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One of the crucial aspects of cancer research is diagnosis with specificity and accuracy. Early cancer detection mostly helps make appropriate decisions regarding treatment and metastasis. The well-studied transcription factor tumor suppressor protein p53 is essential for maintaining genetic integrity. p53 is a key tumor suppressor that recognizes the carcinogenic biological pathways and eradicates them by apoptosis. A wide range of carcinomas, especially gynecological such as ovarian, cervical, and endometrial cancers, frequently undergo TP53 gene mutations. This study evaluates the potential of the p53 gene as a biological marker for the diagnosis of reproductive system neoplasms. Immunohistochemistry of p53 is rapid, easy to accomplish, cost-effective, and preferred by pathologists as a surrogate for the analysis of TP53 mutation. Thus, this review lays a groundwork for future efforts to develop techniques using p53 for the early diagnosis of cancer.

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Aquaporin (AQP) channels in endometrial cancer (EC) cells are of interest as pharmacological targets to reduce tumor progression. A panel of compounds, including AQP1 ion channel inhibitors (AqB011 and 5-(phenoxymethyl) furan-2-carbaldehyde, PMFC), were used to test the hypothesis that inhibition of key AQPs can limit the invasiveness of low- and high-grade EC cells. We evaluated the effects on transwell migration in EC cell lines (Ishikawa, MFE-280) and primary EC cells established from surgical tissues (n = 8). Quantitative PCR uncovered classes of AQPs not previously reported in EC that are differentially regulated by hormonal signaling. With estradiol, Ishikawa showed increased AQPs 5, 11, 12, and decreased AQPs 0 and 4; MFE-280 showed increased AQPs 0, 1, 3, 4, 8, and decreased AQP11. Protein expression was confirmed by Western blot and immunocytochemistry. AQPs 1, 4, and 11 were colocalized with plasma membrane marker; AQP8 was intracellular in Ishikawa and not detectable in MFE-280. AQP1 ion channel inhibitors (AqB011; PMFC) reduced invasiveness of EC cell lines in transwell chamber and spheroid dispersal assays. In Ishikawa cells, transwell invasiveness was reduced ~41% by 80 µM AqB011 and ~55% by 0.5 mM 5-PMFC. In MFE-280, 5-PMFC inhibited invasion by ~77%. In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective. Treatments of cultured primary EC cells with AqB011 or PMFC significantly reduced the invasiveness of both low- and high-grade primary EC cells in transwell chambers. We confirmed the tumors expressed moderate to high levels of AQP1 detected by immunohistochemistry, whereas expression levels of AQP4, AQP8, and AQP11 were substantially lower. The anti-invasive potency of AqB011 treatment for EC tumor tissues showed a positive linear correlation with AQP1 expression levels. In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes.

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OBJECTIVE: To synthesize and examine current literature on survivorship experiences and psychosocial oncologic care programs of individuals affected by cancer in sub-Saharan Africa (SSA). METHODS: This was a systematic review guided by the PRISMA 2020 guidelines. We searched 6 databases for articles published from inception to 21 October 2021. Articles were appraised using the Johanna Briggs Institute's Checklist for Qualitative Research. For data synthesis, we used the World Health Organization (WHO) quality of life framework [WHOQOL] to organize experiences into 6 domains/themes. RESULTS: Twenty-five qualitative studies were included in the synthesis. Studies focused on psychosocial care of adults (>18 years) affected by cancer in SSA. The common WHOQOL domains were social relations, spirituality/religion/personal beliefs, and psychological. CONCLUSION: Findings echo need for individuals with cancer and their caregivers. Healthcare professionals are an essential resource for information and support services that can be tailored to individuals need. This synthesis highlighted caregiver stress and stressors from the community that could impact care of individuals with cancer. A holistic approach is needed that incorporates professional and social aspects of care.

