Any anecdotal or real data that would suggest improved outcomes for p16+ versus p16- tumors when PCR testing for HPV is negative for head and neck? Got a guy with laryngeal surface epiglottis primary (doesn't appear to be oropharyngeal) and p16 was ordered which came back positive but my understanding is this is meaningless and I'm still wondering if radiation is still a better prognosis in this subset since the G1 chekpoint is liley not working.
p16+ HPV-
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...tobacco causes a high mutational burden. If he smoked/used tobacco then the p16 positivity is likely just a causality of the mutation load.
The only reason HPV positivity is indicative of a better prognosis is because of a lower mutation load driven by the viral infection.
What would be interesting is if he was a never smoker but had an HPV negative H&N
Hope this helps,
The only reason HPV positivity is indicative of a better prognosis is because of a lower mutation load driven by the viral infection.
What would be interesting is if he was a never smoker but had an HPV negative H&N
Hope this helps,
p16 overexpressed in many tumors (reflects bypass/mutation downstream/in case of HPV inactivation of RB), and in those that it not, it p16/p21 is probably disabled mutation/epigenetic change in a micro rna or long noncoding rna etc. This pathway needs to be bypassed for cancer to overcome cellular senescence. (p16 is one of main markers of cellular senescence.) Head of NCI's entire career focused on this. Found this review of the issue by Adam Dickers group.
The meaning of p16(ink4a) expression in tumors: functional significance, clinical associations and future developments - PubMed
The CDKN2A gene is a tumor suppressor that encodes the CDK4/6 inhibitor p16(ink4a). Loss of this tumor suppressor contributes to the bypass of critical senescent signals and is associated with progression to malignant disease. However, the high-level expression of p16(ink4a) in tumors is...
www.ncbi.nlm.nih.gov
Getting rid of p16+ cells in the body- outside of oncology- is one of holy grails of aging. JAMA review last year.
Emerging Therapeutic Strategies for Aging, Cell Senescence, and Chronic Disease
Mayo group has some cool pics published in Nature and Science of making old mouse young and vice versa with genetically engineered approach to getting rid of p16+ cells.
Just finished David Sinclair's book: Amazon product ASIN 1501191977
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And when you are done with chemo/radiation, the head and neck normal tissue will be full of therapy induced p16+senescent cells. Body/innate immune system will kill many of them, but some will stick around to contribute to longterm chages/damage. not much thought being given to this in radiation biology, but outside of our field, you cant go one month without an article in Nature or Science about it. In the lab, senescence is often induced with radiation,
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I can't find the source, but there is a significant discordance of p16+/HPV- in NON-orpharynx primaries. I don't think there has been any evidence that HPV is prognostic in anything besides Oropharynx cancer (I vaguely remember seeing something at a meeting saying that it explicitly didn't matter in terms of clinical outcomes).
So for clear non-orpharynx primaries I don't care about HPV outside of for research purposes.
It doesn't matter if some of the cells are p16+ or HPV+.... they have to ALL (or at least most) be like that to have the better prognosis.
So for clear non-orpharynx primaries I don't care about HPV outside of for research purposes.
It doesn't matter if some of the cells are p16+ or HPV+.... they have to ALL (or at least most) be like that to have the better prognosis.
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Are people ignoring p16 in their smoker patients?
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you shouldnt, oropharyngeal p16 + smokers with > 10 pack years in Ang NEJM paper had control rates around 70%, in between p16+ nonsmokers and p16- patients where control was like 50% or less.
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Clearly you aren't going to include them in any de escalation protocols when they finally go mainstream though, right?
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As said above - smokers with HPV+ Ophx still had better outcomes than HPV- patients.
I will not EXTRAPOLATE de-escalation data to patients who do not meet the inclusion criteria of the trial that says it's OK (like if you want to do it based on HN-002 which used a cut-off of 10 pack years or the upcoming HN-005)
Remember that the original Ang cut-off was 10 pack years. That's 1 pack, per day, for 10 years. Certainly not impossible, given the 100-150 pack year patients I meet from time to time. But, I meet a fair number of people with HPV+ OPhx that have SOME history but not 10 pack years, and for them I classify them the same as a non-smoker. There likely is some granularity at a 5 pack year vs 10 pack year history but I'm not going to let that influence my treatment decisions if the trials say 10 pack years or less.
But, if a patient has 20 pack year history for example I'm not going to de-escalate even if HN-005 (uses the same 10 pack year cut-off as HN-002) says 60+Cis = 70+Cis.
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I thought > 10 year pack history excludes you from any protocol
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Fair enough, thanks for posting this. There does seem to be some levels of discordance between p16 and HPV in non-OPhx based on the abstract. But great to see that HPV may be prognostic even in non-OPhx.
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just head and neck, not other cancers
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I mean don't say that, there's data for it as a prognostic marker in vulvar:
Does HPV status influence survival after vulvar cancer? - PubMed
High-risk human papillomavirus (HPV) infection is essential in the carcinogenesis of a substantial part of anogenital and oropharyngeal cancers and has additionally been shown to be a possible predictive marker for survival, especially in oropharyngeal cancer. Studies examining the influence of...
www.ncbi.nlm.nih.gov
The Prognostic Significance of p16 Status in Patients With Vulvar Cancer Treated With Vulvectomy and Adjuvant Radiation - PubMed
p16-Positivity appears to be a prognostic factor for in-field relapse rates in patients with VSCC appropriately treated with adjuvant RT.
www.ncbi.nlm.nih.gov
Prognostic Significance of Human Papilloma Virus and p16 Expression in Patients with Vulvar Squamous Cell Carcinoma who Received Radiotherapy - PubMed
We have identified a favourable prognostic group in VSCC, with p16-positive patients showing improved outcomes. p16 has the potential to be a predictive marker allowing the identification of women more likely to have a favourable response to radiotherapy.
www.ncbi.nlm.nih.gov
Not sure where else it would be clinically useful? Cervical? 95% HPV+, Anal? Same thing. What other disease site is let's say > 5% and < 95% HPV-related?
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