Young women aged 15–24 years have the highest rates of sexually transmitted infections (STIs). The vulnerability of adolescents is often attributed to risky sexual behaviors, whereas biological factors affecting mucosal immunity are poorly understood. The objective of this cross-sectional study was to examine associations between the type of cervical epithelium and protein levels of 11 cervicovaginal cytokines and chemokines in non-pregnant healthy young women. Cervical epithelial types were viewed on colpophotography and measured quantitatively using computerized planimetry. We selected 16 women with immature epithelium (predominantly columnar and early/mid squamous metaplasia), and 16 women with mature epithelium (predominantly squamous epithelium). Cytokine levels were measured in cervicovaginal lavage samples by MILLIPLEX™ MAP Human Cytokine/Chemokine multiplex immunoassay. Bivariate Box-Cox regression models compared cytokine levels between immature and mature groups. Multivariate Box-Cox models adjusted separately for age, years since menarche, days since last menses, years of sexual activity, number of lifetime sexual partners, HPV infection, hormonal contraceptive use, smoking, bacterial vaginosis by Nugent’s criteria, and polymorphonuclear cells on wet prep. The mean age was 19.2 years. Women with immature epithelium demonstrated significantly higher levels of IL-1α, IL-1β, IL-6, IL-8, MIP-1α, RANTES, TNFα, IL-10, IL-12 and IFNγ (each p<0.01), compared to women with mature epithelium. Results remained highly significant in the multivariate models. Cytokine profiles in the healthy state may foreshadow differential responses to pathogens. Cervical epithelial type should be measured in clinical studies involving cervicovaginal immune markers.

Purpose To examine the longitudinal changes in the epithelial topography of the cervix in healthy young women; and to determine the sociodemographic, behavioral, and biological factors associated with the rate of cervical epithelial maturation. Methods Healthy young women were enrolled (10/00-9/02) as part of a larger study of human papillomavirus (HPV). At interval visits, interviews, infection testing, and colpophotography (3% acetic acid; 10X,16X magnifications) were performed. Areas of total cervical face and cervical immaturity, defined as columnar and early squamous metaplasia, were quantitatively measured using computerized planimetry. Cervical immaturity was expressed as percentage of total cervical face. This analysis includes the first consecutive 145 women with greater than 10% immaturity at baseline. The rate of cervical maturation was defined as change in percent-immaturity. Predictors included sociodemographics, sexual behaviors, and infections. Data analyses included multivariate generalized linear models with repeated measures. Results The baseline mean age was 17.8 years. Colpophotographs were available from 815 total visits, representing 2.7 years mean follow-up per woman and 5.9 month mean intervals. Women began the study with a median of 39% immaturity and ended with 8% immaturity. After adjusting for time and baseline percent-immaturity, an increased rate of cervical maturation was associated with oral contraceptive pill use (parameter estimate −0.023, p=0.04) and smoking (−0.039, p=0.01). Conclusions Cervical maturation was documented during relatively short time periods for the vast majority of these women. Oral contraceptive pills and smoking may accelerate the maturational process, representing increased cell proliferation and thus a possible greater vulnerability to HPV.

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This study sought to establish the feasibility of using in situ depth-resolved nuclear morphology measurements for detection of cervical dysplasia. Forty (40) enrolled patients received routine cervical colposcopy with angle-resolved low coherence interferometry (a/LCI) measurements of nuclear morphology. a/LCI scans from 63 tissue sites were compared to histopathological analysis of co-registered biopsy specimens which were classified as benign, low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL). Results were dichotomized as dysplastic (LSIL/HSIL) versus non-dysplastic and HSIL versus LSIL/benign to determine both accuracy and potential clinical utility of a/LCI nuclear morphology measurements. Analysis of a/LCI data was conducted using both traditional Mie theory based processing and a new hybrid algorithm that provides improved processing speed to ascertain the feasibility of real-time measurements. Analysis of depth-resolved nuclear morphology data revealed a/LCI was able to detect a significant increase in the nuclear diameter at the depth bin containing the basal layer of the epithelium for dysplastic versus non-dysplastic and HSIL versus LSIL/Benign biopsy sites (both p < 0.001). Both processing techniques resulted in high sensitivity and specificity (> 0.80) in identifying dysplastic biopsies and HSIL. The hybrid algorithm demonstrated a threefold decrease in processing time at a slight cost in classification accuracy. The results demonstrate the feasibility of using a/LCI as an adjunctive clinical tool for detecting cervical dysplasia and guiding the identification of optimal biopsy sites. The faster speed from the hybrid algorithm offers a promising approach for real-time clinical analysis.

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