Abstract
High risk-human papillomaviruses (HPVs) are known carcinogens. Numerous reports have linked the steroid hormone estrogen, and the expression of estrogen receptors (ERs), to HPV-related cancers, although the exact nature of the interactions remains to be fully elucidated. Here we will focus on estrogen signaling and describe both pro and potentially anti-cancer effects of this hormone in HPV-positive cancers. This review will summarize: (1) cell culture-related evidence, (2) animal model evidence, and (3) clinical evidence demonstrating an interaction between estrogen and HPV-positive cancers. This comprehensive review provides insights into the potential relationship between estrogen and HPV. We suggest that estrogen may provide a potential therapeutic for HPV-related cancers, however additional studies are necessary.
Highlights
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States
The Lambert laboratory and collaborators have demonstrated that the expression of the estrogen receptor α and E7 expression are intrinsically linked to the development and persistence of HPV-related cervical dysplasia and cervical cancer [117,126,127,128,129,130]
While there could be numerous reasons why there are such discrepancies in the ratio of men:women affected by HPV+OPC, it is in an interesting premise that pre-menopausal women have much higher circulating estrogen levels [69]
Summary
Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Numerous studies over the years have related estrogen and the expression of its receptors (ERα, ERβ) to HPV infections and to HPV-associated cancers. While productive viral infections rely on the expression of HPV in its episomal form, integration events can occur; these events are known to confer cellular growth advantages, and are thought to be a hallmark of cervical cancer progression [54,55,56]. The gene coding for GPER1 is found on chromosome 7 [69,87,88] This receptor does not share similarities with the nuclear receptors and is instead a typical G-protein coupled receptor (GPCR) which has been linked to rapid responses to estrogen through activation of intercellular signaling cascades through secondary messengers [69,82]. Mechanisms involving estrogen-receptor complex signaling are vast, appear to be cell type specific, and can interact with various pathways including ras, Src and PI3 kinases, EGFR, IGF1, AP-1, STATs, ATF-2/c-Jun, Sp1, NF-κB, CREB, Elk-1, and many others [95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
