Old and New Epidemics

H/T Jredheadgirl for noting reports of a new study showing human papilloma virus (HPV) present in cases of oropharyngeal squamous cell carcinoma (OPSCC) over the past 25 years.

October 5, 2011 — The sharp rise in oropharyngeal cancer associated with human papillomavirus (HPV) and its association with oral sex have been highlighted again, and this time has gained widespread media attention.

This new epidemic of HPV-positive oropharyngeal cancer has been brewing for a while now, as previously reported by Medscape Medical News…

The researchers, headed by Maura Gillison MD, PhD, professor of medicine and Jeg Coughlin Chair of Cancer Research at The Ohio State University Comprehensive Cancer Center in Columbus, report that there has been a dramatic increase in the incidence of oropharyngeal cancer since 1984.

A growing majority of new cases (70%) are associated with HPV, and the vast majority of patients are male.

My interest in HPV has risen over the past couple of years since learning that HPV-16 has been found present not only in cases of cervical cancer (which now has a vaccination jab available), but also in cases of genital and anal cancer, and even in mouth and throat and lung cancer. It’s had me wondering whether the cancer epidemic of the past century may have actually been caused by a virus, rather than by smoking or drinking.

But the new study (which is freely available online), which is based on tissue samples held since 1984, suggests that this is a new form of cancer, with only about 16% of the earliest samples testing positive for HPV as against 71% of the later samples testing positive. Which kind of suggests that HPV wasn’t very prevalent 25 years ago, but is far more prevalent now, and is therefore a mounting new epidemic:

If the current trends continue, HPV-related oropharyngeal cancer will become the major form of head and neck cancer by 2020, and will become the leading HPV-associated cancer in the United States, surpassing cervical cancer, Dr. Gillison said in a statement.

Well, on the face of it, it would certainly look like that. But, on closer inspection, a number of questions arise.

For a start, there are surprisingly few samples in this study, as the accompanying editorial points out.

During the two decades examined, there were approximately 200,000 patients with OPSCC nationwide. … this reconstruction of the history of OPSCC in the United States is based on only 271 patients.

Which works out at about 13 patients for each of the 20 or so years the study covered. That seems to be rather too few to get a definitive fix on whether this is a growing epidemic or not.

Furthermore, they say in the study that it’s a bit difficult to test old samples for HPV.

Because DNA and RNA from formalin-fixed, paraffin-embedded tumor specimens are known to degrade over time, laboratory assays were designed to account for this. Specimens were classified as evaluable or unevaluable for DNA amplification by polymerase chain reaction (PCR) by using a real-time TaqMan assay (Applied Biosystems) that amplified a 58 base-pair (bp) region of a control gene, human endogenous retrovirus-3 (ERV-3)…

We anticipated loss in assay sensitivity because of the age of specimens beyond the exclusion of unevaluable samples. Therefore, HPV prevalence in 69 cervical cancers was used to estimate sensitivity of each laboratory assay across calendar periods, assuming all cervical cancers were HPV-positive.

As I understand this, they tested the samples for common-or-garden ERV-3, and if they could produce a result for them, they included them in the study. And then they adjusted the results they got using similar results from cervical cancer samples which were assumed to all be HPV positive.

But ultimately, what this really means is that they couldn’t actually measure how much HPV-16 there was in the oldest samples, but they had to make an intelligent guess based on how much HPV-16 they found in similar aged cervical cancer samples. So if, say, only 75% of 20 year old, 100% HPV positive cervical samples actually tested positive, you’d get a sampling fraction of 75/100 or 0.75, and if 22% of your 20 year old oropharyngeal samples tested positive, you’d multiply this by a weighting 1/0.75 or 1.33 to give a ‘corrected’ value of 29%. And assuming that the cervical samples (all assumed to have tested positive for HPV) had similarly degraded with age, then you’d find that the weighting would increase with age, rising from 1.0 to higher values with increasing age.

