HPV 16 as a Determinant for Development of Cervical Carcinoma in Situ
HPV 16 as a Determinant for Development of Cervical Carcinoma in Situ
abstract & commentary
Synopsis: Women with carcinoma in-situ have higher human papilloma virus (HPV) 16 viral loads than controls.
Source: Josefsson M, et al. Lancet 2000;355:2189-2193.
In this study, 504 women with carcinoma in-situ (Josefsson and colleagues used the term "carcinoma in-situ" rather than CIN throughout the manuscript; they also call CIS "cervical cancer") were compared to 662 controls. The cases of CIS were confirmed by review of the histologic samples. Controls were appropriately selected. Josefsson et al state that "samples [were] collected during routine gynecological health checks" However, later Josefsson et al state that "Many of the cases’ smears were taken as part of a diagnostic work-up." Josefsson et al used PCR amplification to detect HPV 16 in the cytologic smears.
Women with higher amounts of HPV 16 DNA were much more likely to develop CIS than women who did not have high HPV 16 DNA values.
In the discussion section Josefsson et al mention that "high amounts" of HPV 16 DNA is "a major risk factor" for the development of CIS. They also state that "the amount of HPV DNA seems to predict the risk of developing cervical carcinoma before any cytological alterations are visible" Finally, they speculate that "the analysis of HPV DNA amount seems to have a higher specificity than the typing for presence or absence of HPV in smear samples."
Comment by Kenneth L. Noller, MD
I really do not know how this article achieved publication in such a well-respected journal. The one fact they report is that women with high HPV 16 viral loads are at greater risk for development of high-grade CIN than women without high viral loads. This is certainly not new information. In addition, because this is a case control study there is no way to predict the frequency with which women with high viral loads develop CIS. We are at the point of knowledge about HPV 16 and CIN that only prospective trials seem to be useful. Let me explain that more fully. Because all of the cases had CIS and none of the controls had CIS it is not at all surprising that the cases had more HPV 16 than the controls. Likewise, it is not at all surprising that the viral load was higher in at least some of the women with CIS than those who had no evidence of CIS. That is not terribly useful information. What we really want to know is the frequency with which a woman who has a high HPV viral load develops significant CIN. Case control studies will not be able to provide useful data concerning this vital piece of information.
There is also one additional item in this article which bugs me. Throughout the article Josefsson et al refer to the cases as women who have "cervical cancer." Carcinoma in-situ of the cervix is very different from "cervical cancer." Cancer implies invasion of the underlying tissues. CIS does not. I am quite surprised that the Lancet editors allowed this obvious mistake to be made in this manuscript.
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