To the Editor: It’s all very difficult isn’t it? Teasing out the issues around impartiality, weighing evidence and competing interests? Wain wrote a recent editorial for the Journal, and included a list of his “competing interests”:

• Chair of the CSL Gardasil Advisory Board;

• speaker fees, travel assistance and consultancy fees from CSL Biotherapies and from Merck and its affiliates in relation to Gardasil; and

• shares in CSL Limited.1

He helpfully advises that Gardasil (Merck) “is available at no cost to Australian girls and women between the ages of 12 and 26 as part of the National Immunisation Program. The bivalent vaccine, Cervarix (GlaxoSmithKline), has to date not been included in the program, having initially been rejected by the Pharmaceutical Benefits Advisory Committee (PBAC) on the basis of uncertain cost-effectiveness, but subsequently recommended for inclusion.”1

This is disingenuous at best. Initially, the PBAC also “rejected the application for [Gardasil] . . . based on unacceptable and uncertain cost-effectiveness at the price requested.”2 At the request of the then Health Minister, the PBAC reviewed its decision after the company made some small changes to its submission, including a change in pricing.

At about the time Wain’s editorial was published, a hard copy of the previous Medical Journal of Australia article on human papillomavirus (HPV) arrived on my desk,3 courtesy of GlaxoSmithKline. That article on HPV vaccination listed the “competing interests” at the end. Clearly, all the authors have received some sort of funding through GlaxoSmithKline, CSL and/or Merck.

I am not impressed by authors who receive funding from pharmaceutical companies that market the drugs they are discussing. It seems to me that the problem lies with interests not competing, or at least not competing with the author’s intent. Perhaps a little healthy competition would bring out some more thoughtful, articulate articles, unaffected by any commercial pressures.

“A plague o’ both your houses.” Let’s consider where we could best spend our money without the help of the competing interests of various pharmaceutical marketing mechanisms. “HPV vaccination will not prevent all cases of cervical cancer, therefore vaccinated women should continue to have two yearly Pap smears.”4 Given that HPV vaccination (in this country) will not change the rate of cervical screening required in the near future, perhaps the money would be better spent on ensuring that all Australian women are screened in a timely manner. That is, ensuring that poor women, Indigenous women, rural women, and immigrant women are part of “Cervical screening in Australia . . . one of the great public health success stories, as witnessed by a continuing dramatic fall in the incidence of carcinoma of the cervix and mortality from this disease since the introduction of the National Cervical Screening Program (NCSP).”5

To the Editor: We would like to express our disappointment with the Journal’s decision to publish an editorial on human papillomavirus (HPV) vaccines that demonstrated significant bias.1 It seems that simply documenting an author’s conflicts of interest exonerates the author and relieves the Journal of the responsibility of considering whether or not the article is biased.

In his article, Wain states that the bivalent vaccine, Cervarix (GlaxoSmithKline), has not been included in the National Immunisation Program, having initially been rejected by the Pharmaceutical Benefits Advisory Committee (PBAC) on the grounds of uncertain cost-effectiveness. He omits to mention that Gardasil (Merck), was initially also rejected, and only funded after political intervention, an emergency meeting of the PBAC and further price negotiations with CSL.2

Wain claims that Cervarix is being promoted to older women despite the absence of efficacy data and the uncertain population benefits in this age group. Surely a balanced argument would include the fact that Gardasil is licensed for boys aged from 9–15 years based on immunogenicity data only, and that efficacy has not been established in this population. Why does the author consider this to be acceptable, but that licensing the vaccine for older women where the indication is to prevent cervical cancer is unacceptable? Many vaccines are licensed on the basis of immunogenicity data provided these have been shown to predict efficacy. While the efficacy of HPV vaccines in older women is being established, there are good data to show that an immune response to HPV vaccine is predictive of efficacy.3 Women aged over 26 years produce a robust immune response to HPV vaccines, similar to levels achieved in women aged 15–25 years, for whom efficacy has already been demonstrated. The Therapeutic Goods Administration has licensed Cervarix for women aged 26–45 years, before efficacy data became available, based on the assumption that efficacy will be demonstrated in seronegative older women.

Women of all ages have shown interest in benefiting from a vaccine to protect against cervical cancer.4 Women of any age have the right to be informed, and to have the opportunity to discuss with their treating physician the relative benefits and risks of receiving the HPV vaccine for prevention of cervical cancer.

Many vaccines are initially available only if purchased by individuals and, although this may result in inequity, ultimately, this is a decision of priority (individual financial and public health funding priorities) and not a reason to withhold licensing a vaccine with proven benefit.

To the Editor: Wain’s criticism of the Australian Therapeutic Goods Administration (TGA) approval of the bivalent vaccine, Cervarix (GlaxoSmithKline), suggesting it did not adhere to World Health Organization guidelines,1 should not detract from the potential benefits of human papillomavirus (HPV) vaccination in women over 26 years of age.

An immunogenicity study showed all women up to the age of 55 years seroconverted to both HPV types and, while mean antibody concentrations at Month 7 were lower than in the younger age group, they were still three to four times higher than those observed in 15–25-year-old women in the long-term follow-up study (up to 4.5 years after vaccination), where continued efficacy was demonstrated.2 HPV infection is most prevalent in younger age groups, with one study showing a prevalence of 44.8% in women aged 20–24 years.3 As indicated by Wain, the vaccine has diminished efficacy in populations with high rates of previous exposure. Thus, 20–24-year-olds would benefit least, and if we extrapolate his argument, should not be included in any catch-up vaccination program. The United Kingdom has, in fact, recommended a catch-up campaign for girls aged up to 18 years only. The prevalence of HPV infection decreases after 26 years of age, and these “older” women should benefit from vaccination as supported by preliminary efficacy data of the quadrivalent vaccine Gardasil (Merck) in an older population.4 This vaccine may also be protective for women who have been previously exposed to the same subtypes of HPV as the vaccines, as shown by 100% efficacy against cervical intraepithelial neoplasia (CIN) grade 2/3 or adenocarcinoma in situ (AIS) among people who are seropositive but HPV-DNA-negative to the relevant HPV type.5

The Pharmaceutical Benefits Advisory Committee initially did not recommend funding for Gardasil on the basis of cost-effectiveness until after an extraordinary meeting to consider a revised submission, following an “unusual” request from the Health Minister.6,7 CSL agreed to reduce the price, undertook to make a substantial contribution to any booster program if it became necessary in the next 20 years, and also to the costs of setting up a national register to link vaccination data to later cervical screening records.

It is obvious that the efficacy of HPV vaccines will inevitably be lower after commencement of sexual activity, but we believe that it is the medical practitioner’s responsibility to offer women aged over 26 years the current, albeit incomplete, information on vaccine efficacy, and allow women to make the choice.