Given that, it’s a bit strange to find that only 0.4% of the oldest oropharyngeal samples tested positive in the results they obtained. Yet the ‘corrected’ values (see right) appear in some cases to be exactly the same as the observed values (e.g. 1984). i.e. the weighting is 1.0.

I may be misreading this graph, of course. It says ‘Positive %’ on the y-axis, but it probably actually means ‘positive fraction‘, and 0.4 isn’t 0.4% but is actually 40%. But why such small corrections? And why are the youngest sample values corrected upwards more than the oldest? A closer examination of the paper revealed the explanation.

…we estimated sampling fractions for inclusion into our study (specific to age group, sex, race, registry, and calendar year [2-year groups]). The inverse of these sampling probabilities were used as weights to reweight the observed HPV prevalence in tested OPSCCs to all patients within Hawaii, Iowa, and LA (1988 to 2004; periods preceding 1988 were excluded because of sparse data).

So it would appear that the 1984 figure was not reweighted, because of sparse data. And that is why the ‘corrected’ value is the same as the observed value.

So what might the graph have looked like if a correctly reweighted value was used? The weighting is hardly likely to be 1.0. So it would seem reasonable to use some value similar to the other 3 weightings. I estimate these weightings to have been 2.34 for 1990, 1.23 for 1995, and 1.33 for 2000. If it’s assumed that the 1984 weighting would not be smaller than the 1990 weighting, then the reweighted 1984 result would be about 0.38 or 38% at minimum (1). But if the mean increase in weighting between periods (1.11 – 0.1)/2, or 0.5, was also added, then the 1985 weighting would be 2.84, and the reweighted percentage would be 43% (2). And if the overall trend of reweightings (the rate of change of reweighting) was estimated, the reweighted percentage might be as high as 54% (3). And the replotted graph would look like the graph at right.

And instead of the graph showing a growing HPV epidemic with 15% incidence in 1984 rising to a 75% incidence in 2004, it would show a much higher incidence – in the range 38% to 54% – in 1984. Which would suggest that HPV infection was already endemic in 1984.

And this dramatically different conclusion would be the result of simply reweighting a single unweighted number.

However, I’ve only looked at one of the graphs. Of the other three, two of them seem to have had their 1984 figures already mysteriously reweighted to produce values of 40-50%. Nevertheless the authors report a rise in the incidence of HPV-positive oropharyngeal cancer from 16% to 71% over 20 years.

And they may well be right, and this is an entirely new cancer epidemic to complement the prior booze-and-cigs-driven epidemic, which must necessarily be now fading out as fewer and fewer people smoke.  This is disease as relay race, and as one epidemic fades out, it passes the baton onto another epidemic! It lends further credence to this earlier, well-established dogma doctrine, but finds a new and rapidly growing epidemic – research into which will need funding, needless to say. And indeed they don’t say any such thing.

But on the other hand, with a slight correction of one of the figures along the lines I have suggested, it would seem to emerge that, far from this being a new epidemic, it shows every sign of being a well-established epidemic, and one which has been under way for at least 25 years. If so, it may well be that the current orthodoxy of booze-and-cigs causation has been horrendously mistaken all along, and a viral cause of cancer has been overlooked for at least 25 years, and quite possibly even 50 or 75 years. Which would be unthinkable. And so nobody is thinking it. Except me.

Perhaps the most percipient observation is to be found in the editorial:

We do not know where we are in the course of the epidemic of oral HPV leading to OPSCC…

Yup. Could be the start of a new epidemic, or the continuation of a very old one. We have no idea.

But what do I know? I’ve only been looking critically at this paper for a few hours today.

About Frank Davis

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21 Responses to Old and New Epidemics

  1. junican says:

    I cannot help but feel that, were these studies taken seriously and HPV found to be ‘the cause’ of many more cancers, the zealots would be out in force claiming that smoking, and only smoking, enables HPV to take hold.
    Stands to reason, dunnit?

