Lower Risk Of Cervical Cancer Research Articles

Association between folate level and cervical intraepithelial neoplasia risk: a systematic review and meta-analysis.

There were several studies about the association between folate level and the risk of cervical intraepithelial neoplasia (CIN). This meta-analysis was conducted to evaluate whether folate deficiency is related to a high risk of CIN and cervical cancer. Odds ratios (ORs)/relative risks and 95% confidence intervals (CIs) were summarized regarding the association between folate level and risk of CIN or cervical cancer. The meta-analysis indicated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of CIN, as demonstrated by a random-effects model (OR = 0.42, 95% CI: 0.28-0.62). Conversely, no significant association was found between erythrocyte folate levels and the risk of CIN, as indicated by a random-effects model (OR = 0.69, 95% CI: 0.43-1.12). In addition, random-effects models demonstrated that higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with lower risks of CIN grade 1 and CIN grades 2 or 3, compared with the lowest quartile of serum folate (CIN grade 1: OR = 0.52, 95% CI: 0.29-0.93; CIN grades 2 or 3: OR = 0.33, 95% CI: 0.19-0.58). Higher serum folate levels (the second, third, and fourth quartiles of serum folate) were associated with a lower risk of cervical cancer, compared with the lowest quartile of serum folate (OR = 0.53, 95% CI: 0.36-0.79). Serum low folate levels could increase the risk of CIN and cervical cancer, while erythrocyte folate concentration was not associated with the risk of CIN.

Risk Factors for Cervical Cancer in Ghana.

The major burden of cervical cancer occurs in low- and middle-income countries. In Ghana, it is the second most common cancer among women. Infection with high-risk human papilloma virus (HPV) has been established as the cause of cervical cancer. As such, it is important to identify risk factors that may affect progression from HPV infection to cancer. We assessed the risk factors assocaited with cervical cancer in Ghana. To identify the risk factors for cervical cancer, we conducted an unmatched case-control study in two hospitals in Ghana where most cervical cancer cases are diagnosed. Women with histologically confirmed cervical cancer were the cases, whereas women without cancer seeking care at the two hospitals were controls. A structured questionnaire was administered to the women, after which cervical samples were sent for HPV deoxyribonucleic acid (DNA) testing. Overall, 206 cases and 230 controls were recruited. After adjusting for possible confounders, women with the highest educational level had a significantly lower risk of cervical cancer than those with no or little formal education. Parity was a major risk factor (odd ratio [OR] for five or more children = 7.9; 95% CI: 2.3-27.6), with risk increasing with increasing parity (p for trend <0.001). Women reporting the use of a homemade sanitary towel during menstruation also had an increased risk of cervical cancer compared with women who used a pad (OR: 7.3; 95% CI: 2.5-22.0). In this Ghanaian population, high parity and poor personal hygienic conditions were the main contributing factors to the risk of cervical cancer after adjustment for the presence of high-risk HPV genotypes.

Care cascades following low-value cervical cancer screening in dually enrolled Veterans.

Veterans dually enrolled in the Veterans Health Administration (VA) and Medicare commonly experience downstream services as part of a care cascade after an initial low-value service. Our objective was to characterize the frequency and cost of low-value cervical cancer screening and subsequent care cascades among Veterans dually enrolled in VA and Medicare. This retrospective cohort study used VA and Medicare administrative data from fiscal years 2015 to 2019. The study cohort was comprised of female Veterans aged >65 years and at low risk of cervical cancer who were dually enrolled in VA and Medicare. Within this cohort, we compared differences in the rates and costs of cascade services related to low-value cervical cancer screening for Veterans who received and did not receive screening in FY2018, adjusting for baseline patient- and facility-level covariates using inverse probability of treatment weighting. Among 20,972 cohort-eligible Veterans, 494 (2.4%) underwent low-value cervical cancer screening with 301 (60.9%) initial screens occurring in VA and 193 (39%) occurring in Medicare. Veterans who were screened experienced an additional 26.7 (95% CI, 16.4-37.0) cascade services per 100 Veterans compared to those who were not screened, contributing to $2919.4 (95% CI, -265 to 6104.7) per 100 Veterans in excess costs. Care cascades consisted predominantly of subsequent cervical cancer screening procedures and related outpatient visits with low rates of invasive procedures and occurred in both VA and Medicare. Veterans dually enrolled in VA and Medicare commonly receive related downstream tests and visits as part of care cascades following low-value cervical cancer screening. Our findings demonstrate that to fully capture the extent to which individuals are subject to low-value care, it is important to examine downstream care stemming from initial low-value services across all systems from which individuals receive care.

