Based on the surface area of about 1.9 m2 and 3.5 million new cancers per year (Squamous cell carcinoma and basal cell carcinoma) the ectocervix has a very high cancer rate per m2 surface area: about 0.00075 m2 and about 12000 new cases per year. If you oversimplify and calculate the ratio of tumors/m2 in the USA you get enormous differences. Do these differences represent a higher susceptibility of the ectocervix or cervix compared to epidermis; or a different exposure to carcinogens (in case of the ectocervix HPV)?
Within the skin, are melanoma rare or more common than epidermal tumors taken into account the low number of melanocytes compared to keratinocytes (they at least are exposed to the same carcinogen)?
No scientific answer, but your hint to the human pappilom virus and other carcinogens seems very plausible. The high mitosis rate of the ectocervix and cervix cells together with external carcinogenes probably is another reason for higher cancer rates.
I¨m sorry to say that perhaps the question is wrong. It is not a matter of number of cells exposed but a matter of exposure.
Dear Mario,
that is a good point. But it appears that that is just a logical assumption without much data behind it? Cancer is an environmental disease and the more you expose yourself to carcinogens, the more likely it is you get cancer.
On the other hand, it is rarely (ever?) explored whether there are differences between tissues in regard to their susceptibility. I see the problem that are many (too many confounding factors: proliferation rate etc.) but is there a possibility that not all tissues are made the same way; and is there a data set to figure this out?
I think, the ectocervix is a tissue that has an enormous cancer rate. It is a tiny epithelium but is associated with a huge number of cancer cases. HPV must really like this region...
I looked at cancer rates for melanoma and non-melanoma skin cancers. They have similar exposure to carcinogens in a population. But is seems melanoma is more of a problem in European countries than the US. There is much more non-melanoma skin cancer relative to melanoma in the US than in Europe. Again one can argue: different carcinogen. the USA is far south, closer to the equator compared to Europe.
But you might in the end be right. This question cannot be answered the way I would like it to be answered due to the lack of appropriate data, even data from animal studies are hard to interpret...
Interesting question, Thomas.
In the epidermis we might speculate that we should count only the basal keratinocytes (which are likely the origin of both SCC and BCC in epidermis), not keratinocytes in all other layers since generally these move outwards and are shed.
Textbooks say that there is about one melanocyte per 10 basal keratinocytes in humans.
In the UK, the incidence of melanoma is about 1/10 that of non-melanoma skin cancer, although records are patchy for NMSC. So you could say that the incidence per cell is probably about the same for these two specific cell types. Although it may vary with the wavebands of UV. More UVB relative to UVA near the equator. And there is probably more evidence that UVA is a carcinogen for melanoma than for NMSC.
And of course for both these types it varies with skin colour, other genetic factors, and sun exposure.
(And I'd agree about HPV and the high cancer rate of cervical cells. It's not high in people not exposed to HPV. Keratinized epidermis is relatively protected against viruses.)
Thanks Dorothy. In the US the numbers for non-melanoma skin cancer must be skewed since the ratio between melanoma and non-melanoma skin cancer is very different here than in Germany, UK, Sweden etc. In Australia non-melanoma skin cancer may also be 2 fold overrepresented relative to melanoma. Looks like a mix of latitude/ UV radiation and skin type issue confirming the idea that Americans and Australians may be more fair-skinned and melanoma does not have the exact same etiology as keratinocyte cancers of the skin.
Using surface are basically is an estimate for the number of basal cells or cells able to initiate cancer. I think, I estimated that about 5% of these basal cells are melanocytes and the potential melanoma-initiating cells. I tried to include data on the third malignancy in the skin, Merkel cell carcinoma, but it is far too rare and I could not figure out their density in comparison to keratinocytes and melanocytes, or was it clear to me that Merkel cell carcinoma is derived from Merkel cells? They may be derived from K17-positive cells in these "domes" but the number of these K17+ cells still may correlate with the number of mature Merkel cells per square-meter. In the end it looks like cancer is an environmental disease for the majority of us and our genetic make-up favors or disfavors its development AND data on cell or tissue intrinsic factors playing into this are limited or non-existent.
I thought non-melanoma skin cancer rate per "stem-cell, progenitor or potential cancer-initiating cell" should be substantially higher than in non-melanoma squamous epithelia due to our recent loss of pelage. Without pelage we lost a major anti-cancer protection mechanism (not much UV goes through a well grown fur, I assume). Massive increases in pigmentation may have substitute for this loss in protection but then a second hit that produced "whites" must have exposed the original dilemma again? No? Yes? As said, the data to address this question don't seem to exist or include too many confounding factors.
In the end this question is distantly related to Pet's paradox: why don't have big, long-lived animals more cancer than little animals. Big animals have supposedly many more cancer-prone cells and also give these cells much more time to become aberrant. I speculated that in a recently messed-up tissue such as the skin, some of the mechanisms that may explain Peto's paradox may have been become exposed, assuming the epidermis is now more like the epidermis of a small short-lived animals. I think, this "hypothesis" had already some substantial flaws and never will make it to the state of a theory....
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