Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland,Australia

BackgroundIncreases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia.MethodsIncidence data for 1982–2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression.ResultsThe incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50–69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC.ConclusionsIncidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males.     

Breast cancer trends in women younger than 40 years in Brazil

BackgroundA recent Brazilian populational database analysis showed a concerning increase in breast cancer mortality rates among patients under 40 years. We aimed to evaluate the trends in the proportion of new breast cancer cases and deaths occurring in patients younger than 40 years over the last decade in Brazil.MethodsWe evaluated all consecutive breast cancer patients treated from 2009 to 2020 in a Brazilian tertiary cancer center. The proportions of new cases and deaths in patients younger than 40 years was compared between two time periods (2015–2020 versus 2009–2014) using Chi-squared test. Linear regression was used to evaluate the trends in the proportion of new cases and deaths in young patients over the years.ResultsFrom 2009 to 2020, a total of 12,569 breast cancer patients started treatment at our institution; 1441 were younger than 40 years. From 2009 to 2014, 9.9% (95% CI 9.2–10.7%) were patients younger than 40 years compared to 12.9% (95% CI 12.1–13.8%) from 2015 to 2020. Similarly, the proportion of deaths among breast cancer patients younger than 40 years increased during the period (2009–2014: 9.6%, 95% CI 7.8–11.6%; 2015–2020: 12.4%, 95% CI 10.9–14%). The linear regression model showed a trend for an increasing proportion of new breast cancer cases occurring in patients under 40 years (P = 0.005). Proportion increased from 7.9% (95% CI 6.2–9.8%) in 2009 to 21.8% (95% CI 19.1–24.8%) in 2020. The trend for the increase in the proportion of deaths in this young population was also observed in the linear regression model (P = 0.01).ConclusionsThe proportion of new breast cancer cases and deaths among patients younger than 40 years has increased in a public Brazilian cancer center over the past decade. These results raise the concern for the need to reconsider primary and secondary prevention strategies for young women.     

Clear differences in ovarian cancer incidence and trends by ethnicity among Asian Americans

BackgroundAcross major races in the United States (U.S.), ovarian cancer incidence is low among Asian American women. However, this observation aggregates Asian Americans as a single group despite their heterogeneity. Disaggregating the ethnic Asian population will produce more useful information to better understand ovarian cancer incidence among Asian women in the U.S.MethodsData from the Surveillance, Epidemiology, and End Results Program from 1990 to 2014 were used to compare age-adjusted incidence rates (AAIRs, per 100,000 women) for ovarian cancer for the six largest U.S. Asian ethnicities (Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese) to non-Hispanic whites (NHWs). The race/ethnicity-specific AAIRs were calculated by time period and histotype. We examined the magnitude and direction of AAIR trends using average annual percent change (AAPC) statistics.ResultsAll Asian ethnicities had significantly lower ovarian cancer incidence rates than NHWs. However, among Asian ethnicities, Asian Indians/Pakistanis had the highest rate of ovarian cancer (AAIR = 10.51, 95% CI: 9.65–11.42) while Koreans had the lowest (AAIR = 7.23, 95% CI: 6.62–7.88). Clear cell ovarian cancer had significantly higher incidence rates among Chinese, Filipino, and Japanese women than NHW women (incidence rate ratio (IRR) = 1.49, 95% CI: 1.29–1.72, IRR = 1.30, 95% CI: 1.12–1.51, IRR = 1.64, 95% CI: 1.36–1.97, respectively). Incidence trends also differed by Asian ethnicity with significant decreases only observed for Chinese (AAPC = −1.49, 95% CI: −2.22 to −0.74) and Japanese (AAPC = −1.75, 95% CI: −2.57 to −0.92).ConclusionsExamining Asian Americans as a single group results in missed ethnic-specific disparities in ovarian cancer, hence disaggregating this heterogeneous population in future research is warranted.     

