Global access to HPV vaccination: what are we waiting for?

[Guest guest]

It's not enough that we have killed or injured so many in developed countries -

it's now time to extend Gardasil's reach

*********************************************************

The Lancet, Early Online Publication, 3 December 2009

Global access to HPV vaccination: what are we waiting for?

Original Text

M Clifford aEmail Address

Vaccines have repeatedly proven successful in the fight against infectious

diseases, bringing some equity in health care to even the least developed

regions of the world. Therefore the hope is that newly licensed human

papillomavirus (HPV) vaccines will have an effect on the estimated 0·5 million

cases of cervical cancer that arise worldwide every year, including the 80% that

occur in developing countries (figure).1, 2 From extrapolation of the impressive

efficacy against high-grade precancerous lesions in large phase 3 trials,3, 4

vaccination of girls before they reach adolescence against HPV types 16 and 18

(HPV 16/18) would be cost effective in the prevention of cervical cancer in even

the poorest countries, provided the cost of vaccination falls to US$10.5, 6

However, the greatest source of uncertainty with respect to the potential effect

of HPV vaccines remains the duration of the immune response. If vaccine boosters

are needed later, the complexity of programme delivery, particularly in

low-resource countries, increases considerably.

Click to toggle image size

Click to toggle image size

Figure Full-size image (62K)

Age-standardised mortality rate from cervical cancer per 100 000 women

In The Lancet today, the GlaxoKline Vaccine HPV-007 Study Group7 report an

extended follow-up (>6 years) of a phase 2 trial of the immunisation of young

women, who were not exposed to virus types 16 or 18 at baseline, with the HPV

16/18 vaccine. This period is the longest reported for any HPV vaccine so far.

No breakthrough cases of HPV 16/18 persistent infection or associated cervical

intraepithelial neoplasia grade 2 or worse (CIN2+) were reported in the

vaccinated women, which equates to a vaccine efficacy of 100% at 6 years.

Nevertheless, because the number of accrued events in the placebo group remains

small, this trial is not suitably powered to capture any small waning of

efficacy, should it occur, with time. In the large phase 3 PATRICIA (PApilloma

TRIal against Cancer In young Adults) trial,3 efficacy of the same bivalent

vaccine against HPV-16/18-associated CIN2+ was more robustly estimated at 98%,

consistent with data reported for the quadrivalent vaccine,4 and significant

(estimated at 53%) cross-protection against CIN2+ associated with HPV 31, 33,

45, 52, and 58.3

For the prediction of the long-term duration of immunity, perhaps the most

interesting data in today's report are those for immunogenicity. After an

initial drop from the peak antibody titres at month 7, there was no evidence of

further decline from 3 years to 6 years, which suggests that mean antibody

concentrations should remain well above those associated with natural infection

long into the future (and for ≥20 years according to the results of a

statistical model).8

Both HPV vaccines are prophylactic and have no effect on existing HPV

infection.9, 10 Noteworthy was that the women with evidence of HPV infection

were almost entirely absent from all analyses by the Study Group, which means

that the analysis of the total vaccinated cohort should not be interpreted as an

intention-to-treat analysis of all women aged 15—25 years, many of whom were

not HPV-16/18-naive.

The GAVI Alliance subsidises the provision of vaccines to the poorest countries,

and is currently reviewing HPV vaccine as a candidate for sustainable financing.

If, as hoped, some resources can be raised, eligible countries will need to

obtain the maximum health benefit for every dose of HPV vaccine that they

administer. Therefore priority needs to be given to preadolescent girls before

sexual activity. Immunisation of older boys or women (other than in a very

restricted catch-up programme), will always be a less effective use of resources

than will further improvement of coverage among preadolescent girls.11, 12 The

target age, thus, is a balance being early enough to catch girls before sexual

debut, but late enough to provide an as yet unknown duration of immunity that

protects during as many subsequent years of sexual activity as possible. The

data in today's study would suggest that this window of protection is at least 6

years, but also leads us to strongly suspect that, as these and other vaccinated

women are followed up, the period of protection might be much longer.

I declare that I have no conflicts of interest.

References

1 Parkin DM. The global health burden of infection-associated cancers in the

year 2002. Int J Cancer 2006; 118: 3030-3044. CrossRef | PubMed

2 Ferlay J, Bray F, Pisani P, Parkin DM. Globocan 2002: incidence, mortality and

prevalence worldwide [CD-ROM]. Lyon: International Agency for Research on

Cancer, 2004.

3 Paavonen J, Naud P, Salmerón J, et alfor the HPV PATRICIA Study Group.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against

cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final

analysis of a double-blind, randomised study in young women. Lancet 2009; 374:

301-314. Summary | Full Text | PDF(272KB) | CrossRef | PubMed

4 The FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus

to prevent high-grade cervical lesions. N Engl J Med 2007; 356: 1915-1927.

CrossRef | PubMed

5 Goldie SJ, O'Shea M, M, Kim SY. Benefits, cost requirements and

cost-effectiveness of the HPV16,18 vaccine for cervical cancer prevention in

developing countries: policy implications. Reprod Health Matters 2008; 16:

86-96. CrossRef | PubMed

6 M, Kim JJ, Albero G, et al. Health and economic impact of HPV 16 and 18

vaccination and cervical cancer screening in India. Br J Cancer 2008; 99:

230-238. CrossRef | PubMed

7 The GlaxoKline Vaccine HPV-007 Study Group. Sustained efficacy and

immunogenicity of the human papillomavirus (HPV)-16/18 AS04 adjuvanted vaccine:

analysis of a randomised placebo-controlled trial up to 6·4 years. Lancet

200910.1016/S0140-6736(09)61567-1. published online Dec 3. PubMed

8 MP, Van Herck K, Hardt K, et al. Long-term persistence of anti-HPV-16

and -18 antibodies induced by vaccination with the AS04-adjuvanted cervical

cancer vaccine: modeling of sustained antibody responses. Gynecol Oncol

200910.1016/j.ygyno.2009.01.011. published online Feb 12. PubMed

9 Hildesheim A, Herrero R, Wacholder S, et alfor the Costa Rican HPV Vaccine

Trial Group. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine

among young women with preexisting infection: a randomized trial. JAMA 2007;

298: 743-753. CrossRef | PubMed

10 The FUTURE II Study Group. Prophylactic efficacy of a quadrivalent human

papillomavirus (HPV) vaccine in women with virological evidence of HPV

infection. J Infect Dis 2007; 196: 1438-1446. CrossRef | PubMed

11 Kim JJ, Andres-Beck B, Goldie SJ. The value of including boys in an HPV

vaccination programme: a cost-effectiveness analysis in a low-resource setting.

Br J Cancer 2007; 97: 1322-1328. CrossRef | PubMed

12 Jit M, Choi YH, Edmunds WJ. Economic evaluation of human papillomavirus

vaccination in the United Kingdom. BMJ 2008; 337: a769. PubMed

a International Agency for Research on Cancer, 69372 Lyon cedex 08, France