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Genomic instability and genetic mutations can lead to exhibition of several cancer hallmarks in affected cells such as sustained proliferative signaling, evasion of growth suppression, activated invasion, deregulation of cellular energetics, and avoidance of immune destruction. Similar biological changes have been observed to be a result of pathogenic viruses and, in some cases, have been linked to virus-induced cancers. Human endogenous retroviruses (HERVs), once external pathogens, now occupy more than 8% of the human genome, representing the merge of genomic and external factors. In this review, we outline all reported effects of HERVs on cancer development and discuss the HERV targets most suitable for cancer treatments as well as ongoing clinical trials for HERV-targeting drugs. We reviewed all currently available reports of the effects of HERVs on human cancers including solid tumors, lymphomas, and leukemias. Our review highlights the central roles of HERV genes, such as gag, env, pol, np9, and rec in immune regulation, checkpoint blockade, cell differentiation, cell fusion, proliferation, metastasis, and cell transformation. In addition, we summarize the involvement of HERV long terminal repeat (LTR) regions in transcriptional regulation, creation of fusion proteins, expression of long non-coding RNAs (lncRNAs), and promotion of genome instability through recombination.

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Although cholesterol has been hypothesized to promote cancer development through several potential pathways, its role in the risk of developing hormonally driven cancer is controversial. This literature review summarizes evidence from the highest quality studies to examine the consistency and strength of the relationship between serum cholesterol parameters and incidence of hormonally driven cancer. Articles were identified using EMBASE. Longitudinal observational studies published between January 2000 and December 2020 were considered for inclusion. The endpoint of interest was incident prostate, ovary, breast, endometrium, and uterine cancers. In total, 2732 reports were identified and screened; 41 studies were included in the review. No associations were found for ovarian cancer. Most endometrial cancer studies were null. The majority (76.9%) of studies reported no association between cholesterol and prostate cancer. Data on breast cancer were conflicting, associations limited, and effect sizes modest. Our results do not provide evidence for a clear association between cholesterol and different types of incident, hormonally driven reproductive cancers. Future studies should investigate the impact of lipid-lowering therapy.

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Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or anti-metastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers.

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In recent years, the incidence of the reproductive diseases is increasing year-by-year, leading to abortion or fetal arrest, which seriously affects the reproductive health of human beings and the reproductive efficiency of animals. Exosomes are phospholipid bilayer vesicles that are widely distributed in living organisms and released by the cells of various organs and tissues. Exosomes contain proteins, RNA, lipids, and other components and are important carriers of information transfer between cells, which play a variety of physiological and pathological regulatory functions. More and more studies have found that exosomes and their connotations play an important role in the diagnosis, prognosis and treatment of diseases. A systematic review was conducted in this manuscript and then highlights our knowledge about the diagnostic and therapeutic applications of exosomes to reproductive diseases, such as polycystic ovary syndrome (PCOS), endometriosis, premature ovarian failure (POF), preeclampsia, polycystic, endometrial cancer, cervical cancer, ovarian cancer, and prostate gland cancer.

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South Africa is currently undergoing epidemiological and health transition that may impact on the risk factors of endometrial cancer mortality. We evaluated the sociodemographic characteristics of women that died from endometrial cancer in South Africa from 1997 to 2015.An unmatched case control study was conducted to compare the sociodemographic characteristic of women that died from endometrial cancer cases (n = 3,955) with the characteristics of women that died from other cancers (controls, n = 66,202) using the population-based mortality data from Statistics South Africa. Unconditional binary logistic regression modelling was conducted.The Mean age of women that died from endometrial cancer was 66.7 ± 11.9 years. The odds of death from endometrial cancer among women aged ≥50 years was about 4-fold as compared to women younger than 50 years (AOR = 3.98 95% CI: 3.14 - 5.03; p value: <.001). Conversely, high school leavers (AOR = 0.79 95% CI: 0.66 - 0.94; p value: .009), smokers (AOR= 0.53 95% CI: 0.43 - 0.65; p value: <.001), and divorced women (AOR= 0.73 95% CI: 0.59 - 0.89; p value: .002) had lesser odds of endometrial cancer mortality.This study provides information to guide Public Health control program on endometrial cancer in South Africa.Impact statementWhat is already known on this subject? The prevalence of endometrial cancer is increasing in low and middle income countries. After the abolition of Apartheid in South Africa, the country commenced a multi-racial government that provided socio-economic empowerment to the majority of the country. Thus, South Africa is currently undergoing epidemiological and health transition that may impact on the risks of endometrial cancer in the country.What do the result of the study add? This study is the first in South Africa to evaluate the sociodemographic characteristics of women that died from endometrial cancer using a large population-based data. Age, educational status, smoking status are some identified risk factors of mortality from endometrial cancer in South AfricaWhat are the implications of these findings for clinical practice and/or further research? The highlighted risk factors that are associated with endometrial mortality will help in guiding health policies that will help reduce the prevalence of endometrial cancer. The study recommends a targeted national prevention program for endometrial cancer as the burden appears to be worsening with each passing year.