The impact of skin cancer prevention efforts in New South Wales,Australia: Generational trends in melanoma incidence and mortality

BackgroundIn Australia, skin cancer awareness campaigns have focused on raising the awareness and consequences of skin cancer and highlighting the importance of utilising sun protection.MethodsTrends in melanoma incidence and mortality have been explored elsewhere in Australia and this study sought to examine the trends in NSW. Anonymised incidence and mortality data for in situ and invasive melanoma from 1988 to 2014 were obtained from the NSW Cancer Registry. Trends of melanoma incidence and mortality were analysed using segmented regression to allow for changes over time. Birth cohort patterns were assessed using age–period–cohort models.ResultsOver the period, incidence of in situ melanoma increased in all age groups although the rates were lowest in those under 40 years of age. Incidence of invasive melanoma was either stable or decreased in people under 60, while it increased in those aged 60 and above, particularly in men. Age–period–cohort analysis revealed decreasing age-specific incidence of invasive melanoma under 40 years of age. Melanoma mortality over the period was stable or decreased in all groups except in men aged 60 or over. Overall, mortality rates generally declined or remained stable particularly in recent years.ConclusionIt is encouraging that rates of invasive melanoma are declining in the younger age cohorts – which could be attributed to both primary prevention efforts with individuals protecting their skin as well as early detection through self assessment and clinician performed skin checks. In addition, whilst it is important to monitor the increasing rates of in situ melanoma, the increase is likely due to early detection and treatment of melanoma that could have progressed to invasive melanoma and therefore detection whilst still in situ is an improved outcome. Overall, the results demonstrate the need to continue to improve the understanding of and compliance with primary skin cancer prevention measures in order to reduce population UVR exposure and overall melanoma incidence.     

Polymorphisms of estrogen receptor alpha gene in endometrial cancer

It is hypothesized that polymorphisms of estrogen receptor-alpha (ERalpha) gene are involved in endometrial cancer. To test this hypothesis, the genotype distributions of six different loci (codon 10 T-->C, codon 87 G-->C, codon 243 C-->T, codon 325 C-->G, codon 594 G-->A, and intron 1 C-->G) of the ERalpha gene were investigated and their association with endometrial cancer was determined. The DNA from 113 cases of human endometrial cancer was analyzed by sequence-specific polymerase chain reaction. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. The frequency of variant genotype on codon 10 was significantly lower in endometrial cancer patients as compared to controls. Nine of 113 endometrial cancer patients (8.0%) showed genotype 10C/C compared to 27 of 200 healthy controls (13.5%). The relative risk of genotype 10C/C was calculated as 0.44, compared to wild-type. Forty-five of 113 endometrial cancer patients (39.8%) showed genotype T/C on codon 10 compared to 111 of 200 healthy controls (55.5%). The relative risk of genotype 10T/C was calculated as 0.67, compared to wild-type. The polymorphism on codon 87 was not detected both in endometrial cancer patients and in healthy control. Other loci, intron 1, and codons 243, 325, and 594, did not show a correlation with endometrial cancer. The frequency of alleles on codon 10 was also significantly lower in endometrial cancer patients as compared to controls. Sixty-three of 226 alleles (27.9%) of endometrial cancer patients showed allele C compared to 165 of 400 (41.2%) of healthy controls. The relative risk of allele 10C was calculated as 0.67, compared to wild-type. Other loci, intron 1, and codons 243, 325, and 594, did not show a difference between cancer patients and controls. All genotype and allelic distributions were in accordance with the Hardy-Weinberg equilibrium. The present study demonstrates for the first time a protective effect of 10C allele against endometrial cancer. Thus, inherited alterations in ERalpha may be associated with changes in estrogen metabolism and thereby may possibly explain inter-individual differences in disease incidences of endometrial cancer.     

Male-origin microchimerism and endometrial cancer: A prospective case-cohort study

BackgroundMany women carry male cells of presumed fetal origin–so-called male-origin microchimerism (MOM)–in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer.MethodsWe designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50–64 years and cancer-free at enrolment in 1993–1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations.ResultsWe detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47–1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39–1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35–2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78–1.21).ConclusionsOur study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.     

