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HPV Negative but P16 Positive

robinleigh's picture
robinleigh
Posts: 297
Joined: Mar 2011

Lots of pent up questions tonight. Doctors were surprised at this pathology but told us the P16 positive "trumped" the HPV negative. Still doesn't make sense to me. I thought P16 was a type of HPV. Anyone have this same outcome? They say there can be false negatives and maybe the HPV part was a false negative but the P16 was an even better indicator for responsive treatment. Odd...

Agatha
Posts: 62
Joined: Dec 2010

Hi there,

I am sorry that I cannot really help you with this, but I just wanted to share that I had the same outcome on my pathology. My doctor said that the tumour tested positive for P16, so he thought for sure I would test positive for HPV. When they tested for HPV (they tested for about 13 different types), they all came back negative.
I was really confused by this too because one minute I was told that I was HPV positive and the next I was told that I wasn't. Unfortunately, my doctor didn't give me much information on this, just that usually when people test positive for P16 they test positive for HPV. He said that I am just part of the 5% that they just don't know what caused it.

I was confused about what P16 was as well so I looked it up. I found information stating that P16 is a type of tumour suppresor gene. Now that you brought this topic up I think I will ask my doctor more about it. From what I understand, however, because I did not test positive for HPV, I would not be as responsive to treatment. But I am trying my best not to focus on this.

Take care,
Agatha

robinleigh's picture
robinleigh
Posts: 297
Joined: Mar 2011

I really want an answer to this. I did meet a pathologist who told me that I shouldn't worry because the P16 part actually trumps HPV positive. So I've been trying to believe the results are good news but I can't quite grasp it medically. We see his original surgeons tomorrow and I sort of feel like I have the right to understand it better. Maybe I will get an answer that will satisfy me. I'll pass it on if I do. I'm just very curious because the 2 results are just very odd.

Skiffin16's picture
Skiffin16
Posts: 8094
Joined: Sep 2009

Like everyone says a lot on here, everyone is different...but we do share at least one thing in common....we all have/had cancer in one form or another, or it's in our live.

I must admit that I hadn't really heard of P16 until this post. Nor it's relationship to HPV...I did see that P16 is related in someways to melonoma...

Anyways, there is a lot of information when you Google it...same with the relationship between HPV and P16.

Thoughts and Prayers,
John

Scambuster's picture
Scambuster
Posts: 975
Joined: Nov 2009

http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=35543

This site explains in a complicated way how HPV and P16 respond to treatments in a trial. Overall, it seems response does improve with p16 people. Please note most of these 'improvements' are based on 2 year or max 5 year outcomes. The Cancer industry uses a 5 year time line to measure our success rather than using 'actual cure'. I feel this is huge con and justifies the sometime indiscriminate use of Chemo. A new thread on this maybe.

The bottom line Robyn, don;t stress too much about this P16 stuff, and get cracking to do 'everything' you can to get rid of the cancer. I do not believe we can rely only on Surgery, Chem and Rads, and that we should apply every mechanism available to get rid of it, make cancers cells life hard and make it very unwelcome in our body's. Most long term survivor have done a few common things which have contributed to their winning the battle.

There are many other things you can do in this fight related to lifestyle, diet, nutrition and supplements. This is a very big topic.

You can PM me or go to my expressions page for further details. It is quite likely a change in diet will increase your prognosis far better than a few percentage points on a 2 year survival trial study because you are P16+. I think we often can't see the forest for the trees. Don't muck around, get serious about your body's health and ability to help with this fight.

Wish all the best
Scam

peerwani
Posts: 1
Joined: Aug 2011

Short Version:

HPV is a virus and p16 is one of the normal proteins within the cell that takes part in regulating the cell cycle and cellular division (replication).

When HPV integrates into a person's DNA, it dysregulates mechanisms within the cell. In particular, p53 and RB are inactivated. Both genes are tumor suppressors, the they are working the decrease the likelihood a cell will divide. Conversly, when they are inactivated, cells tend to proliferate or divide more frequently. But, the cellular machinery exist in a balance. RB expression is inversely related to p16 expression. As the RB expression decreases, p16 expression increases. Therefore, over expression of the p16 protein is used as a surrogate marker of viral integration into a person's DNA and subsequent dysregulation of their proliferation pathways.

Long/Detailed Version (the focus is on cervix because that is the organ we first came to understand the importance of HPV in the genesis of cancer):

http://www.diagnosticpathology.org/content/4/1/22

The intracellular targets for HPVs include a number of regulatory proteins such as cyclins, cyclin dependent kinases, cyclin inhibitors, and cell cycle-associated proteins. The HPV E6 and E7 oncoproteins inactivate the p53 and retinoblastoma protein (RB) tumor suppressors, respectively, leading to hyperproliferation and genomic instability [4-7]. RB inhibits the progression of cells into S phase and is regulated by cyclin D1 via phosphorylation. Progressive and prolonged phosphorylation of the RB protein leads to its inactivation and to a reduction of its growth suppressive activity [7,8]. This inactivation is mediated by the release of E2F-like transcription factors from RB, which allows the activation of CDK and transcriptional activation of target promoters [9]. The CDKN2A gene product, the p16INK4A protein, is a tumour suppressor protein that inhibits CDK4 and CDK6, which phosphorylate the RB protein. A reciprocal relationship between p16INK4A and RB expression has been observed [10]. The p16INK4A gene was found inactivated in a large percentage of tumor cell lines, suggesting that it was indeed a tumor suppressor gene [11-13].

p16INK4A overexpression has been demonstrated in cervical cancers as a result of functional inactivation of RB by the HPV E7 protein [14]. It has been reported that the HPV negative cell line C33A and HPV negative adenocarcinomas are p16INK4A positive, which indicates that a non-HPV dependent p16INK4A expression pathway may also exist [15,16].

A number of studies have demonstrated that p16INK4A may be a useful marker for squamous and glandular epithelial dysplasia in the uterine cervix [17,18]. Furthermore, expression of p16INK4A appears to correlate with the degree of cervical neoplasia [19,20]. It was also recently reported that p16INK4A immunostaining can be used for discriminating integrated from non-integrated HPV infections [18,21].

Skiffin16's picture
Skiffin16
Posts: 8094
Joined: Sep 2009

Ummm OK...

Caco
Posts: 1
Joined: Jun 2011

would really like to know how a patient who is P16 + but HPV negative develops an oral cancer, the readers digest version though?

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