Comment by epcoa
13 hours ago
> 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 It’s outdated, missing a control *, and it’s pretty well accepted that just finding a bystander HPV DNA fragment around somewhere is not conclusive of causality.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.
This has nothing to do with "liking" or appeals to emotion. The fact is that paper does not have a control and the methods are not sophisticated enough to determine causation.
"The other citation from the second link seems to be a paper which doesn't say 3% it say". Yes it does dude. You need to read the actual results from the paper more carefully: "Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%)." Ie 2.8% (~3%) were considered true HPV negative by this testing.
They're going from 8.8% (in that particular admitted biased dataset) to still 2.8%, the wording of the conclusion is wonky, but the results of the paper are overall consistent. You're taking that quote out of context.
In that same paper it says: "Our results are in accordance with The Cancer Genome Atlas Research Network (CGARN) ‘Integrated Genomic and Molecular Characterization of Cervical Cancer Study’, which used next-generation sequencing to characterize primary cervical cancers. The CGARN study found 95% of primary cervical cancers were HPV-positive and 5% HPV-negative."
Which is one of the primary sources for the 5% figure.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5354998/
In any case these are both order of magnitude more than 0.3%
I'll agree 8% worldwide is high (though since environmental factors and genetics both play a role in both HPV-positive and negative cases), these incidences can vary throughout the world or within certain subgroups, and if you manage those groups that matters.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11075765/
GAS is a clearly known cervical adenocarcinoma not related to HPV, and it accounts for 20% of all cervical adenoca in Japan, which overall places it close to 5% of all cervical cancer diagnoses there, just for this subtype.