In today’s article, we will focus on cancers of epithelial origin, carcinomas. Let’s start by answering the question I left from my last column: Why don’t children get carcinomas? Recall that epithelial tissue forms the exterior of our bodies and thus is in contact with the world at large, with our external environment. That is true not only for the epithelium of the skin, but equally true for the gastrointestinal tract, which is exposed to what we ingest, and to our respiratory tract, which is exposed to what we inhale. Most cancers are caused in part by environmental carcinogens (in concert with genetic factors) and therefore epithelial tissues have dramatically more exposures than the more internalized connective tissues. Evolutionary selection would perforce have made epithelial cells more resistant to carcinogenic agents than connective tissue cells, which are more protected. The end result is that it takes much longer for cancer to occur in an epithelial cell—usually not until middle age or older.
As discussed last week, epithelial cells are confined to the area above the basement membrane, while connective tissue cells are below it. When a biopsy is taken from any organ and examined under the microscope, the pathologist occasionally will see epithelial cells below the basement membrane in the area reserved for connective tissue. This is a no-no; the basement membrane’s role as a barrier is inviolable. If this does occur, it is known as invasion and is the hallmark of a malignant epithelial cell or carcinoma; the defining characteristic of a carcinoma is invasion. If you read a pathology report of a cancer biopsy, the pathologist will almost always use the term invasion in some fashion to highlight that it was present.
Sometimes the pathologist will see cells in the area above the basement membrane (the epithelial area) that look like carcinoma (malignant epithelial) cells. Malignant cells have a distinctive appearance, so a competent pathologist can recognize them visually even in the absence of invasion, but if there is no invasion, if they are above the basement membrane, they are not malignant. So what gives? This phenomenon is known as carcinoma-in-situ or CIS. The transition of a cell from normal to malignant takes many steps over many years, and therefore it is not surprising to learn that at some point one may observe some of the intermediate cells in the tissue. CIS is presumably the last step prior to full malignancy (invasion), waiting to invade.
It is important to appreciate that CIS, in the absence of invasion, is not cancer. It should be 100% curable and non-fatal. We come across CIS in the cervix, breast and colon. If removed or treated, the cancer may be prevented.
In the first half of the 20th century, cervical cancer was the No. 1 cancer among women in the U.S. In 1945, George Papanicolaou, a Greek pathologist at Cornell Medical School, introduced the Pap test for screening women for early cervical cancer. The secret to its efficacy is that it detects cervical CIS which, if found, can be readily treated and cured. The result is that the woman never gets invasive cervical cancer in the first place. The test was rapidly and widely adopted with remarkable success—thus, there are ongoing recommendations for cervical screening (recent guidelines have been augmented by testing for human papillomavirus as well). Because of the Pap test, the incidence of cervical cancer in the U.S. fell by 85% and invasive cervical cancer is now a fairly uncommon disease. And this despite the fact that it remains a major cancer among women worldwide where the screening paradigm isn’t followed as faithfully. Parenthetically, the recent introduction of vaccinations for human papillomavirus (HPV) will probably make the Pap smear an anachronism in the future, as cervical cancer is caused by HPV and so the vaccine will, in time, mostly eradicate the disease.
It seems odd that the first cancer I address in a Jewish newspaper is cervical cancer. In 1901, an article in the Lancet commented on how cervical cancer “was seldom or never met with amongst the numerous Jewesses’’ who were seen in the local hospitals in London. Many subsequent studies have confirmed that Jewish women have a rate 10-20% that of non-Jews and likewise the rates in Israel have consistently been reported as extremely low among Jews (both Ashkenazim and Sephardim) as compared to their Arab counterparts. The reasons for this have never been fully clarified.
One initial hypothesis was that circumcision in the male partner was protective. However, studies among Muslims who were also circumcised as well as among Jewish women who had intercourse with uncircumcised partners did not seem to bear out this idea. A second hypothesis was a protective effect of the observance of niddah—Orthodox Jewish women have even lower rates of cervical cancer than non-observant Jewish women. It has been very difficult to get clear evidence for this one way or the other, but it does not seem to be a major factor.
One explanation that does seem promising is the lower prevalence of HPV infection among Jewish women. As noted earlier, cervical cancer is due to this virus, which is sexually transmitted. HPV infection rates are considerably lower among Israeli Jewish women than other populations. However, the recent loosening of sexual mores and resultant increasing levels of HPV infection have not led to increased cervical cancer rates. Others have suggested some common genetic features that prevent the disease. But a specific gene remains elusive.
Brathwaite, who originally noted the dearth of cervical cancer among Jewish women in 1901, suggested a possible explanation. He opined that it was due to the absence of bacon and ham in their diets. Maybe he had something there.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
By Alfred I. Neugut