Optimal Dietary Intake of Riboflavin Associated with Lower Risk of Cervical Cancer in Korea: Korean National Health and Nutrition Examination Survey 2010-2021.

This study aimed to evaluate the association between the dietary intake of vitamin B complex (thiamine, riboflavin, and niacin) and cervical cancer in Korea. The data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2021 were analyzed, which included 28,306 participants who were categorized into non-cervical cancer and cervical cancer groups. The following dietary intake threshold levels of thiamine, riboflavin, and niacin were identified based on the recommended daily allowances (RDAs): thiamine, 1.1 mg/day; riboflavin, 1.2 mg/day; and niacin, 14 mg/day. Among 28,306 participants, 27,976 were in the non-cervical cancer group and 330 were in the cervical cancer group. Riboflavin intakes of more than 1.2 mg/day but less than 2.4 mg/day were associated with a significantly reduced risk of cervical cancer, whereas intakes of above 2.4 mg/day were not associated with cervical cancer. Thiamine and niacin intakes were not significantly related to the risk of cervical cancer. The results of this study suggest that an intake of riboflavin of 1.2-2.4 mg/day may contribute to a lower risk of cervical cancer.

The Role of Methylation of Host and/or Human Papillomavirus (HPV) DNA in Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) Lesions.

Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.

Cervical cancer after the Manchester procedure: a nationwide cohort study.

The Manchester procedure is a successful operation to treat uterine prolapse. However, the influence on cervical cancer remains unknown. We hypothesized a lower risk of cervical cancer after the Manchester procedure. We included all Danish women undergoing the Manchester procedure during 1977-2018 (N = 23,935). Women undergoing anterior colporrhaphy (N = 51,008) were included as references due to comparable health-seeking behaviors. The study cohort is as previously described. We assessed the risk of cervical cancer mortality after the Manchester procedure versus anterior colporrhaphy using cumulated incidence plots and Cox hazard regressions. We applied Fisher's exact test to compare the distribution of histological subtypes after the operations. Generally, few women were diagnosed with cervical cancer (0.1% after Manchester procedure and 0.2% after anterior colporrhaphy). After the Manchester procedure, the risk of cervical cancer was reduced (HR 0.60 [95% CI 0.39-0.94]). Furthermore, we found a slightly reduced risk of overall death (HR 0.96 [95% 0.94-0.99]), but no association regarding death due to cervical cancer (HR 0.66 [95% 0.34-1.25]). The distribution of histological subtypes was not changed. Women undergoing the Manchester procedure are at lower risk of being diagnosed with cervical cancer, while the risk of cancer specific mortality is unchanged compared to women undergoing anterior colporrhaphy. Based on this study, we cannot recommend that women exit ordinary screening programs for human papillomavirus/cervical dysplasia after a Manchester procedure.