c-Jun N-terminal kinase regulates apoptosis in endometrial cancer cells

c-Jun N-terminal kinases (JNKs) are important regulators of cell proliferation and apoptosis that have been implicated in tumorigenesis. We investigated the role of JNKs in apoptotic responses in Ishikawa and HEC-50 cells, models of type I and type II endometrial cancer, respectively. Etoposide treatment or UV irradiation resulted in sustained activation of JNK, correlating with the induction of apoptosis. Inhibition of JNK, or MAP kinase kinase 4 (MKK4), selectively suppressed apoptotic responses in both Ishikawa and HEC-50 cells. Knockdown of protein kinase C δ (PKCδ) also attenuated apoptosis in endometrial cancer cells and inhibited the sustained, UV-mediated JNK activation in HEC-50, but not Ishikawa cells. Etoposide-induced JNK phosphorylation was unaffected by PKCδ knockdown, implying that JNK can regulate apoptosis by PKCδ-dependent and independent pathways, according to stimulus and cell type. Thus, expression and activity of JNK and PKCδ in endometrial cancer cells modulate apoptosis and sensitivity to chemotherapeutic agents and may function as tumor suppressors in the endometrium. Elaine M. Reno and James M. Haughian are first authors.     

Hormones and cancer in humans

Hormones play a major role in the aetiology of several of the commonest cancers worldwide, including cancers of the endometrium, breast and ovary in women and cancer of the prostate in men. It is likely that the main mechanisms by which hormones affect cancer risk are by controlling the rate of cell division, the differentiation of cells and the number of susceptible cells. Hormones have very marked effects on cell division in the endometrium; oestrogens stimulate mitosis whereas progestins oppose this effect. The risk for endometrial cancer increases with late menopause, oestrogen replacement therapy and obesity, and decreases with parity and oral contraceptive use; thus risk increases in proportion to the duration of exposure to oestrogens unopposed by progestins, probably because unopposed oestrogens stimulate endometrial cell division. The effects of hormones on breast epithelial cell division in non-pregnant women are much less clear-cut than their effects on the endometrium, but both oestrogens and progestins appear to stimulate mitosis. Breast cancer risk increases with early menarche, late menopause and oestrogen replacement therapy, probably due to increased exposure of the breasts to oestrogen and/or progesterone. Early first pregnancy and multiparity reduce the risk for breast cancer, probably due to the hormonally-induced differentiation of breast cells and the corresponding reduction in the number of susceptible cells. Hormones do not have marked direct effects on the epithelial cells covering the ovaries, but hormones stimulate ovulation which is followed by cell division during repair of the epithelium. Risk for ovarian cancer increases with late menopause and decreases with parity and oral contraceptive use, suggesting that the lifetime number of ovulations may be a determinant of risk. For all three of these cancers risk changes within a few years of changes in exposure to sex hormones and some of the changes in risk persist for many years, indicating that hormones can affect both early and late stages of carcinogenesis. Understanding of the role of sex hormones in the aetiology of prostate cancer and of some rarer cancers is less complete.     

Calcium and calcium-related proteins in endometrial cancer: opportunities for pharmacological intervention

Intracellular calcium ions are key second messengers and play an important role in malignant transformation and cancer progression. Estrogen can evoke intracellular calcium increases through membrane-initiated effects and activate subsequent kinase cascades within minutes in normal and cancerous epithelial cells. Ca²⁺-related proteins are expressed in normal epithelial cells or endometrial cancer cells, some of which are upregulated by estrogen. Both estrogen-induced transient calcium increases and long-term changes in protein expression levels may be involved in regulating cancer initiation, progression and metastasis. Calcium channel blockers are reported to regulate both the rapid estrogen-induced intracellular Ca²⁺ increase and cell proliferation, apoptosis and migration, thus having the potential for pharmacological modulators to be repurposed for the treatment of endometrial cancer.     

Subsite- and stage-specific colorectal cancer trends in Estonia prior to implementation of screening

BackgroundThe occurrence of colorectal cancer (CRC) in Estonia has been characterised by increasing incidence, low survival and no screening. The study aimed to examine long-term incidence and survival trends of CRC in Estonia with specific focus on subsite and stage.MethodsWe analysed CRC incidence and relative survival using Estonian Cancer Registry data on all cases of colorectal cancer (ICD-10 C18–21) diagnosed in 1995–2014. TNM classification was used to categorise stage.ResultsAge-standardized incidence of colon cancer increased both in men and women at a rate of approximately 1% per year. Significant increase was seen for right-sided tumours, but not for left-sided tumours. Rectal cancer incidence increased significantly only in men and anal cancer incidence only in women. Age-standardized five-year relative survival for colon cancer increased from 50% in 1995–1999 to 59% in 2010–2014; for rectal cancer, from 38% to 56%. Colon cancer survival improved significantly for left-sided tumours (from 51% to 62%) and stage IV disease (from 6% to 15%). For rectal cancer, significant survival gain was seen for stage II (from 58% to 75%), stage III (from 34% to 70%) and stage IV (from 1% to 12%).ConclusionIn the pre-screening era in Estonia, increase in colon cancer incidence was limited to right-sided tumours. Large stage-specific survival gain, particularly for rectal cancer, was probably due to better staging and advances in multimodality treatment. Nonetheless, more than one quarter of new CRC cases are diagnosed at stage IV, emphasising the need for an efficient screening program.     