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Background: Men with non-reproductive cancers have a discrepant outcome compared to women. However, they differ significantly in the incidence of cancer type and characteristics. Methods: Patients with single primary cancer who were 18 years or older and whose data were gathered and made accessible by the Surveillance, Epidemiology, and End Results (SEER) program were included in this retrospective analysis. Kaplan-Meier curves and Cox regression before and after propensity score matching were performed to analyze the risk survival by sex. Results: Among the 1,274,118 patients included [median (range) age, 65 year (18-85+) years; 688,481 (54.9%) male]. The median follow-up was 21 months (0-191). Substantial improvements in survival were observed for both sexes during the years of inclusion analyzed, with no difference between them, reaching a reduction of almost 17% of deaths in 2010, and of almost 28% in 2015, compared to 2004. The women had a median survival of 74 months and overall mortality of 48.7%. Males had a median survival of 30 months (29.67-30.33) with an overall mortality of 56.2%. The PSM showed a reduced difference (6 months shorter median survival and 2.3% more death in men), but no change in hazards was observed compared to the unmatched analysis [adjusted HR: 0.888 (0.864-0.912) vs. 0.876 (0.866-0.886) in unmatched]. Conclusions: The discrepancy in survival between men and women is not explained only by the incidence of more aggressive and more advanced cancers in the former.

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Aquaporins are membrane channels in the broad family of major intrinsic proteins (MIPs), with 13 classes showing tissue-specific distributions in humans. As key physiological modulators of water and solute homeostasis, mutations, and dysfunctions involving aquaporins have been associated with pathologies in all major organs. Increases in aquaporin expression are associated with greater severity of many cancers, particularly in augmenting motility and invasiveness for example in colon cancers and glioblastoma. However, potential roles of altered aquaporin (AQP) function in reproductive cancers have been understudied to date. Published work reviewed here shows distinct classes aquaporin have differential roles in mediating cancer metastasis, angiogenesis, and resistance to apoptosis. Known mechanisms of action of AQPs in other tissues are proving relevant to understanding reproductive cancers. Emerging patterns show AQPs 1, 3, and 5 in particular are highly expressed in breast, endometrial, and ovarian cancers, consistent with their gene regulation by estrogen response elements, and AQPs 3 and 9 in particular are linked with prostate cancer. Continuing work is defining avenues for pharmacological targeting of aquaporins as potential therapies to reduce female and male reproductive cancer cell growth and invasiveness.

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OBJECTIVES: Paired box protein-8 (PAX-8) immunohistochemical expression can be used as a diagnostic marker for epithelial cells tumors. This study aimed at investigating the immunohistochemical expression of PAX-8 among Sudanese females diagnosed with cervical, endometrial, and ovarian cancers between December 2017 and May 2019 by studying their Formalin-fixed paraffin embedded blocks. RESULTS: Sixty patients diagnosed with female reproductive tract cancers were included who aged 58.7 ± 6.9 years (range, 43-71). Cervix was the most common cancer site in 51/60 (85%) patients. Regarding cancer stage, there was 17 (28%) and 14 (23%) of the study population had stage 3B and 2B, respectively. The histopathological diagnosis included 20 (44%), 13 (29%), and 12 (27%) poorly, moderately, and well differentiated cervical squamous cell carcinoma (SCC) as well as 11 (73%), 2 (13%), 1 (7%), and 1 (7%) endometrial adenocarcinoma, metastatic adenocarcinoma, endocervical adenocarcinoma, and ovarian mucinous cyst adenocarcinoma, respectively. PAX-8 was positively expressed in 9 endometrial adenocarcinoma, 1 endocervical adenocarcinoma and 1 ovarian mucinous cyst adenocarcinoma, 2 poorly, and 1 moderately differentiated SCC. All patients diagnosed with well differentiated SCC and metastatic adenocarcinoma showed no expression of PAX-8. A statistically significant was seen for PAX-8 expression and the different histopathological diagnosis, P value < 0.001.

