Thursday, October 6, 2011

Now the History of Vaccines Blog, too

I can't believe they did it, too:
A study published in the October 3, 2011, issue of the Journal of Clinical Oncology reveals a startling rise in the rate of throat cancers related to human papillomavirus (HPV). The study looked at specimens from 271 throat cancers (specifically oropharyngeal squamous cell carcinomas, or OPSCC) collected over 20 years. The researchers found that HPV prevalence in the cancers increased from 16.3% during 1984 to 1989 to 71.7% during 2000 to 2004. They note that "The overall rise in OPSCC incidence during 1984 to 2004 is largely explained by the increasing incidence of HPV-positive cancers, whereas incidence of HPV-negative cancers declined.”
As I pointed out yesterday, these percentages are absolutely meaningless in detecting an increase in HPV-associated OP cancers or OP cancers in general. The only figures of significance in this determination are incidence rates. From the article's abstract:
Population-level incidence of HPV-positive oropharyngeal cancers increased by 225% (95% CI, 208% to 242%) from 1988 to 2004 (from 0.8 per 100,000 to 2.6 per 100,000), and incidence for HPV-negative cancers declined by 50% (95% CI, 47% to 53%; from 2.0 per 100,000 to 1.0 per 100,000). If recent incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020.
Ignore the percentages here, too, as they're useless and misleading. In terms of the actual (estimated) incidence, we're talking about an increased incidence of HPV-positive OP cancers from 0.8 to 2.6 per 100,000 and a decreased incidence of HPV-negative OP cancers from 2.0 to 1.0 per 100,000 in the US over the period 1988-2004. This resulted in an overall increase of 0.8 per 100,000 - from 2.8 per 100,000 to 3.6 per 100,000. This results from a +1.8 change in HPV-positive OP cases and a -1.0 change in HPV-negative OP cases. I questioned in my previous post about this whether an increase of 1.8 cases per 100,000 of a disease over a 16-year period constitutes a "dramatic" rise in HPV-associated OP cancer, and I would ask the same about the overall increase. I find it difficult to imagine that an increase of less than one case per 100,000 over 16 years, even for a rare disease, is a "startling" increase.

The changing HPV-positive and -negative proportions of OP cases (from 16% to 72% HPV-positive) can in some sense be seen as 'good' news. First, the fact that it partially results from a decline in smoking-associated cases reflects a decline in smoking, and smoking causes a gamut of other health problems. Second, as the abstract notes,
Median survival was significantly longer for HPV-positive than for HPV-negative patients (131 v 20 months; log-rank P < .001; adjusted hazard ratio, 0.31; 95% CI, 0.21 to 0.46). Survival significantly increased across calendar periods for HPV-positive (P = .003) but not for HPV-negative patients (P = .18).
So HPV-positive OP cancers are much more survivable than HPV-negative OP cancers, and treatments for the former have improved while those for the latter have continued to be less successful. The bad news is that the number of cases of HPV-positive OP is expected to grow as the virus (especially HPV 16) spreads further through the population.

And of course there are HPV vaccines that could help to prevent against infection with the strain (HPV 16) responsible for almost all HPV-positive OP cancers. The HoV Blog reports:
We spoke with Paul A. Offit, MD, chief of Infectious Diseases at The Children’s Hospital of Philadelphia, about the new study and its implications for HPV vaccination for boys. When asked whether we have evidence that HPV vaccination prevents throat cancers in males, Offit said, “What we do have is evidence that HPV vaccination can prevent infection. And since we know that a cell cannot become cancerous [with HPV-related cancer] unless it was infected with HPV, then the vaccine will protect against oropharyngeal cancers in men.”

Moreoever, Offit noted that we do not have direct evidence that HPV vaccination prevents cervical cancer in girls; what we have is compelling evidence that the vaccine prevents the cervical intraepithelial neoplasias that are requisites for cervical cancers. “So, for boys, we have the same thing: a cell can’t be transformed unless it is infected with HPV. And we have data that the vaccine prevents infections.”
I have a couple of questions about this: Can "infections" be talked about in this general way? Can we assume that the vaccine would prevent oral HPV infection exactly the same as genital HPV infection? Are these entirely the same? I read one report that suggested that Maura Gillison (one of this study's authors, incidentally) successfully pilot-tested an indicator for HPV throat infection, so it seems like this could be used in determining efficacy in preventing infection... In any case, as I've said, it's a highly plausible assumption. The post continues:
Offit thinks that the recommendation HPV vaccination for boys will come soon, possibly at the end of this month when the Advisory Committee for Immunization Practices meets. The topic is on the committee’s agenda for Tuesday, October 25.
If the most optimistic hopes for the long-term efficacy and safety of the vaccine are realized, and if combined with other preventive measures, it will be a valuable addition (given to girls and boys pre-exposure) to the preventive arsenal against a number of diseases, including OP cancer. I trust the CDC will make its decisions based upon all of the existing knowledge (including knowledge of the uncertainties involved) and not meaningless percentages or media hype.

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