Repurposing of antipsychotics perphenazine for the treatment of endometrial cancer

Endometrial cancer (EC) is one of the most common and fatal gynecological cancers worldwide, but there is no effective treatment for the EC patients of progesterone resistance. Repurposing of existing drugs is a good strategy to discover new candidate drugs. In this text, perphenazine (PPZ), approved for psychosis therapy, was identified as a potential agent for the treatment of both progesterone sensitive and resistant endometrial cancer for the first time. Specifically, perphenazine exhibited good cell proliferation inhibition in Ishikawa (ISK) and KLE cell lines according to the CCK-8 assay and colony formation assay. It also reduced the cell migration of ISK and KLE cell lines in the light of the transwell migration assay. Annexin-V/PI double staining assay suggested that perphenazine could effectively induce ISK and KLE cell apoptosis. Moreover, results of western blot assay indicated perphenazine obviously inhibited the phosphorylation of Akt. Delightedly, PPZ also could significantly attenuate xenograft tumor growth at both 3 mg/kg and 15 mg/kg in mice without influencing the body weights.     

奥沙利铂对子宫内膜癌HEC-1A侵袭转移的影响

目的研究奥沙利铂对人子宫内膜癌细胞HEC-1A侵袭转移的影响。方法体外稳定培养HEC-1A细胞株系,用不同浓度奥沙利铂(40、80、160μg/ml)给药72h后,采用Transwell法测定奥沙利铂对HEC-1A侵袭能力的影响,重组基底膜试验测定奥沙利铂对HEC-1A粘附能力的影响,划痕试验检测奥沙利铂对HEC-1A迁移能力的影响。结果与未处理对照组比较,奥沙利铂(40、80、160μg/ml)明显抑制HEC-1A侵袭性,提高侵袭抑制率(P0.01),显著降低肿瘤细胞的迁移能力(P0.01),降低HEC-1A粘附程度(P0.01)。结论奥沙利铂有效抑制子宫内膜癌细胞继发性侵袭及转移,从而发挥抗癌作用。     

Regional trends of minimally invasive radical hysterectomy for cervical cancer and exploration of perioperative outcomes

IntroductionRadical hysterectomy (RH) with bilateral pelvic lymph node dissection is the standard treatment for early stage cervical cancer which can be performed either by an abdominal or a minimally invasive (MIS) approach. In 2018, Ramirez et al. presented their randomized-controlled trial data which demonstrated that patients who were treated with minimally invasive surgical (MIS) radical hysterectomy (RH) had higher rates of locoregional disease recurrence and lower rates of overall survival when compared to patients treated with an abdominal approach. The objective of this study is to examine the trends in management of patients diagnosed with cervical cancer in New York State (NYS) and to analyze their perioperative outcomes.MethodsUsing the Statewide Planning and Research Cooperative System (SPARCS) Database, patients undergoing RH for early stage cervical cancer in NYS between the years of 2007–2015 were identified and categorized based on surgical approach. Demographic information was collected and multivariable regression was conducted to assess the impact of hysterectomy approach on perioperative outcomes.ResultsIn NYS, 5575 patients were treated with RH for early stage cervical cancer with 3257 (58.4%) treated by abdominal RH and 2318 (41.6%) treated with MIS RH. Between the years of 2007 and 2015, patients diagnosed with cervical cancer treated with MIS RH increased from 25.7% to 48.3% respectively. Surgeons performing MIS RH were more likely to be younger (average age 47.1 vs 49.2, p < 0.001) and have less time elapsed from their fellowship graduation (20.37 vs 22.64 years, p < 0.001). Patients who saw high volume doctors (OR 1.95, CI 1.65–2.31) and were seen in high volume facilities (OR 1.40, CI 1.18–1.65) were more likely to undergo MIS RH compared to abdominal RH. Patients who underwent MIS RH were more likely to be discharged home as opposed to acute rehab or nursing facility, when compared to patients treated with abdominal RH (98.5 vs 94.2% p < 0.001). When analyzing perioperativce outcomes, patient undergoing MIS RH had a 85% decrease in length of hospital stay compared to abdominal RH, a 40% reduction in 30-day readmission rates, and a 10% reduction in hospital costs respectively.DiscussionIn our study period, between the years of 2007 and 2015, the number of cervical cancer cases treated with MIS RH increased from 25.7% to 48.3%. MIS techniques led to a reduction in length of hospital stay, patient readmission rates, and hospital costs. Based on recent data from Ramirez et al., preliminary data demonstrated decrease in MIS RH for treatment of cervical cancer after presentation of the LACC trial and our data confirmed these reported trends in NYS. With this change in surgical practice, there will be associated changes in perioperative outcomes. Moreover, for patients diagnosed with cervical cancer with microscopic disease or previous treatment with an excisions procedure, MIS approach should be considered for improvement in perioperative outcomes as long as oncologic outcomes are not compromised.     

