In light of recent acceptance to a summer program where I will be working in immunology, I wanted to choose an article relevant to reproductive health and immunology. The first place I turned to was the Journal of Reproductive Immunology. This seems like a copout, but I found a very interesting and recent article for the lab meeting entitled "Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium" by Hwang et al in 2011.
It would be wonderful if human variation was always taken into account, particularly when discussing reproductive health. This is exactly what the researchers from UCSF aimed to do and why this article was a refreshing read. It is known that women aged 15-24 have the highest rates of Sexually Transmitted Infections (STIs) and is commonplace in the medical community to associate STIs with risky sexual behavior. The study looked at cervical epithelium, tissue that lines the cervix, and accompanying levels of cytokines and chemokines in order to show basic biological differences in immune function of the cervix between adults and adolescents to account for the predominance of STIs in younger women.
Thirty-two women aged 13-21 were selected. The women were placed in the immature group (>50% columnar epithelium) or mature cervical group (<5% columnar epithelium). In order to help you envision these epithelial cells, think of a single line of figure skaters (fragile, columnar cells) versus a stack of sumo wrestlers (strong, squamous cells). Younger women have more columnar cells and throughout development the columnar cells become squamous cells. This is why it is extremely important to take variation into account, because at any given point in a woman’s development the ratio of squamous to columnar cells varies.
Participants were excluded for pregnancy, surgery on the cervix, cervical dysplasia (grades above 1), taking immunosuppressive agents, or being symptomatic for genital complaints such as yeast. However, women were not excluded for having HPV because the researchers consider it a very common infection. The women filled out surveys detailing sexual and nonsexual behavior (number of partners, contraception, substance abuse, etc) and reproductive health history (previous pregnancies, menarche, etc). Colpophotagraphs were taken of the cervical epithelium and the researchers measured and rated maturity by counting pixels from the photograph. Women were evaluated only once, a strong drawback to this study as they are interested in the variation of the epithelium.
They found that ten of the cytokines and chemokine levels were higher in the immature group (one cytokine was excluded). Although other studies have previously looked at cervical levels of cytokines and chemokines, this study looked at levels of these cell-signaling protein molecules in relation to type of cervical epithelium. The authors note that having more columnar cells may be considered beneficial for young women as these cells are more easily damaged and likely to initiate an immune response, but this would mean that younger women are less prone toward infection. The researchers then go on to conclude that because these columnar cells are more prone to damage and thus immune response, chronic inflammation is more likely which could lead to greater rates of infection. This study only looked at the epithelium of healthy women, so it is important to examine women with various infections in the future. The epithelium and levels of cytokines/chemokines in women with STIs could lead to a better understanding or correlation between type of epithelium and its subsequent immune response and risk rate.
In our discussion of the article, it was mentioned that there are no “normal” levels of cytokine and chemokine levels with which to compare the researcher’s values. In the study this was referred to as a challenge. Perhaps there will never be established normative levels of these protein molecules, but so what? Our lab group concluded that this should not be considered a challenge and may be beneficial as we will simply have to take variation into account which is strongly lacking in the medical realm of reproductive health! We all agreed that this study should have been conducted over a longer period of time, and that the women should have had their epithelium photographed and correlating levels of cytokines/chemokines measured far more often. Because this study’s main focus was variation of the epithilium, it would make sense for these women to contribute visits over the course of their entire menstrual cycle whereas this study simply adjusted for days since last menstrual cycle. We also discussed that this study may be perceived as far more qualitative than quantitative. However, we acknowledged that the clarity of the cervical photos was great so quantitative measurements of the pixels could be taken seriously. It was also noted that these findings were not all that surprising. It seems commonsense that younger women have cells that are more easily damaged and that this could lead to chronic inflammation that poses negative risks. Although this may be true, I think that we should still applaud these authors for acknowledging variation throughout their research.
I also find it interesting that the most common cervical cancer is squamous cell carcinoma. Columnar cells may be damaged more easily, but it seems that squamous cells are more prone towards division and supporting abnormal growth. Most cases of cervical cancer are due in part to HPV infection, which in going along with the findings of this article, is more common in younger women with immature columnar cells. It would be interesting to see how the squamous cells in women with cervical cancer compare to the columnar cells of women with HPV. Perhaps cervical cancer, as a result of HPV, is more common in women who have more columnar cells than squamous cells, but the cancer arises in and prefers the squamous cells because they are less likely to initiate a strong immune response. In general, I appreciate how easy and enjoyable this article is to read. Hopefully more articles acknowledging variation, particularly when it comes to reproductive health, will be published as a result of this interesting finding.
Reference
Hwang LY, Scott ME, Ma Y, & Moscicki AB (2011). Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium. Journal of reproductive immunology, 88 (1), 66-71 PMID: 21051089
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