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.


Brian, stage 4 oral cancer survivor. OCF Founder and Director. The first responsibility of a leader is to define reality. The last is to say thank you. In between, the leader is a servant.