    • Frank Davis says:

      I think that, with the HPV cancer theory, we may be watching the slow return of real science, after 60 years of smoking-related madness. But they’re having to tread very carefully, because their paymasters all truly believe that smoking causes all cancer (and heart disease, and everything else).

      Thanks to Harald zur Hausen, cervical cancer began to be regarded as just another virally-transmitted disease, and an HPV vaccine (Gardasil) was developed for it. But HPV didn’t just stop in the cervix. It’s crept out, and now it seems to have found its way to the mouth and throat. Next stop will be the lung.

      But they can’t tell the smoking-obsessed authorities that cancer has got nothing to do with smoking (or drinking). Nope. So instead they’re presenting HPV as a successor to tobacco. As smoking-induced lung cancers are dying out (thanks to the war on tobacco), HPV is becoming the new cause of cancer, picking up where smoking left off. The Old Guard of smoking-obsessed nutters are being told, “Well done! You beat the tobacco demon! But we’ve found this brand new cause of cancer which has come along in the last few years. This is the new demon, which a new generation of doctors must fight, just like you guys fought tobacco. Here, I’d like to award you the Order of the Golden Cigar in honour of all the work you’ve done over the past 50 years.”

      In this manner, they’ll slowly prise the dead fingers of the antismoking loonies from the helm, and retire them with honour. And after a 50 year (or 75 year) hiatus during which no meaningful research into cancer whatsoever was conducted, cancer will begin to be treated (and quite possibly cured), as real science at last begins to be applied to it.

      It’s crazy really. We have all these diseases which are almost all known to be caused by some virus or bacterium or deficiency, and all these nutters came along and started claiming that they were caused by, of all things, … TOBACCO SMOKE! How did anyone ever begin to believe such nonsense? How did medicine manage to go backwards for 60 years?

      But it seems it did. And it wasn’t just medicine that went backwards.

      • Mike F says:

        Re cervical cancer.

        The World Health Organization http://www.who.int/tobacco/research/cancer/en/ (2011) has the following to say (under the heading of Urinary bladder & kidneys): Tobacco’s effect on cervical cancer was only recognized recently, in part because women who smoke may have other risk factors for cervical cancer, particularly exposure to human papilloma virus which increases risks of cervical cancer. Nevertheless, there is now general consensus that cigarette smoking increases risks of cervical cancer, particularly among women smoking as many as 40 cigarettes daily, and is responsible for approximately 30% of cervical cancer deaths in the USA. (No citation for the 30% claim.)

        I checked several of the U.S. Surgeon General’s reports. Weirdly, the 1980 report (specifically about women) doesn’t mention the subject of cervical cancer except for two brief footnotes on Carcinoma in situ. The 1982 report (specifically about cancer) page 141 finds conflicting results and doesn’t reach a conclusion. The 2004 report (pages 167 to 170) rectifies this situation by concluding that (surprise!) “The evidence is sufficient to infer a causal relationship between smoking and cervical cancer.”

        Chris Snowdon did a nice post (October 8, 2010, Nuns, prostitutes, witches and toads) about female smokers being more likely to have more sexual partners and therefore are more likely to be exposed to the HPV virus. The 2004 SG report (page 170) doesn’t agree: “The most recent studies consistently show that smoking is associated with an increased risk among HPV positive women. The increased risk is of a moderate strength and not likely to be explained by confounding by sexual behavior, as all women were HPV-positive in these analyses. Dose-response relationships were also demonstrated. Finally, in 2002, IARC concluded that there is now sufficient evidence for a causal association between cigarette smoking and cancer of the uterine cervix (IARC 2002).” I haven’t read the original studies, but I’ve never been impressed by the SG’s “evidence” on anything.

        Influenza is also a smoking related disease (as is just about everything else). Why should the HPV virus be any different?

        Anti tobacco screwballs cornered the market on cancer “research” 60 years ago, and they’ve been reaping the profits and expanding their empire ever since.

