With multiple partners you obviously increase your risk of acquiring HPV but most likely your immune systems clears it and then you reacquire it and it gets cleared, etc, etc until one time it doesn't get cleared and you end up with HPV+ cancer. Why that happens is still a mystery. Men and women pass HPV around like any other virus tied to "sexual" activities (including kissing) but to try and pin point one possible exposure and then say THAT is the one that caused me to get my cancer is ludicrous. IMO

I agree 100%

This in reply to Brian, forgot to quote:

Brian, if you're continuing to have pain or discomfort it's a good idea to get yourself checked out at a Comprehensive Cancer Center (CCC). Here's a list:

http://oralcancerfoundation.org/resources/index.htm#centers

David2

My husband was diagnosed at HPV Negative but P16 Positive. I don't understand that at all. It doesn't make any sense to me. Can anyone explain that?
Robin

Various markers have been sought for more than a decade to early identify individuals who are in the beginning process of malignant transformations of cells to oral squamous cell carcinoma.

Tumor suppressor genes/proteins have been the most obvious to look at and include P53, RB, and P16 among others. Each one of these controls various cell functions. Remember that we have only recently unraveled the human genome and what most genes do in detail is largely unknown. Some like P53, have been heavily studied for decades, and we know for certain that it controls apoptosis or normal programed cell death, or the normal replacement of old cells in your body with new ones which is going on every day of your life. This also makes it a very effective tumor suppressor gene as oral cells for example, die rather quickly in the overall scheme of things (their life in the oral mucosa is about two weeks) and therefore progression to full malignancy of a cell has to follow a different, fairly rapid route (in cellular biology terms, not chronological) which starts with the creation of cell immortality.

HPV is an expert at this. It expresses an oncoprotein called E6 which targets P53 specifically, and destroys or inactivates it and does nothing else. HPV16 expresses another oncoprotein E7, which takes out RB, another important tumor suppressor. So as a virus, it is a very elegant design, allowing it to live inside a human cell with all the reproductive functions etc. intact, and at the same time immortalize and protect the cell from the immune system. People think that my use of the word elegant to describe the design of HPV16 is glorifying a horrible thing, but in my opinion elegant design is possible even in very destructive things.

P16 has been looked at for about a decade and early research on it showed that the p16 tumour suppressor gene is known to be involved in regulation of the cells life cycle. p16 expression in sequential histological stages of oral squamous cell carcinoma has been observed and reported.

In the mid 2000's thinking changed some. p16 is found significantly increased in hyperplasia, sharply decreased in dysplasia, (this finding seemed incompatible with the next thing) decreased in the subsequent stages of oral carcinogenesis. Conclusion: Inactivation of p16 occurs at the early stage of oral mucosal dysplasia in the multistep process of oral tumourigenesis, but not in the final stages of transformation. Therefore, p16 may be considered as a useful prognostic marker for the beginning progression of oral cancer.

The interesting thing they later found in other research, was that in late stage SCC's it was a factor in exofitic (VC oral cancers) ones that are raised in papillomas or flame shaped, (above the tissue growths), so some correlation between HPV16 and P16 seems to be at play.

There is much debate about what all this means in finite terms, and lots of speculation from researchers with grossly different findings in what are mostly animal studies and small human studies. Some say that it NOT a reliable marker for oral cancers, others the opposite. We will know soon. If it is indeed a marker that has value, recent research from about two years ago shows that the good news is that the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, (which is that there is a survival advantage) also shows that p16 identifies a larger group with an improved prognosis as well. The HPV negative, but p16 positive population also has a better prognosis compared to patients with HPV neg/p16 neg tumors. So clearly (really? after reading all that) it has prognostic value, some of which is good to hear, some of which is on the not so good side of things.

Now if all this has you thoroughly confused, join everyone in the research community who are still really trying to put this peg firmly in a hole that we can take to the bank.

I have answered your question on this thread which is about something else. Please - when you have a new question open a new thread for it so that people can follow you, and it doesn't muddy up the conversation that is already gong on in the thread. This in posting board parlance is called hijacking a thread, which is not good web etiquette. But as a new poster with only one post, I thought that you needed a chance to find your (at least some kind of) answer, and then open up a new thread if you what more information about your husband's situation. One of the admins will move this when you do.

Wow Brian, Thank you for that. I would VERY much like to print that out and give it to my RO to give to his patients. He's 35 years into this and I'm sure he knows what you just said but he never told me. Not like that anyway. I doubt it for lack of being able to explain it either. He probably just doesn't want to take the time thinking....what do they care or need to know as long as I cure them. Let me know. I can do it with or without your name. And if for some reason you don't want me to you don't need to explain. I totally get it

Remember that your doctors are REAL doctors, and I am a science nerd. The reason that they probably didn't go into this in detail with you is that the absolute meaning of it all may still be ambiguous. Also remember that I do not have intimate knowledge of the patient, I do not have a lot of fancy letters after my name (which you have to earn) and they may have particular reasons for not telling you that neither of us are aware of. Most doctors will tell you anything that you really want to know, and if you had pressed them as to the meaning of a P16 issue, they likely would have taken the time to explain it in some form to you. Perhaps even more succinctly than I, and with possibly something more current from the research files.