Non-adherence to cervical cancer screening recommendations among women in Eswatini: a cross-sectional study

BackgroundIn 2018, Eswatini had the world's highest age-standardised cervical cancer incidence rate. Cervical cancer screening reduces women’s risk of invasive cervical cancer. Data on adherence to cervical cancer screening recommendations in Eswatini are scarce. The purpose of the current study was to determine Eswatini women’s self-reported adherence to cervical cancer screening recommendations, attitudes toward screening, and factors associated with non-adherence.MethodsA cross-sectional survey of women (n = 377) aged 25 to 59 accessing primary healthcare clinics (n = 4) in Eswatini assessed screening participation, attitudes and knowledge regarding cervical cancer screening, and socio-demographic variables. Adjusted logistic regression was used to assess factors associated with non-adherence to Eswatini cervical cancer screening recommendations.ResultsOne hundred and sixty-six (44%) women were classified as adherent to cervical cancer screening recommendations. Attitudinal barriers endorsed by over one-third of participants included a perceived low risk of cervical cancer (n = 161, 43%) and a view that screening is likely to be painful (n = 146, 38%). Participants had higher odds of being classified as non-adherent if they: were single compared with married (OR = 1.78, 95% CI: 1.05, 3.01, p = 0.03), perceived screening as likely painful (OR = 4.43, 95% CI: 2.62, 7.46, p < 0.001); and had not been advised by a doctor/ nurse to screen (OR = 2.82, 95% CI: 1.71, 4.64, p < 0.001). Also, a 1-year increase in age was associated with an increase in the odds of being classified as non-adherent (OR = 1.42, 95% CI: 1.39, 1.45, p = 0.01).ConclusionsSelf-reported adherence was moderate among this group of women. Tailored interventions are needed to increase participation in cervical cancer screening, especially for those women with characteristics associated with being classified as non-adherent. Primary healthcare clinic nurses (and other health providers) may contribute toward improving participation in cervical cancer screening by advising eligible women to screen and providing health education addressing negative attitudes toward screening.

Metformin and Cervical Cancer Risk in Patients with Newly Diagnosed Type 2 Diabetes: A Population-Based Study in Korea.

Cervical cancer is a prevalent malignancy that is a major health problem for women worldwide. The cancer-preventive properties of metformin are well-known, but insufficient data have been reported regarding its relationship to cervical cancer. Therefore, in a nationwide population-based study, we investigated the association between metformin use and cervical cancer incidence in patients with newly diagnosed type 2 diabetes. This retrospective cohort study used the Korean National Health Insurance claims database. Individuals newly diagnosed with type 2 diabetes between January 2005 and December 2009 were included. The occurrence of cervical cancer was explored by matching for age, economic status, region of residence, and use of anti-diabetic medication. In total, 66,013 metformin users and 64,756 non-users were analyzed. Cervical cancer occurred in 219 metformin users (0.33%) and 274 metformin non-users (0.42%) (hazard ratio [HR], 0.783; 95% confidence interval [CI], 0.655 to 0.036; P=0.007). Moreover, cervical cancer risk was considerably reduced in those treated with a high dose (>1,200,000 mg) or for an extended period (≥2,000 days) compared to non-users (HR, 0.151; 95% CI, 0.093 to 0.243; P<0.001; and HR, 0.141; 95% CI, 0.077 to 0.258; P<0.001). The incidence was also significantly lower in metformin users among those over 50 years old (HR, 0.791; 95% CI, 0.650 to 0.961; P<0.001). Metformin use in patients with newly diagnosed diabetes was associated with a lower risk of cervical cancer in Korea. Furthermore, a significant association was found between the use of metformin and cervical cancer in a dose- and duration-dependent manner and among those over 50 years old.

Genetic Variability in the E6, E7, and L1 Genes of Human Papillomavirus Types 16 and 18 among Women in Saudi Arabia.