Cryoablation used in fertility-sparing treatment for early endometrial cancer: A pig model experiment using a new designed balloon cryoprobe

Young patients with early endometrial cancer have a strong desire to retain reproductive function, which require us to develop a therapeutic method that can not only assure the complete resection of tumor but also retain the uterine integrity. In the present study, we proposed a fertility-sparing surgery option that combined hysteroscopic resection with cryoablation to achieve this goal. To verify the safety and effectiveness of cryoablation for local uterine wall, we designed the experiment in pig model using a novel cryoablation balloon probe. In the process of freezing and thawing, the temperature of different parts of the uterus was measured in real time. The uterus was harvested immediately, three weeks after cryotherapy for histological evaluation. The results demonstrated cryoablation using the new cryoprobe is safe and effective. The effective freezing range can cover a range of 2 cm in diameter at least. This study provided us evidence before cryoablation could be applied in clinical practice of fertility-sparing treatment for young women with early endometrial cancer.     

Defining a mutational signature for endometrial cancer screening and early detection

IntroductionThe current availability of genomic information represents an opportunity to develop new strategies for early detection of cancer. New molecular tests for endometrial cancer may improve performance and failure rates of histological aspirate-based diagnosis, and provide promising perspectives for a potential screening scenario. However, the selection of relevant biomarkers to develop efficient strategies can be a challenge.Materials and methodsWe developed an algorithm to identify the largest number of patients with endometrial cancer using the minimum number of somatic mutations based on The Cancer Genome Atlas (TCGA) dataset.ResultsThe algorithm provided the number of subjects with mutations (sensitivity) for a given number of biomarkers included in the signature. For instance, by evaluating the 50 most representative point mutations, up to 81.9% of endometrial cancers can be identified in the TCGA dataset. At gene level, a 92.9% sensitivity can be obtained by interrogating five genes.DiscussionWe developed a computational method to aid in the selection of relevant genomic biomarkers in endometrial cancer that can be adapted to other cancer types or diseases.     

Comparing trends in cancer rates across overlapping regions

Monitoring and comparing trends in cancer rates across geographic regions or over different time periods have been major tasks of the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) Program as it profiles healthcare quality as well as decides healthcare resource allocations within a spatial-temporal framework. A fundamental difficulty, however, arises when such comparisons have to be made for regions or time intervals that overlap, for example, comparing the change in trends of mortality rates in a local area (e.g., the mortality rate of breast cancer in California) with a more global level (i.e., the national mortality rate of breast cancer). In view of sparsity of available methodologies, this article develops a simple corrected Z-test that accounts for such overlapping. The performance of the proposed test over the two-sample "pooled"t-test that assumes independence across comparison groups is assessed via the Pitman asymptotic relative efficiency as well as Monte Carlo simulations and applications to the SEER cancer data. The proposed test will be important for the SEER * STAT software, maintained by the NCI, for the analysis of the SEER data.     

