Estrogen and progesterone receptors in cervical human papillomavirus related lesions

Abstract

According to recent studies showing that human papillomavirus (HPV) infections can be influenced by sex steroid hormones, we performed estrogen (ER) and progesterone (PgR) receptor assays in fresh frozen biopsies of genital-HPV-related lesions. Seventy-three women with normal cervix, condyloma, low- and high-grade CIN and squamous carcinoma were evaluated in comparison with 15 persons with vulvar and 9 with penile papillomavirus-associated lesions. HPV genotypes were determined by dot-blot hybridization. Non-cervical lesions did not express HR. Condyloma on squamous metaplasia of the cervix and high-grade CIN expressed high levels of HR, particularly PgR (mean 4,086 and 4,518 fmoles/g tissue, respectively). Cervical squamous carcinoma expressed very low concentrations of PgR in a limited number of cases. High levels of PgR were correlated with high-grade CIN (p less than 0.05), HPV16-18-associated lesions (p less than 0.01) and ER were correlated to HPV6-11-related lesions (p less than 0.01). The levels were independent of age, cycle stage and oral contraception. Morphological localization of PgR, using an immunocytochemical method using a monoclonal antibody (MAb) (PR-ICA), showed intense homogeneous staining in the nuclei of the stromal fibroblasts underlying dysplastic epithelium and condyloma on squamous metaplasia. These results suggest that, under in vivo conditions, sex steroid hormones, particularly progesterone, may act indirectly on HPV-infected epithelial cells and be implicated as co-factors in HPV-related cervical neoplasia. They could explain the relative predisposition to malignant transformation of the cervix as compared with vulvar and penile mucosa.

Estrogen and progesterone receptors in human papilloma virus-related cervical neoplasia

“…This result is similar to that obtained in previous studies in which ER expression was found to be inversely associated with disease status (8,9,12). On the other hand, a similar ER distribution was observed in the stroma of both tumors and normal tissues.…”

“…For progesterone receptors (PR) the variation is even wider, i.e., 0 to 100% of tissues from the uterine cervix have been reported to be PR positive (8)(9)(10)(11)(12). No statistically significant correlations have been found for the ER/PR ratio in the cervix when related to menstrual cycle, menopause, histological type or ploidy analysis (8)(9)(10)(11).…”

“…One major explanation for these discrepancies could be related to the location of the receptors, which can be found either in the epithelium or in the stroma, to the size of the tissue analyzed, and to the method for receptor detection (8,9,13,14). In an attempt to clarify some of these issues we sought to evaluate the concentration of ER and PR in samples from the normal uterine cervix, from cervical intraepithelial neoplasia (CIN 1, 2 and 3) and from invasive carcinoma, associated or not with the presence of HPV DNA.…”

Role of hormone cofactors in the human papillomavirus-induced carcinogenesis of the uterine cervix

“…Although endometrial expression of estrogen and progesterone receptors has been shown to vary during the menstrual cycle (Fujishita et al, 1997;Ravn et al, 1994), no significant difference was demonstrated in hormone receptor-positive cell density between the follicular and luteal phases in both TZ and ectocervical biopsies (Remoue et al, 2003). These data are in agreement with previous studies showing no significant variation, within the menstrual cycle, in hormone receptor concentrations in vaginal tissues (Schwartz, 2000) and in HPV-associated lesions (Monsonego et al, 1991), suggesting a lower sensitivity to menstrual cycle changes of genital squamous mucosa compared to glandular endometrial tissues.…”

“…The expression of sex hormone receptors in human cervical biopsies has also been shown to be higher in the precancerous TZ compared to normal ectocervix and to increase with the grade of SIL, strengthening the hormone-dependent establishment of cervical (pre)neoplastic lesions (Monsonego et al, 1991).…”