  2. Hi Frank. Also in stomach cancer Helicobacter pylori bacteria is implicated. One person said it is found in up to 80% of cases.

    “A Canadian study found that the increased risk was greatest in people infected with Helicobacter pylori bacteria.”

    I also have a paper which may finally nail that passive smoking causes lung cancer.

    http://cancerhelp.cancerresearchuk.org/type/stomach-cancer/about/stomach-cancer-risks-and-causes

  3. Kin_Free says:

    You may find this interesting.

    http://discovermagazine.com/2009/new-science-of-health/big-idea-beat-cancer-cut-health-care-costs-80-percent/

    D: How much cancer is caused by viruses or other infectious agents?


    PE: If I were going to put my money on it, I would bet that by 2050—hopefully earlier—we’ll have found that more than 80 percent of all human cancer is caused by infection. The number could be as high as 95 percent. In 1975 it was considered to be zero.

  4. The Man With Many Chins says:

    So the cure is to stop licking dirty flaps?

  5. Brigitte says:

    On reading
    http://jco.ascopubs.org/content/early/2011/10/03/JCO.2011.36.4596.full.pdf+html

    N=271. Excuse me?

    Ah, at the very end one can read.
    Although all authors completed the disclosure declaration, the following
    author(s) indicated a financial or other interest that is relevant to the subject
    matter under consideration in this article. Certain relationships marked
    with a “U” are those for which no compensation was received; those
    relationships marked with a “C” were compensated. For a detailed
    description of the disclosure categories, or for more information about
    ASCO’s conflict of interest policy, please refer to the Author Disclosure
    Declaration and the Disclosures of Potential Conflicts of Interest section in
    Information for Contributors.
    Employment or Leadership Position: None Consultant or Advisory
    Role: Brenda Y. Hernandez, Merck (C); Maura L. Gillison, Merck (C),
    GlaxoSmithKline (C), Amgen (C), Bristol-Myers Squibb (C) Stock
    Ownership: None Honoraria: Brenda Y. Hernandez, Merck Research
    Funding: Brenda Y. Hernandez, Merck; Maura L. Gillison, Merck Expert
    Testimony: None Other Remuneration: None

    It’s crazy really. We have all these diseases which are almost all known to be caused by some virus or bacterium or deficiency, and all these nutters came along and started claiming that they were caused by, of all things, … TOBACCO SMOKE!

    This is probably their biggest contradiction.
    Using common sense:
    with all the proclaimed “poison” in tobacco smoke, how can any virus or bacterium survive?
    What is the rate of cancer in people who have stopped smoking?

    Hell will freeze over before they will admit that active smoking (!) might well be a prevention of bacterial/viral induced cancers.

    HPV has been of particular interest since the 1950s on the – then baffling – discovery of the “immortal” HeLa cell line.
    http://www.ncbi.nlm.nih.gov/pubmed/16955216
    http://www.smithsonianmag.com/science-nature/Henrietta-Lacks-Immortal-Cells.html

    However, the drive for vaccines appears to have a drawback:
    http://thetruthergirls.com/Immortal_Cell_Lines.html
    http://curezone.com/art/read.asp?ID=12&db=12&C0=735

    Time to ditch the invitation for flu jab and light up instead.

  6. Brigitte says:

    sorry – although posted, the continuation (HPV, HeLa cells + vaccination) does not show. (?)

    • Frank Davis says:

      They were all in the spam folder. I’ve extracted them all. Maybe a bit of duplication.

