National reporting on the numbers is not available right now from any of the big institutions like the NCI or CDC. Since the rate of incidence is growing faster in young HPV positive people, the lecturers and researchers that I talk to are starting to differentiate between them by age groups. In people under 50, and definitely in those under 40, the percentage of HPV+ incidence OSCCC is estimated to be over 50%. This is only being tracked consistently at about 5 institutions, yielding that belief and trend line. So this is not an absolute number, but anecdotal in nature. In people over 50, HPV is much lower as a cause, and what you quoted is about right 20-25%.

Remember that tobacco carcinogenisis is a more protracted process, and decades of tobacco use, and the subsequent cellular disruptive changes and eventual malignant progression, takes decades to occur. So it is not unexpected that because of this, the tobacco group tend to be older.

The mechanism of cellular function disruption caused by the virus is much more rapid, and it requires fewer aberrations in the cell to take place for malignancy to fully develop. The primary instigating keys are the virus's expression of oncoproteins E6 and E7. These two proteins specifically target two genes, that when damaged, move the cell quickly toward full malignancy. E6 targets gene P53 which controls programmed cell death, a normal process in our bodies. With that gene destroyed the cell becomes immortal, one of the simplest definitions/characteristics of a malignant cell. E7 targets gene RB, which is involved in immune system signaling, and effectively hides the aberrant cell from being destroyed by normal immune system processes. This all happens on a very short (compared to tobacco carcinogenisis) time line.

Unknown primaries, I am finding are often just poorly reported and misdiagnosed HPV etiologies. Remember that in much of the medical community the adoption of the knowledge of the role of HPV is still behind the cure I am sorry to say. This does not mean that there are not plenty of REAL unknown primaries. People that I work with have differing opinions about all this. Most would agree that in as many as 5-10% of all cases, we just do not know what causes OSSC. There is some belief that when a positive node is found, that inadequate means are used to find the primary. Here's a real world, but anecdotal example. Hopkins was seeing a fair number of people present with a painless, fixated, indurated node in the neck that tested (through FNB) positive for SCC, but the oral cavity was completely occult when viewed by oncology professionals. They began to do prophylactic bilateral tonsillectomies in these patients, and in that group - 70 % were found to have SCC in the tonsil - that was completely occult in the oral cavity. No longer an unknown primary.

As you can imagine as this tonsillar trend continues to grow, it causes a huge problem for dentists and doctors that do not palpate the neck as part of their oral cancer exam, or do not know how to do this properly. There are obviously tricks (techniques) to doing this correctly that anyone can be taught in 15 minutes, such as the position you put the head in to cause the SCM muscle to protrude so you can run your fingers down each side of it feeling for hard nodes. In these cases there is still an opportunity to find relatively early and survivable disease even with a neck met, as it appears that a stage two or three HPV+ disease may not be a dangerous as the same stage disease from tobacco when it comes to treatment response and survival. When I lecture about all this I am really careful to state that I am talking about what we now consider to be multi-center anecdotal evidence, and published data does not exist.

A genetic/heredity connection has not been proven and published. That does not mean it does not occur, as we have seen in our own family here on the boards. But it is rare in comparison to the other etiologies, and the incidence rate, combined with our poor method of tracking these kind of things, means that it might be decades before we have a definitive answer to how that genetic transfer might take place, and in what population of people, with what genetic make up.