The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers

James, Claire D.; Morgan, Iain M.; Bristol, Molly L.

doi:10.3390/pathogens9050403

Cited by 26 publications

(26 citation statements)

References 149 publications

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“…Recent studies in HPV transgenic mouse models provide evidence that estrogen and its nuclear receptor promote cervical cancer in combination with HPV (majorly HPV 16) oncogenes [ 97 ]. The steroid hormones modulate HPV gene transcription [ 98 , 99 ], and can therefore enhance the expression of viral oncogenes in persistent HR HPV infection in the settings of pregnancy, eventually leading to malignant transformation of the expressing cells, with associations between estrogen and HPV-positive cancers supported by clinical evidence [ 100 ]. Our finding of the association of the number of full-term pregnancies with HR HPV prevalence support the role of sex hormones in HPV persistence, translated into higher HR HPV detection rates, however, irrespective of HR HPV types ( Table 2 ), thus, was not explaining prevalence of certain HR HPV types (as WLWH positive for HPV 16 or for other HR HPVs did not differ in the number of pregnancies; Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and Risk Factors of Infection with High Risk Human Papilloma Viruses among HIV-Positive Women with Clinical Manifestations of Tuberculosis in a Middle-Income Country

et al. 2021

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Women living with HIV-1 are at high risk of infection with human papillomavirus of high carcinogenic risk (HR HPVs). M. tuberculosis (TB) promotes HPV infection and increases the risk to develop HPV-associated cancer. Our knowledge of persisting HR HPVs genotypes, and of the factors promoting HR HPV infection in people living with HIV-1 with clinical TB manifestations is sparse. Here, we analyzed 58 women living with HIV-1 with clinical TB manifestations (WLWH with TB) followed up in specialized centers in Russia, a middle income country endemic for HIV-1 and TB, for the presence in cervical smears of DNA of twelve HR HPV genotypes. DNA encoding HPV16 E5, E6/E7 was sequenced. Sociodemographic data of patients was collected by questionnaire. All women were at C2-C3 stages of HIV-infection (by CDC). The majority were over 30 years old, had secondary education, were unemployed, had sexual partners, experienced 2–3 pregnancies and at least one abortion, and were smokers. The most prevalent was HPV16 detected in the cervical smears of 38% of study participants. Altogether 34.5% of study participants were positive for HR HPV types other than HPV16; however, but none of these types was seen in more than 7% of tested samples. Altogether, 20.7% of study participants were positive for several HR HPV types. Infections with HPVs other than HPV16 were common among WLWH with generalized TB receiving combined ART/TB-therapy, and associated with their ability to work, indirectly reflecting both their health and lifestyle. The overall prevalence of HR HPVs was associated with sexual activity of women reflected by the number of pregnancies, and of HPV 16, with young age; none was associated to CD4+-counts, route of HIV-infection, duration of life with HIV, forms of TB-infection, or duration of ART, characterizing the immune status. Thus, WLWH with TB—especially young—were predisposed to infection with HPV16, advancing it as a basis for a therapeutic HPV vaccine. Phylogenetic analysis of HPV16 E5, E6/E7 DNA revealed no common ancestry; sequences were similar to those of the European and American HPV16 strains, indicating that HPV vaccine for WLWH could be the same as HPV16 vaccines developed for the general population. Sociodemographic and health correlates of HR HPV prevalence in WLWH deserve further analysis to develop criteria/recommendations for prophylactic catch-up and therapeutic HPV vaccination of this highly susceptible and vulnerable population group.

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Section: Discussionmentioning

confidence: 99%

Prevalence and Risk Factors of Infection with High Risk Human Papilloma Viruses among HIV-Positive Women with Clinical Manifestations of Tuberculosis in a Middle-Income Country

et al. 2021

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“…The absence of ER in the tumor epithelium however, doesn't preclude the tumor cells from utilizing estradiol available in the TME through the nongenomic pathway (reviewed in Somasundaram et al, 2020). These facts culminated in a recent review arguing out the pro and anti-tumorigenic actions of estradiol on the tumor epithelium in HPV-mediated malignancies (James et al, 2020). However, a tumor comprises of more than just mere malignant cells.…”

Section: Estrogen Signaling Pathways In Hpv Infected Squamous Epithelial Cellsmentioning

confidence: 99%

The Immune Microenvironment in Human Papilloma Virus-Induced Cervical Lesions—Evidence for Estrogen as an Immunomodulator

Jayshree

2021

Front. Cell. Infect. Microbiol.