Sexual functioning in young women in the context of breast cancer treatment

Breast cancer is the most common type of cancer among women worldwide. The number of breast cancer survivors has been growing because of earlier detection and improved treatment. Young women under 50 years of age account for relatively small percentage of all newly diagnosed breast cancer patients. However, their medical and psychosocial context of the disease is unique. Breast cancer is diagnosed at the most productive time in life. Concerns about childbearing, partner rejection, sexual function, body image, sexual attractiveness and career are common. For all these reasons experience of breast cancer diagnosis and treatment among young women requires special attention. Researches indicate that oncological treatment may negatively affect female sexual functioning. Chemotherapy is one of the greatest risk factors of sexual dysfunctions, especially when it results in medication-induced menopause. The duration and severity of sexual problems depend on a wide variety of factors: medical, psychological and interpersonal. These side effects may last for many years after the end of treatment. It is known that breast cancer affects both patients and their partners. The first sexual experience after surgery may be a turning point in sexual adaptation in couples. Communication is crucial in this process. More knowledge about sexual difficulties and sexual adaptation process of young breast cancer survivors (YBCSs) and their partners is needed. Knowing protective and risk factors is necessary to identify couples at risk for sexual dysfunctions in order to professionally support them in the best way and at the right time.     

Impact of universal health care and screening on incidence and survival of Thai women with cervical cancer: A population-based study of the Chiang Mai Province

Universal Health Coverage (UHC) was implemented in Thailand in 2002. This study aims to compare cervical cancer incidence and survival before and after the implementation of UHC, including the national screening program, in the Chiang Mai population in Northern Thailand. Data of women diagnosed with in situ or malignant cervical cancer in Chiang Mai during 1998–2012 were used in our analysis. Annual age-standardized incidence rates (ASR) and age-adjusted relative survival (RS) were estimated for the following three diagnosis periods: period I: 1998–2002 (before UHC), period II: 2003–2007 (UHC implementation) and period III: 2008–2012 (after UHC). The ASR peaked in 2001 at 38 per 100,000, and then subsequently declined to 23 per 100,000 in 2012. The proportion of in situ and localized tumors increased in all age groups, while regional tumors declined. In all women (aged 15–89) with malignant cervical cancer or in situ, the 5-year RS in Period I, Period II and Period III was 73%, 74% and 77%, respectively; when only malignant cases were considered, the RS was 63%, 61% and 62%, respectively. In the screening target women (aged 30–59) with malignant or in situ tumors, the 5-year RS was 84%, 88% and 90%, respectively, in the three periods, while the RS was 71%, 74% and 75%, respectively, in only those with malignant cancers. The introduction of UHC including national cervical cancer screening program has likely reduced the magnitude and severity of cervical cancer and improved the survival of cervical cancer in the screening target age group.     

Stimulatory effect of estrogen on the growth of endometrial cancer cells is regulated by cell-cycle regulators

Estrogen is known as a major risk factor in tumorigenesis of the endometrium. The aim of this study is to establish stable estrogen-responsive endometrial cancer cell lines and to investigate the mechanism of estrogen action, focusing on cell-cycle regulation. Human wild-type estrogen receptor cDNA was transfected into endometrial cancer cells (Ishikawa) and estrogen-responsive cell lines were cloned. Their estrogen responsiveness was evaluated by the effect of estrogen on cellular growth and progesterone receptor expression. It was quantitatively estimated by immunocytochemistry or immunoblotting how the expression of cell-cycle regulators such as cyclin D1, cyclin E, Cyclin A, p53, p21 and p27 was regulated by estrogen. A cell line stably responsive to estrogen was established, and cells proliferated and the glandular structure was formed by estrogen stimulation. Cyclin D1 expression increased at 6–24 h and cyclin A gradually increased until 48 h of estrogen treatment compared with untreated cells. On the other hand, p53 and p21 expressions decreased at 6–24 h, and p27 gradually decreased until 24 h by estrogen. Our results show that the stimulatory effect of estrogen on cell proliferation may be regulated by the up-regulation of cyclin D1 and cyclin A, and down-regulation of p53, p21 and p27. This cell line is useful to clarify the molecular mechanism of estrogen action on endometrial cancer.