      • Brigitte says:

        Sorry – could you please delete the duplicates? It looks like the first post went wrong and I re-posted my comment in 2 parts then… *Apologies*

        ——

        [I deleted all of them except the first, which contained everything that was in the others. Frank]

  7. Frank Davis says:

    Following up Mike F’s reference to a piece by Chris Snowdon, Chris wrote:

    Smoking, like herpes, was not the cause of cervical cancer, it was simply more common amongst women who were sexually active and, therefore, more likely to be infected with HPV. Had the Italian doctor looked at tobacco use, he would have observed that smoking was more common amongst prostitutes than amongst nuns. He might also have noted that prostitutes were more likely to drink alcohol, have children and be atheists. But none of these things caused cervical cancer; they were just more common amongst prostitutes. The statistical correlations were real, but they were meaningless until the nature of HPV was understood.

    It reminds that, while watching Prohibition a few days back, I noticed in passing that it was said at one point that men and women started sleeping together during Prohibition (and I assumed it was meant that they weren’t married). And during Prohibition, they were drinking and smoking together in speakeasies. Drinking, smoking, and sleeping around all went together. They were part of a package.

    If sexually-transmitted HPV was the real culprit for most forms of cancer, Prohibition may well have seen something of an explosion of HPV infections, and of cancers developing 20 or 30 years later among people who smoked and drank and slept around.

    But then it wasn’t as if sex was invented in 1920. If there was a rise in HPV infections, there would also have been a rise in other STDs, like syphilis. I wonder what the incidence of these other STDs was during this period?

    Chris Snowdon on HPV:

    It was a rare breakthrough in the war against cancer. It came about thanks to advancements in our understanding of biological science and was facilitated by the development of new drugs. It was, if you will, an ‘old-fashioned’ way of dealing with a public health problem. It owed nothing to the army of epidemiologists who were dominating popular science, nor to the proponents of the fashionable belief that cancers were caused by tobacco, diet, alcohol and environment. Not only had the social theorists missed the mark, but their preoccupation with smoking had sent researchers on a wild goose chase for more than two decades.

    The ‘old-fashioned’ science was real science. The new-fangled epidemiologists with their statistical associations had ceased to do real science, and started chasing will-o-the-wisps.

  8. This guy has done a great job when it comes to HPV & Smoking

    It’s worth having a look

    http://www.smokershistory.com/

    • Brigitte says:

      It would seem that I have been tasking more than one step at the time. It has been well known for quite a number of years that HPV (type 16 and 18 if I remember correctly) DNA has been found in 70% of cervical cancer.

      And HPV IS contagious! (Like it or not, people!!!)

      However, why is such utter, utter rubbish

      http://www.medicinenet.com/oral_cancer/page2.htm
      Oral cancer: Who’s at risk?

      Doctors cannot always explain why one person develops oral cancer and another does not. However, we do know that this disease is not contagious. You cannot “catch” oral cancer from another person.

      Research has shown that people with certain risk factors are more likely than others to develop oral cancer. A risk factor is anything that increases your chance of developing a disease.

      The following are risk factors for oral cancer:

      Tobacco: Tobacco use accounts for most oral cancers. Smoking cigarettes, cigars, or pipes; using chewing tobacco; and dipping snuff are all linked to oral cancer. The use of other tobacco products (such as bidis and kreteks) may also increase the risk of oral cancer. Heavy smokers who use tobacco for a long time are most at risk. The risk is even higher for tobacco users who drink alcohol heavily. In fact, three out of four oral cancers occur in people who use alcohol, tobacco, or both alcohol and tobacco.

      still being published? A blatant abuse of science!

      Could it be that this
      http://blogs.menshealth.com/health-headlines/heads-up/2011/04/05
      is just hugely unpopular? (If this is the case, blame something other than smoking – at least nicotine has an antimicrobial effect!)

