Comment by epcoa
1 day ago
Spontaneous mutations? Which no matter how much you carve out modifiable risk factors will always be a thing. At least 5% of cervical cancers are HPV negative, so it's not even all the uncommon (not I would call "vast, vast" IMHO)
> Spontaneous mutations? Which no matter how much you carve out modifiable risk factors will always be a thing. At least 5% of cervical cancers are HPV negative
Random mutations causing cervical cancer essentially does not happen - as a sibling commenter writes, well-studied cases of this are so rare that they’re below our sensitivity of detection/technical error rates.
This is what I mean when I say we try to apply our intuitions to medicine - they’re not reliable and the truth is idiosyncratic.
Because our prior for cervical cancer being caused by HPV is so incredibly high, we would require overwhelming evidence to reject the hypothesis that any new case is due to HPV. There are ways to do this, and, should they be attained, would be published in a reputable journal based on their novelty.
> as a sibling commenter writes, well-studied cases of this are so rare that
And yet not a single cite in sight. A random commenter on orange site is not evidence
However I know the paper they are referring to - it is from 1999 in J Pathology, famous at the time, and it is woefully out of date.
> they’re below our sensitivity of detection/technical error rates.
Hogwash.
https://www.mdpi.com/2076-0817/14/7/668
> There are ways to do this, and, should they be attained, would be published in a reputable journal based on their novelty.
There are plenty of papers on HPV independent cervical cancer based on actual gene expression methods published in reputable journals in the last 30 years.
Where did you see 5%? I'm not an expert (though I think I know one) but the study I'm looking at says 0.3% - hence my "vast, vast". That's 3 patients out of 1000.
In that study they take cancer cells and check for HPV, get about 7% negatives which I'm guessing is what you're describing too, but they take those negatives and PCR them to figure out, well, OK, what was wrong with these cells and when you take the cells to pieces very often your assay goes oh, these instructions are HPV. So, you know, the cancer cells aren't "infected" with HPV but well the genetics are just HPV, the replication has gone haywire and tangled parts of HPV with the human cell instructions and now it's cancer.
Crucially we can assume that if you don't get infected with HPV this wouldn't happen. So HPV was still causal.
> Crucially we can assume that if you don't get infected with HPV this wouldn't happen. So HPV was still causal.
Nope. This is literally “correlation does not equal causation” 101. Based on the 0.3% I’m gonna guess you’re (either directly or indirectly) citing a famous, 1999 paper in J Pathology (Walboomers et al). It’s outdated, missing a control *, and it’s pretty well accepted that just finding a bystander HPV DNA fragment around somewhere is not conclusive of causality. We have much more sophisticated assays of gene expression. Try looking for review articles in the last 3 to 4 years rather than 30, the prevalence of truly HPV independent cervical cancer is not precisely characterized but it’s almost certain much greater than 0.3%.
https://www.mdpi.com/2076-0817/14/7/668
https://journals.lww.com/md-journal/fulltext/2024/10110/rese.... (3% to 8%)
That 3-8% cites two sources but...
One of those cited resources just keeps citing other people for a 5% risk, if they came up with their own number I didn't find it and I wonder why they'd cite somebody else in their own abstract without even mentioning they don't agree if somewhere in their work they do get a different number.
The other citation from the second link seems to be a paper which doesn't say 3% it says, and I'll quote: "The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations".
If they're to be taken for 3% the only way to get there is by disregarding that conclusion and deciding that false negatives count as true negatives. Reviewers should ideally catch that but didn't here.
As I said, I don't doubt it exists, but 8% seems insane and these citations did not persuade me I was wrong to say 0.3% based on the paper you don't like.
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