Cervical cancer is the eighth most frequent cancer in Saudi Arabia, and most cases are associated with human papillomavirus (HPV) types 16 and 18. HPV-induced carcinogenesis may be associated with the intra-type variant, genetic mutation, or the continuous expression of viral oncogenes E6 and E7. Infection efficiency and virus antigenicity may be affected by changes in the L1 gene. Thus, this retrospective cohort study analyzed E6, E7, and L1 gene mutations in cervical specimens collected from Saudi women positive for HPV16 or HPV18 infection. HPV16 and HPV18 lineages in these specimens were predominantly from Europe. The L83V mutation in the E6 gene of HPV16 showed sufficient oncogenic potential for progression to cervical cancer. By contrast, the L28F mutation in the E7 gene of HPV16 was associated with a low risk of cervical cancer. Other specific HPV16 and HPV18 mutations were associated with an increased risk of cancer, cancer progression, viral load, and age. Four novel mutations, K53T, K53N, R365P, and K443N, were identified in the L1 gene of HPV16. These findings for HPV16 and HPV18 lineages and mutations in the E6, E7, and L1 genes among women in Saudi Arabia may inform the design and development of effective molecular diagnostic tests and vaccination strategies for the Saudi population.

Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology.

Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology. We wanted to investigate the detection rate of CIN3+ in women 25-39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology. During 2014-2017, samples from 13,021 women 25-39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021. Of the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413). By testing women 25-39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.

A Machine Learning-Based Framework for the Prediction of Cervical Cancer Risk in Women

One of the most common types of cancer in women is cervical cancer, a disease which is the most prevalent in poor nations, with one woman dying from it every two minutes. It has a major impact on the cancer burden in all cultures and economies. Clinicians have planned to use improvements in digital imaging and machine learning to enhance cervical cancer screening in recent years. Even while most cervical infections, which generate positive tests, do not result in precancer, women who test negative are at low risk for cervical cancer over the next decade. The problem is determining which women with positive HPV test results are more likely to have precancerous alterations in their cervical cells and, as a result, should have a colposcopy to inspect the cervix and collect samples for biopsy, or who requires urgent treatment. Previous research has suggested techniques to automate the dual-stain assessment, which has significant clinical implications. The authors reviewed previous research and proposed the cancer risk prediction model using deep learning. This model initially imports dataset and libraries for data analysis and posts which data standardization and basic visualization was performed. Finally, the model was designed and trained to predict cervical cancer, and the accuracy and performance were evaluated using the Cervical Cancer dataset.

Awareness of the non-contraceptive benefits of reversible contraceptive methods in a cohort of Brazilian women: an exploratory study

Purpose We assess the awareness of Brazilian women about non-contraceptive benefits of contraceptives and compare non-health with health care providers. Material and methods We conducted a survey in Brazil using a questionnaire administered via Google Forms asking women to respond about the awareness of non-contraceptive benefits of combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS), etonogestrel (ENG)-implant, copper intrauterine device (Cu-IUD), and male condom. Results We received 2,068 completed questionnaires, 720 women (34.8%) aged ≤ 29 years and 236 (11.4%) were physicians or nurses. Only one third of the respondents were aware that COC use is associated with decreased risks of ovarian and endometrial cancers; 296 (16.1%) about that the use of DMPA is associated with a decreased risk of endometrial cancer, and 253 (13.8%) were aware about that the users of the Cu-IUD present lower risk of cervical cancer. We identified significant differences between non-health care providers when compared to physicians or nurses. Conclusions We found low awareness regarding the associated lower risk of ovarian, endometrial and cervical cancer associated with the use of some contraceptives, evidencing the need to provide more information about the non-contraceptive benefits during training for health care providers.

Cervical Cancer Screening Outcomes Among a Sample of Low-Income Uninsured Women: A Program-Based Study.

