes that studies looking at Gardisil antibody titers after two doses look promising.
In an accompanying comment, Julia M.L. Brotherton, Medical Director, National HPV Vaccination Program Register, VCS Registries, East Melbourne, Victoria, Australia, commented: “These data suggest that one dose of bivalent HPV vaccine might be adequate to protect against HPV-16 and HPV-18 persistent infections and, therefore, probably disease. HPV-16 and HPV-18 cause more than 70% of cervical cancers and the vast majority of HPV-related cancers at other anatomic sites. If this finding is confirmed, it opens up a great opportunity to extend the reach of protection using HPV vaccines to more people than we would have previously thought possible.”
Four authors of the study are GSK employees and own shares and stock options in the company. Other researchers had financial or advisory relationships GSK, Roche Molecular Systems, Merck, and Sanofi Pasteur MSD. Dr Brotherton notes that she has been an investigator for investigator-initiated HPV epidemiology research grants partially funded by bioCSL/Merck, but this did not involve financial compensation.
*This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.
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