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BACKGROUND: The aim of this study was to evaluate the prevalence of some gynecological cancer risk factors in a population of female relatives of cancer patients in Hacettepe University Oncology Hospital. Additionally, what are the levels of the women's awareness /behavior toward available screening tools? METHODS: An individual cancer risk assessment questionnaire has been developed in the Department of Preventive Oncology, which questions the medical history, health behaviors and cancer awareness, as well as their behavior toward available cancer screening tools. RESULTS: The mean age of the study population was 45.7 ± 12.2 years. Median age at menarche was 13 years (IQR, 12-14), 6.9% of the women reported their menarche was before age of 12. About 11.1% of the women had intercourse before age of 18. The median age at first delivery was 22 years. Median BMI was 24.9, with 18.3% of population having obesity. Of the women 65% were current/past smokers. Sixty-two percent of the women had never used condom. About 8% of the women were unaware about mammography and 17.7% about the Pap test. CONCLUSIONS: This study has documented high tobacco use, low protective condom use and low rates of physical activity. Percentage of some risk factors like early menarche was lower than what was suggested for general Turkish population. Awareness and behavior of the women were better about mammography when compared to the Pap test. Considering our results, some measures should be put in place to increase people's awareness, and to modify their behavior toward cancer prevention.

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Women diagnosed with gynaecological cancer may face unwanted loss of fertility as well as all the other life-changing issues with which cancer and its treatments are associated. The decision to harvest and store gametes has to be made before commencement of treatment, and advances in these techniques have made this successful. Fertility sparing therefore must be discussed and offered at an early stage post diagnosis. Surrogacy is currently an evidence-based method of assisted reproduction, with mainly desirable outcomes for the commissioning mother, surrogate and child, without impacting on the cancer treatment and long-term survival. Surrogacy is therefore ethical as long as the autonomous rights of both the commissioning mother and gestational carrier are equally observed, they both have equal legal protection and due attention is paid to the short- and long-term welfare of any resulting offspring.

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There is a dearth of existing research on the treatment of reproductive cancers among women with intellectual and developmental disabilities (IDD). This study analyzed the 2010 Healthcare Cost and Utilization Project Nationwide Inpatient Sample and compared the prevalence of reproductive cancer treatment hospitalization discharges among women with and without IDD. Discharges linked to women with IDD had higher incidences of cancer of the uterus and lower prevalence of cancer of the cervix. Moreover, discharges linked to women with IDD indicated these women were younger, had longer hospital stays, and were more likely to have public insurance coverage. Therefore, further research and targeted interventions to increase cancer prevention and screening are urgently needed.

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Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.

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BACKGROUND: This analysis provides the final results on cancer incidence in relation to oral contraceptive (OC) use from the Oxford-Family Planning Association (Oxford-FPA) contraceptive study, which closed at the end of 2010. An additional 6 years of observation have been added since our last report and there has been an increase in the numbers of cancers of over 50% at seven of the sites considered. STUDY DESIGN: The Oxford-FPA study includes 17032 women aged 25-39 years recruited from 1968 to 1974 at contraceptive clinics in England and Scotland. These women were using OCs, a diaphragm or an intrauterine device. Information about cancer incidence among them has been collected from recruitment until closure of the study. RESULTS: OC use was not related to nonreproductive cancer. Breast cancer findings (1087 cases) were entirely negative; the rate ratio (RR) comparing ever users of OCs with never users was 1.0 [95% confidence interval (CI): 0.9-1.1]. Only two cases of cervical cancer have been added since our last report (total: 61 cases); the RR comparing ever use with never use is now 3.4 (95% CI: 1.6-8.9). The risk of this disease increases sharply with duration of OC use and declines steadily with interval since last OC use. OC use protects against both uterine body cancer (124 cases) and ovarian cancer (143 cases). The RRs comparing ever use with never use were 0.5 (95% CI: 0.3-0.7) and 0.5 (95% CI: 0.4-0.7), respectively. Protection against both these cancers increased with duration of OC use and waned with interval since last use, but an effect was still present 28 or more years after discontinuation. CONCLUSIONS: In our study, OC use had no effect on nonreproductive cancers or on breast cancer. The risk of cervical cancer was increased and that of uterine body cancer and ovarian cancer was decreased by OC use. All these effects increased with duration of use and declined with interval since last use. The beneficial effects of OC use on cancer outweighed the adverse effects. These findings should reassure older women who used OCs in the past.

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