Background: Most studies examining cervical cancer screening outcomes have focused on either an age-specific diagnosis and outcomes of abnormal smears or frequency of abnormal outcomes among a sample of insured women. Thus, it is unclear what the distribution outcomes would be when other sociodemographic characteristics are considered. This study examines the variation in cervical cancer screening outcomes and sociodemographic characteristics (patients' age, marital status, race/ethnicity, rurality, and Papanicolaou [Pap] test screening history) within a sample of low-income and uninsured women.Materials and Methods: Our grant-funded program provided 751 Pap tests, 577 human papillomavirus (HPV) tests, and 262 colposcopies to 841 women between 2013 and 2019. Observed outcomes for each procedure type were cross-tabulated by patients' sociodemographic characteristics. Chi-squared and Fisher's exact tests were used to test the independence of screening outcomes and sociodemographic characteristics.Results: The overall positivity rate was 7.2% for Pap tests (n = 54/751), 3.6% for HPV tests (n = 21/577), and 44.7% for colposcopies (n = 117/262). Significance tests suggested that the Pap test and colposcopy outcomes we observed were independent of sociodemographic characteristics in all but one instance—Pap test outcomes were not independent of patient age (p = 0.009). Moreover, the Pap test positivity rate increased with patient age.Conclusions: Our findings support recommendations to discontinue screening for women older than 65 years at low risk for cervical cancer. Our ability to identify an association between cervical screening outcomes and other sociodemographic characteristics may have been limited by our small sample size. This highlights an important barrier to studying health outcomes within low-income and uninsured populations, which are often missing in larger research data sets (e.g., claims).

The association between rs1800872 polymorphism in interleukin-10 and risk of cervical cancer: A meta-analysis.

Background:In recent years, several reports have tried to prove this connection between rs1800872 polymorphism in interleukin-10 and cervical cancer among different populations, but the results are debatable. Thus, we collected all the published literature and conducted an integrated meta-analysis, which provided better evidence-based medicine for the relationship between rs1800872 polymorphism in interleukin-10 and risk of cervical cancer.Methods:We systematically performed our search on PubMed, EMBASE, Web of Science, WanFang database, and CNKI for all papers related to this research, published up to August 1, 2020. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant, and recessive model to appraise the association.Results:The meta-analysis included 8 studies containing 1393 cervical cancer cases and 1307 controls. The aggregate data under heterozygous model and dominant inheritance model (OR = 0.66, 95% CI: 0.55--0.80) indicated a significant association between rs1800872 and the low risk of cervical cancer in the entire population. And the aggregated data under the dominant inheritance model shows that rs1800872 is significantly associated with the reduction in the risk of cervical tumors in the entire population.Conclusion:Our conclusion is that the AC/AA + AC variant of Rs1800872 indicates a protective effect in the development of cervical cancer.

The ECCR1 rs11615, ERCC4 rs2276466, XPC rs2228000 and XPC rs2228001 polymorphisms increase the cervical cancer risk and aggressiveness in the Bangladeshi population

BackgroundMultiple studies around the world revealed that genetic polymorphism in different genes of the DNA repair system might affect the DNA repair capabilities and accelerate the chances of cervical cancer (CC) development. Therefore, we aimed to evaluate the association of DNA repair gene- ECCR1 rs11615, ERCC4 rs2276466, XPC rs2228000 and rs2228001 polymorphisms and CC susceptibility in the Bangladeshi population. MethodsA case-control genetic association study was conducted among 210 patients with diagnostically confirmed CC and 200 healthy volunteers. The p-value and OR (odds ratios) with 95% CI (confidence interval) were evaluated to get the level of association. ResultsAfter the individual analysis of all SNPs, we noticed that ECCR1 rs11615 possessed a significantly lower risk, whereas ERCC4 rs2276466 possessed a significantly elevated risk of CC in all genetic models (p < 0.05). XPC rs2228000 showed a significantly lower risk of CC in TC, TC + CC genotypes and allele model (OR = 0.61, p = 0.025; OR = 0.61, p = 0.019 and OR = 0.67, p = 0.027, respectively), whereas XPC rs2228001 possessed a significantly elevated risk of CC in CA, CA + AA genotypes and allele model (OR = 1.67, p = 0.012; OR = 1.69, p = 0.009 and OR = 1.42, p = 0.022). Besides, ERCC4 rs2276466 (Grade III vs. I + II: OR = 4.01, p = 0.003) and XPC rs2228001 (Grade III vs. I + II: OR = 3.38, p = 0.003) were connected with high tumor aggressiveness and ERCC4 rs2276466 was also showed a lower risk of CC development in the younger population (<45 years). ConclusionThe findings supported that rs2276466 and rs2228001 polymorphisms increase CC development and aggressiveness, whereas rs11615 and rs2228000 lower the CC risk in the studied population.

