Endogenous oestradiol and progesterone as predictors of oncogenic human papillomavirus (HPV) persistence

Abstract

Background High-risk human papillomavirus (HR-HPV) is the main aetiological factor for the development of cervical cancer. While nearly 70% of HR-HPV infections are cleared within 12 months, in the remainder of women they persist and can progress into cervical cancer. Oestradiol and progesterone have been shown to be involved in the development and progression of cervical cancer. The objective of this study was to investigate, for the first time, whether diurnal oestradiol and progesterone are also involved in HR-HPV persistence – before cervical cancer develops. Methods A total of N = 39 women between 18 and 31 years of age were investigated. All were nulliparous and regular users of combined oral contraceptives. Presence of HR-HPV was determined by cervical swabs. Salivary oestradiol and progesterone were measured upon awakening and at 11 am, 2 pm, and 5 pm. All HR-HPV positive women were re-tested in terms of HR-HPV status 12 months later. Results HR-HPV positive women had significantly higher morning (p = .007, partial eta2 = .221) and daily oestradiol levels (p < .001, partial eta2 = .442) when compared to HR-HPV negative women. In addition, those with persistent HR-HPV 12 months later had significantly elevated morning (p = .005, partial eta2 = .534) and daily (p = .027, partial eta2 = .346) oestradiol. Progesterone was found to be unrelated to HR-HPV. Conclusions Oestradiol was positively linked to HR-HPV presence and persistence. Provided that these findings are replicated, regular monitoring of oestradiol levels may prove useful in identifying women who are at risk of developing cervical cancer.

Stress keratin 17 and estrogen support viral persistence and modulate the immune environment during cervicovaginal murine papillomavirus infection

“…While the estrogen dose administered in our study has been shown to induce conditions consistent with persistent estrus in mice ( 54 ) models that rely upon endogenous physiological estrogen levels warrant investigation in our studies. Epidemiological studies have identified associations between several conditions that elevate estradiol levels in humans with increased risk for HPV persistence and subsequent neoplastic progression in the female reproductive tract, such as long-term oral contraceptive use, pregnancy, and multiparity ( 75 , 116 – 122 ). Given that estradiol levels also increase during the murine gestational period ( 123 ), future studies could explore the effect of pregnancy and/or multiparity on MmuPV1 viral persistence, clearance, and malignant progression under conditions where estrogen levels are naturally increased as opposed to exogenous treatment.…”

HPV-associated vulvar carcinoma with sebaceous differentiation

“…Studies in HPV-16 positive cell lines CaSki and SiHa demonstrated that estrogen increased proliferation of SiHa cells and appeared to protect CaSki cells from apoptosis ( Ruutu et al, 2006 ). In human studies, it has been demonstrated that HR-HPV positive women had significantly higher morning and daily estradiol levels compared to HR-HPV negative women ( Fischer et al, 2022 ). Estrogen receptors (ER) have been identified in epidermal keratinocytes and dermal fibroblasts of the vulva, which opens up the possibility that there may be an estrogen effect inducing oncogenic HPV activity on the vulva ( MacLean et al, 1990 ).…”