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Globally, human papilloma virus (HPV) infection is a common sexually transmitted disease. However, most of the HPV infections eventually resolve aided by the body’s efficient cell-mediated immune responses. In the vast majority of the small group of patients who develop overt disease too, it is the immune response that culminates in regression of lesions. It is therefore a rarity that persistent infection by high-risk genotypes of HPV compounded by other risk factors progresses through precancer (various grades of cervical intraepithelial neoplasia—CIN) to cervical cancer (CxCa). Hence, although CxCa is a rare culmination of HPV infection, the latter is nevertheless causally linked to >90% of cancer. The three ‘Es’ of cancer immunoediting viz. elimination, equilibrium, and escape come into vogue during the gradual evolution of CIN 1 to CxCa. Both cell-intrinsic and extrinsic mechanisms operate to eliminate virally infected cells: cell-extrinsic players are anti-tumor/antiviral effectors like Th1 subset of CD4+ T cells, CD8+ cytotoxic T cells, Natural Killer cells, etc. and pro-tumorigenic/immunosuppressive cells like regulatory T cells (Tregs), Myeloid-Derived Suppressor Cells (MDSCs), type 2 macrophages, etc. And accordingly, when immunosuppressive cells overpower the effectors e.g., in high-grade lesions like CIN 2 or 3, the scale is tilted towards immune escape and the disease progresses to cancer. Estradiol has long been considered as a co-factor in cervical carcinogenesis. In addition to the gonads, the Peyer’s patches in the gut synthesize estradiol. Over and above local production of the hormone in the tissues, estradiol metabolism by the gut microbiome: estrobolome versus tryptophan non-metabolizing microbiome, regulates free estradiol levels in the intestine and extraintestinal mucosal sites. Elevated tissue levels of the hormone serve more than one purpose: besides a direct growth-promoting action on cervical epithelial cells, estradiol acting genomically via Estrogen Receptor-α also boosts the function of the stromal and infiltrating immunosuppressive cells viz. Tregs, MDSCs, and carcinoma-associated fibroblasts. Hence as a corollary, therapeutic repurposing of Selective Estrogen Receptor Disruptors or aromatase inhibitors could be useful for modulating immune function in cervical precancer/cancer. The immunomodulatory role of estradiol in HPV-mediated cervical lesions is reviewed.

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“…High-risk human papillomaviruses (HPVs) are the major carcinogens for cervical cancer and are responsible for most of this disease [ 126 ]. However, ER signaling is associated with HPV infection and cervical cancer in many aspects, including pro-carcinogenic and anti-carcinogenic relationship [ 127 ]. Recent study found that SRC-3 was more frequently high expressed in cervical cancer (52.7%) compared to normal cervical tissues (30%), and high level of SRC-3 is significantly associated with aggressiveness and chemoradiotherapy resistance [ 47 ].…”

Section: Implication Of Src-3 In Cancermentioning

confidence: 99%

SRC-3, a Steroid Receptor Coactivator: Implication in Cancer

Li¹,

Deng²,

Chen³

2021

IJMS

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Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer. This review updates the important progress of SRC-3 in carcinogenesis and summarizes its mode of action, which provides clues for cancer therapy.

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The Relationship between Estrogen-Related Signaling and Human Papillomavirus Positive Cancers

Cited by 26 publications

References 149 publications

Prevalence and Risk Factors of Infection with High Risk Human Papilloma Viruses among HIV-Positive Women with Clinical Manifestations of Tuberculosis in a Middle-Income Country

Prevalence and Risk Factors of Infection with High Risk Human Papilloma Viruses among HIV-Positive Women with Clinical Manifestations of Tuberculosis in a Middle-Income Country

The Immune Microenvironment in Human Papilloma Virus-Induced Cervical Lesions—Evidence for Estrogen as an Immunomodulator

SRC-3, a Steroid Receptor Coactivator: Implication in Cancer

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