Endometriosis and cancer: a systematic review and meta-analysis.

Endometriosis is an often chronic, inflammatory gynaecologic condition affecting 190 million women worldwide. Studies have reported an elevated cancer risk among patients with endometriosis. However, prior research has included methodologic issues that impede valid and robust interpretation. We conducted a meta-analysis of studies investigating the association between endometriosis and cancer risk and analysed the results by methodologic characteristics. We discuss the implications of cancer screening in patients and management challenges faced by clinicians. We searched PubMed and Embase databases for eligible studies from inception through 24 October 2019. We included cohort and case-control studies examining the association between endometriosis and cancer risk; cross-sectional studies and case reports were excluded. Publications had to present risk/rate/odds estimates with 95% CI. Random effects meta-analysis was used to estimate summary relative risks (SRR) and CIs. Heterogeneity across studies was assessed by the Q test and I2 statistics, and publication bias using Egger's and Begg's tests. Risk of bias and quality of the included studies were assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Forty-nine population-based case-control and cohort studies were included. Twenty-six studies were scored as having a 'serious'/'critical' risk of bias, and the remaining 23 'low'/'moderate'. Cancer-specific analyses showed a positive association between endometriosis and ovarian cancer risk (SRR = 1.93, 95% CI = 1.68-2.22; n = 24 studies) that was strongest for clear cell (SRR = 3.44, 95% CI = 2.82-4.42; n = 5 studies) and endometrioid (SRR = 2.33, 95% CI = 1.82-2.98; n = 5 studies) histotypes (Pheterogeneity < 0.0001), although with significant evidence of both heterogeneity across studies and publication bias (Egger's and Begg's P-values < 0.01). A robust association was observed between endometriosis and thyroid cancer (SRR = 1.39, 95% CI =1.24-1.57; n = 5 studies), a very small association with breast cancer (SRR = 1.04, 95% CI =1.00-1.09; n = 20 studies) and no association with colorectal cancer (SRR = 1.00, 95% CI =0.87-1.16; n = 5 studies). The association with endometrial cancer was not statistically significant (SRR = 1.23, 95% CI =0.97-1.57; n = 17 studies) overall and wholly null when restricted to prospective cohort studies (SRR = 0.99, 95% CI =0.72-1.37; n = 5 studies). The association with cutaneous melanoma was also non-significant (SRR = 1.17, 95% CI =0.97-1.41; n = 7 studies) but increased in magnitude and was statistically significant when restricted to studies with low/moderate risk of bias (SRR = 1.71, 95% CI = 1.24-2.36, n = 2 studies). The most robust finding both in terms of statistical significance and magnitude of effect was an inverse association with cervical cancer (SRR = 0.68, 95% CI =0.56-0.82; n = 4 studies); however, this result has a high potential to reflect heightened access to detection of dysplasia for women who reached an endometriosis diagnosis and is thus likely not causal. Several additional cancer types were explored based on <4 studies. Endometriosis was associated with a higher risk of ovarian and thyroid, and minimally (only 4% greater risk) with breast cancer, and with a lower risk of cervical cancer. However, this meta-analysis confirms that: a majority of studies had severe/critical risk of bias; there is impactful heterogeneity across studies-and for ovarian cancer, publication bias; and causal inference requires temporality, which in many studies was not considered. We discuss the implications of these potential associations from the perspectives of patients with endometriosis, clinicians involved in their care, and scientists investigating their long-term health risks.