I am sure that with 35 years of experience, he has forgotten more about this than I will likely ever know.

I just thought that you deserved an answer, and I knew just enough about this to be give you a starting point to form some good questions from it for your doctors.

Please do not walk away from this thinking that I am any kind of "expert" on any of this, I certainly am not. But now you know what I have been taught or read, and there may be much more to this than appears in my previous post.

Okay, so now I understand why the J's RO didn't want me asking questions about the pathology report!!!

I did enough research on-line to find that HPV will show up in Branchial Cleft Cysts which makes it much harder to diagnose a SCC HN from a BCC (which, by virtue of its name, IS a neck issue.) It is either a benign congenital cyst or it is oral cancer. Could there be a worse differential diagnosis?

I was thinking, in error, that p16 positivity and HPV+ status were interchangeable. It is very confusing. There is HPV+, there is also having an active HPV virus, and there is p16 positivity. I know the test for the presence of HPV is indicated by a p16 cell stain. So...since I am now on the good ship Confusion...and have made sure everyone is invited along for the cruise...I'll stop trying to figure it out now! I need a Motrin.... :S

2007 they thought it was a worthy marker of cell progression to malignancy
http://ar.iiarjournals.org/content/27/2/979.full.pdf

2008 they thought that it was a good prognosticator of better survival, useful enough to suggest that increased aggressive treatment in patients with its expression wasn't needed
http://cebp.aacrjournals.org/content/17/2/414.full

2009 they thought it didn't mean crap and was an unreliable marker
http://www.ncbi.nlm.nih.gov/pubmed/19192055

2011 they found p16 may not be useful for distinguishing hyperplastic oral epithelium from dysplastic oral epithelium (no predictive value)
http://www.scielo.br/scielo.php?pid=S1806-83242011000100007&script=sci_arttext

And in a review of a ton of articles (a three page bibliography), the Brits found the
P16 regulatory gene has been extensively studied (no shit) and is a promoter of hypermethylation common in OSCC (p16:76%) however, no significant correlation with clinicopathological characteristics or prognosis has been observed. Further, these epigenetic aberrations have also been shown in �normal� and dysplastic oral lesions, (which mean that it is worthless as a marker) BUT after stating that clearly they go on to conclude the exact opposite, that it may be involved in the early stages of carcinogenesis and related to exposure to alcohol and tobacco. So separate for the whole HPV issue they conclude that it is more tied to the tobacco carcinogenesis pathway.
http://research-archive.liv.ac.uk/288/2/05-047-draft9-26-5-05.pdf

I could go on here, but in the end, this is the contradictory nature of research, interpreting what it means, whose studies have bias in them, whose have too few participants or samples to be meaningful, and so much more BS.

MY OPINION, stated above is that after reading these things about p16 till I am almost blind for 5 years, is stated in the previous post:


There is much debate about what all this means in finite terms, and lots of speculation from researchers with grossly different findings in what are mostly animal studies and small human studies. Some say that it NOT a reliable marker for oral cancers, others the opposite. We will know soon. If it is indeed a marker that has value, recent research from about two years ago shows that the good news is that the prognostic significance of tumor HPV status in oropharyngeal cancer treated with chemoradiation, (which is that there is a survival advantage) also shows that p16 identifies a larger group with an improved prognosis as well. The HPV negative, but p16 positive population also has a better prognosis compared to patients with HPV neg/p16 neg tumors. So clearly (really? after reading all that) it has prognostic value, some of which is good to hear, some of which is on the not so good side of things. It is not a stand alone prognosticator, it does not significantly impact treatment decisions at major institutions, and depending on which researcher you listen to with glazed eyes over these cell modulating proteins you will come away with a different answer today. Tomorrow is going to be different because they have been beating this marker to death looking for a Holy Grail of prognostic opportunity, and they soon will thumbs up or down it as a meaningful component of the question.

I think it is going to be just another small piece of the tumor suppressor protein/gene puzzle and never be a stand alone marker of significance, without considering the many other contributions of the many other cell regulators (p53, RB etc.) at the same time.

So...I won't be able to resist reading the publications. I have problems not looking at train wrecks and car accidents, too.

More than one of J's pathology reports stated that a positive p16 stain could be used as a DIAGNOSTIC for SCC HN in the event that it was hard to make a firm diagnosis based on the cell samples(!) One of those reports referred to a study of SCC HN by one of the pathologists who consulted on J's diagnosis. (!?!) Nevermind that I found another study that pretty much refuted his study a year after it was published, nevermind that his study was on FNA's only, nevermind that he also co-authored a study on cardiac transplants, nevermind he just got his pathologist's wings in 2007. This was one of the experts selected by the original diagnosing pathologist!

Thank you Brian...and you are right about the studies. It's Garbage In, Garbage Out in most cases. HPV research is a Pandora's Box 'o Fun!

Don't get me started on EGFR (sorry, sorry, sorry for mentioning it!) and Erbitux.

More Motrin...no! Where's those "Mother's Lil 'elpers"?!?