Are Gardasil Benefits Worth the Potential Side Effects?

The Gardasil results so far are in: a 17 to 45 percent reduction in abnormal Pap smears.

Merck’s newest press releases publicizes a study that showed a 96% protection against HPV strain type 16, (which causes some 53.2% of invasive cervical cancers) over 8.5 years—and sure, that’s impressive. But the drug company’s marketing department probably hoped that journalists wouldn’t read the rest of the press release too closely, particularly on a Friday. Or, come to that, ask about type 18, which causes 13.1% of cervical cancers and goes curiously unmentioned.

But about those reductions in abnormal Pap smears.

Two randomized, placebo-controlled trials of Gardasil followed 17,622 women who underwent Pap testing at the start of the trials and then every 6 to 12 months. All the women showed no exposure to 14 common HPV types and had normal Pap smears to begin with.

After 3.6 years, the results were as follows:

· 17 to 22 percent reduction in ASC-US: atypical squamous cells of undetermined significance associated with a high-risk type of HPV

· 17 percent reduction in LSIL: low-grade squamous intraepithelial lesion

· 36 percent reduction in ASC-H: atypical squamous cells/cannot exclude high-grade squamous intraepithelial lesion

· 45 percent reduction in HSIL: high-grade squamous intraepithelial lesion

Colposcopies were reduced by 20 percent, cervical biopsies by 22 percent and surgery and other invasive treatments by 42 percent.

Now, if you’re one of the women who’s suffered an abnormal Pap smear and/or cervical cancer, those results probably look pretty good to you.

But—seriously? That’s it? 17 to 45 percent reduction?

And I’m curious. Given that type 16 supposedly causes the vast majority of 66-70 percent of cervical cancer (18 trails it by a mile) but was shown in a study published in the Journal of the National Cancer Institute to be losing ground to non-18 types, did anyone check the results for evidence that other strains of HPV are becoming more common? Does anyone care?

Heck, I was starting to waver again on the news that cases of genital warts have dropped dramatically, according to recent reports from Australia. And I’m constantly looking at the Gardasil issue. I always keep in mind the possibility that at some point the pros might outweigh the cons (cons like the potential for some particularly nasty, if unproven, side effects as well as the unknown of replacement diseases like those that popped up with Prevnar.)

But if that’s all the protection we’re looking at just in the short-term, when women have been less exposed to HPV of all kinds than they probably will be later in life, not vaccinating seems like a no-brainer.

Cervarix versus Gardasil

The battle’s on. And let the marketing campaigns and medical sniping begin.

GlaxoSmithKline said today that the results of a comparative HPV vaccine study it had sponsored showed that Cervarix generated between two and six times as many antibodies as Gardasil.

Both vaccines utilize novel “virus-like particles,” VLPs. These are created by inserting DNA into yeast cells to make a genetically-engineered ‘seed stock’. The resulting paste is cultured in a fermenter to increase cell mass and then incubated; eventually the antigen VLPs are filtered from the paste and blended with adjuvants. The paste is then cleaned and reused.

Both vaccines protect against HPV strains 16 and 18, thought to be responsible for 66 to 70 percent of cervical cancers, although one study recently showed 16 to have been losing ground to strains other than 18 (there are believed to be up to 120 strains of HPV) for some years. Gardasil also protects against two wart-causing strains.

But Cervarix also uses a novel adjuvant containing aluminium salt and monophosphoryl lipid A (MPL), and according to GSK that makes a big difference in antibody levels—a claim that made a Merck spokesman sniff disparagingly, “It's disease efficacy that's really the most important, and we certainly have very high efficacy against some very important disease endpoints."

Cervarix has been used in the EU for some time and was chosen over Gardasil by Britain for its country-wide vaccination program. However, the FDA is currently looking it over for approval in the US, where Merck has had the market to itself up until now.

Both vaccines have been associated with side-effects including paralysis, convulsions and immune disorders, although no causal link has been proven and the CDC beleives that HPV vaccines are safe.

Approval for Cervarix in the US could come by the fall—so if you think the Gardasil campaign up to now has been aggressive, honey, you ain’t seen nothin’ yet.