Association of Low-Value Testing With Subsequent Health Care Use and Clinical Outcomes Among Low-risk Primary Care Outpatients Undergoing an Annual Health Examination

The association of low-value testing with downstream care and clinical outcomes among primary care outpatients is unknown to date. To assess the association of low-value testing with subsequent care among low-risk primary care outpatients undergoing an annual health examination (AHE). This population-based retrospective cohort study used administrative health care claims from Ontario, Canada, for primary care outpatients undergoing an AHE between April 1, 2012, and March 31, 2016, to identify individuals who could be placed into one (or more) of the following 3 cohorts: adult patients (18 years or older) at low risk for cardiovascular and pulmonary disease, adult patients at low risk for cardiovascular disease, and female patients (aged 13-20 years or older than 69 years) at low risk for cervical cancer. The dates of analysis were June 3 to September 12, 2019. Low-value screening tests were defined per cohort as (1) a chest radiograph within 7 days, (2) an electrocardiogram (ECG) within 30 days, or (3) a Papanicolaou test within 7 days after an AHE. Subsequent specialist visits, diagnostic tests, and procedures within 90 days after a low-value test (if the patient had a chest radiograph, ECG, or Papanicolaou test) or end of the exposure observation window (if not tested). Included in the chest radiograph, ECG, and Papanicolaou test cohorts of propensity score-matched pairs were 43 532 patients (mean [SD] age, 47.5 [14.4] years; 38.5% female), 245 686 patients (mean [SD] age, 49.9 [13.7] years; 51.1% female), and 29 194 patients (mean [SD] age, 45.5 [27.1] years; 100% female), respectively. At 90 days, chest radiographs in low-risk patients were associated with an additional 0.87 (95% CI, 0.69-1.05) and 1.96 (95% CI, 1.71-2.22) patients having an outpatient pulmonology visit or an abdominal or thoracic computed tomography scan per 100 patients, respectively, and ECGs in low-risk patients were associated with an additional 1.92 (95% CI, 1.82-2.02), 5.49 (95% CI, 5.33-5.65), and 4.46 (95% CI, 4.31-4.61) patients having an outpatient cardiologist visit, a transthoracic echocardiogram, or a cardiac stress test per 100 patients, respectively. At 180 days, Papanicolaou testing in low-risk patients was associated with an additional 1.31 (95% CI, 0.84-1.78), 52.8 (95% CI, 51.9-53.6), and 0.84 (95% CI, 0.66-1.01) patients having an outpatient gynecology visit, a follow-up Papanicolaou test, or colposcopy per 100 patients, respectively. Observed associations in this population-based cohort study suggest that testing in low-risk patients as part of an AHE increases the likelihood of subsequent specialist visits, diagnostic tests, and procedures.

Evidence based appropriate triage strategies for implementing high risk HPV as primary technology in cervical cancer screening.

Primary cervical cancer screening by HPV testing for high risk human papillomavirus (hrHPV) is expected to replace cytology-based programs in many parts of the world. Its high sensitivity and negative predictive value permit longer screening intervals up to beyond five years. However, low positive predictive value can lead to unnecessary referrals and overtreatment since most hrHPV infections are transient and will not develop disease. Therefore risk stratification is needed to effectively triage and identify women among the hrHPV positives, who are at an increased risk of cervical (pre)cancer who need further diagnostic evaluation to decide on further management. Several triage strategies like HPV16/18 genotyping, p16/Ki67 dual staining and DNA methylation markers (CADM1, MAL and miR-124-2) have been evaluated to determine suitable triage options. Triage with p16/Ki-67 dual-stain provided better long-term risk stratification than cytology with significant reduction in cumulative 5 years CIN3+ risk in p16/Ki-67 negative women. DNA methylation assays have shown higher specificity than cytology and higher sensitivity than HPV16/18 genotyping with added advantages of reproducibility and application on self-collected samples. Based on current evidence, Pap cytology with or without additional HPV16/18 genotyping remains the most recommended triage strategies for primary HPV screening. Other strategies will need more longitudinal studies to provide evidence of risk reduction in test negative results. WHO recommends Visual Inspection with Acetic Acid (VIA) for triaging HPV-positive women in LMIC settings. An optimal triage strategy that can be integrated with primary HPV screening should be able to segregate and reassure the large majority of women who are at very low risk of cervical cancer.