  9. harleyrider1978 says:

    GaryK if your lurking around here perhaps you can crunch a few numbers on this:

    Figuring Your Odds Of Premature Death [originally posted 1999-01-24]
    Posted on October 7, 2011
    by mogasp| Leave a comment
    http://mogasp.wordpress.com/2011/10/07/figuring-your-odds-of-premature-death-originally-posted-1999-01-24/#comments

    Involuntary Smoking [“Secondhand smoke”]: 1 in 55.
    In other words, smoking is like taking a double-barrelled shotgun with one barrel loaded, holding it to your head, and pulling the trigger during your smoking lifetime, and paying upwards of $30,000 or more for the privilege.
    Premature death from involuntary smoking is about twice as likely as dying in a car wreck and six times as likely as being murdered. TV is full of mayhem caused by motor vehicles or handguns. When was the last time death from someone else’s tobacco smoke was portrayed or reported on TV?
    HOW THE RISKS ARE CALCULATED
    Killer Asteroid: The two Air Force officers arrived at their 1 in 25,000 chance of a person being killed by an asteroid during their lifetime as follows:
    The earth gets hit by an asteroid big enough to cause a global catastrophy once every 500,000 years, so the odds of that happening in any given year are 1 in 500,000. Assuming such an impact kills 25% of the Earth’s population, that makes the risk from an impact 1 in 4. The odds of any individual dying from an asteroid strike in any given year are 1 in 500,000 multiplied by 4, or 1 in 2 million.
    But since we live on average 75 years, these odds must be multiplied by 75 to obtain the risk of premature death in any given year. Hence the lifetime odds of dying from an asteroid strike is 75 in 2 million, or 1 in 25,000.
    Active Cigarette Smoking: For smokers, who number about 50 million adults, the number of deaths is estimated at over 400,000 each year, so the annual risk is about 400,000/50 million = 1 in 125. Since most smokers don’t start until they’re about 14 we should calculate the 75 year lifetime risk over 75-14 = 61 years.
    So the lifetime risk is 61 x 400,000/50 million = 61/125 = 1 in 2.
    Involuntary smoking/SHS: The total U.S. population was estimated as 266,499,365 on January 1, 1997, so the total number of nonsmokers is 266.5 million less 50 million = 216.5 million. The estimated number of deaths among nonsmokers each year due to involuntary smoking is 53,000 (1), so the lifetime risk of premature death = 75 x 53,000/216.5 million = 75/4,085 = 1 in 55.
    CONCLUSION
    One good thing about the odds from a smoker’s viewpoint: they really don’t have to worry about any of the other risks that plague the rest of us! [Might be a good reason for having an all-smoker military. When bullets and shells are whizzing by they can laugh it all off, secure in the knowledge that it’s only smoking they have to fear!]
    For the rest of us, it’s difficult to avoid tobacco smoke, which is still commonplace in Missouri, and you often don’t even know it’s present. And as Missouri GASP has been vainly claiming for years now, based on the kind of numbers above, we should be giving active and involuntary smoking much more attention than we do.
    (1) Published peer-reviewed papers. Number accepted by American Heart Association, the majority of such deaths being attributed to heart disease, not lung and other cancers.
    NOTE: We’d like to add to the utility of the above RISK LIST. If you have reliable sources of premature deaths due to other causes, such as dioxin, low level radioactive waste, low frequency electromagnetic radiation* [ARE there any estimated deaths due to these causes?] please let us know of them.
    * For Missouri/St. Louis, not just the U.S. _______________
    Copyright Martin Pion © 1997

  10. Gary K. says:

    So the lifetime risk is 61 x 400,000/50 million = 61/125 = 1 in 2.

    1.) The 400,000 includes deaths to ex-smokers and there are more of them than there are current smokers.

    2.) Over the course of 61 years, your group of 50 million smokers will have changed quite a bit.

    Many will have died, many will have quit smoking, and there will be new adult smokers every year.

    This was just more anti nonsensical BS.

    • Gary K. says:

      Also, data from the CDC shows there are NO smoking related deaths below the age of 35.

      If most smokers start at the age of 14, they will have at least 24 years of ZERO risk of a smoking related death.

  11. Gary K. says:

    Also; risk/probability, is not cumulative.
    If you flip a coin and it comes up ‘tails’, that coin is not 100% certain to come up ‘heads’ on the next flip.

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