Polymorphisms in endoplasmic reticulum aminopeptidase genes are associated with cervical cancer risk in a Chinese Han population

BackgroundAntigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that polymorphisms in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of diseases. In the current study, we evaluated the influence of ERAP gene (ERAP1 and ERAP2) polymorphisms on susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer.MethodsSix single nucleotide polymorphisms (SNPs) in ERAP1 and 5 SNPs in ERAP2 were selected and genotyped in 556 CIN patients, 1072 cervical cancer patients, and 1262 healthy control individuals. Candidate SNPs were genotyped using SNaPshot assay. And the association of these SNPs with CIN and cervical cancer was analysed.ResultsThe results showed that allelic and genotypic frequencies of rs26653 in ERAP1 were significantly different between cervical cancer and control groups (P = 0.001 and 0.004). The allelic frequencies of rs27044 in ERAP1 and rs2287988 in ERAP2 were significantly different between control and cervical cancer groups (P = 0.003 and 0.004). Inheritance model analysis showed that genotypes of rs27044, rs26618, rs26653 and rs2287988 SNPs may be associated with the risk of cervical cancer (P = 0.003, 0.004, 0.001 and 0.002). Additionally, haplotype analysis results showed that the ERAP1 haplotype, rs27044C-rs30187T-rs26618T-rs26653G-rs3734016C, was associated with a lower risk of cervical cancer (P = 0.001). The ERAP2 haplotypes rs2549782G- rs2548538A-rs2248374A-rs2287988G-rs1056893T (P = 0.009 and 0.006) and rs2549782T-rs2548538T-rs2248374G-rs2287988A-rs1056893T (P = 0.003 and 0.009) might be associated with cervical cancer and the development from CIN to cervical cancer.ConclusionOur results indicated that rs27044, rs26618 and rs26653 in ERAP1 and rs2287988 in ERAP2 influenced susceptibility to cervical cancer.

Telomere length in cervical exfoliated cells, interaction with HPV genotype, and cervical cancer occurrence among high-risk HPV-positive women.

BackgroundAlthough high‐risk human papillomavirus (HR‐HPV) infection is recognized as the main cause of cervical cancer, only a minority of HPV‐infected women develop this malignancy. Increasing evidence suggests that alterations of telomere length might be implicated in carcinogenesis. However, the association between cervical cancer and telomere length remains unknown.MethodsThis case‐control study included 591 cervical cancer patients and 373 cancer‐free controls, all of whom were infected with HR‐HPV. Relative telomere length (RTL) in cervical cancer exfoliated cells was measured by quantitative PCR. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression analysis.ResultsHPV16, 18, 52, and 58 were common in both case and control groups. The proportion of HPV16 infection tended to increase across the quartiles of RTL (P trend < 0.001). There was no statistically significant association of RTL with tumor differentiation, histological type, and FIGO stage. After adjustment for age and HPV types, the lowest quartile of RTL presented a 49% lower risk (OR = 0.51, 95% CI: 0.35, 0.76; P < 0.001) than those with the highest quartile of RTL. There was also a dose‐response relationship of shorter RTL on lower risk of cervical cancer (P trend < 0.001).ConclusionShortened telomere length in cervical exfoliated cells was related to the lower risk of cervical cancer among HR‐HPV‐positive women, which might help to improve cervical cancer screening and surveillance. Further prospective studies with large sample should be designed to validate our preliminary findings, and evaluate the potential efficacy of telomere length for cervical cancer screening.