Cervical Cancer Causation Research Articles

Myths and common misbeliefs about cervical cancer causation among Palestinian women: a national cross-sectional study.

Cervical cancer (CC) myths and beliefs can negatively impact women's preventive behaviors, including vaccination against human papillomavirus and having regular screening tests. This study aimed to examine awareness of Palestinian women about myths related to CC causation and investigated factors associated with good awareness. A national cross-sectional study was conducted to recruit adult Palestinian women from hospitals, primary healthcare facilities, and public areas in 11 Palestinian governorates. A translated-into-Arabic version of the Cancer Awareness Measure-Mythical Causes Scale was used to collect data. Awareness level was determined based on the number of CC myths around CC causation recognized to be incorrect: poor (0-4), fair (5-9), and good (10-13). A total of 7058 questionnaires were included. Myths unrelated to food were more commonly recognized as incorrect compared to those related to food. The most recognized food-unrelated myth was 'having a physical trauma' (n = 3714, 52.6%), whereas the least recognized was 'using mobile phones' (n = 2238, 31.7%). The most recognized food-related myth was 'drinking from plastic bottles' (n = 2708, 38.4%), whereas the least recognized was 'eating food containing additives' (n = 1118, 15.8%). Only 575 participants (8.1%) displayed good awareness and promptly recognized at least 10 out of 13 myths around CC causation as incorrect. Factors associated with lower likelihood of displaying good awareness of myths around CC causation included living in the West Bank and Jerusalem, being married, widowed or divorced, knowing someone with cancer, and visiting hospitals or primary healthcare centers. A very small proportion of Palestinian women recognized 10 or more myths around CC causes as incorrect. Initiatives addressing CC myths are needed in the Palestinian community.

A questionnaire-based survey to assess knowledge and practice of health care workers regarding genital hygiene: from a rural tertiary hospital in India

ABSTRACT Purpose Maintaining good genital hygiene is an important component in reducing human papilloma virus (HPV) infections and its sequelae such as cervical pre-cancer and cancer. Awareness on the exact practice of maintaining genital hygiene is important as they are different in men and women, and both are equally important in reducing genital HPV infections. Study Design A questionnaire-based survey was undertaken to assess knowledge and practice of cervical cancer and its relationship with genital hygiene. Interns, post graduate students, consultants, and nurses were invited. Domain-based assessment was done. Correlation between the domains was performed using Pearson’s coefficient. Results 87 respondents completed the questionnaire. Six domains on awareness of physical and genital hygiene, cervical cancer causation and prevention, health education and personal experience of cervical cancer were explored. In the awareness domains, the response was uniformly poor in 45–50% of respondents. Nurses had poor knowledge in every domain of the questionnaire. Conclusions There is an urgent need to improve and bridge the gap of knowledge and practice in hygiene and cervical cancer. This is necessary since nurses and interns are the first line for disseminating proper information to the general public. Webinars, seminars, and continued medical education (CME) programs must be included in the training curricula to impart knowledge on genital hygiene and cervical cancer.

High parity is associated with increased risk of cervical cancer: Systematic review and meta-analysis of case-control studies.

Background:Cervical cancer is the fourth most common cancer among women. High parity has long been suspected with an increased risk of cervical cancer. Evidence from the existing epidemiological studies regarding the association between parity and cervical cancer is variable and inconsistent. Therefore, the objective of this systematic review and meta-analysis was to synthesize the best available evidence on the epidemiological association between parity and cervical cancer.Methods:Case–control studies reporting the association between parity and cervical cancer were systematically searched in databases like MEDLINE/PubMed, HINARI, Google scholar, Science direct, and Cochrane Libraries. All studies fulfilling the inclusion criteria and published between 2000 and 7 March 2020 were included in this meta-analysis. This study reported according to PRISMA guideline. Cochran’s Q-statistics and I2 tests were performed to assess heterogeneity among included studies. Egger’s regression analysis was performed to assess publication bias. A random-effect meta-analysis model was used to compute pooled odds ratio of the association between parity and cervical cancer.Results:A total of 6685 participants (3227 patients and 3458 controls) were incorporated in the 12 studies included in this meta-analysis. The meta-analysis revealed that women with high parity had 2.65 times higher odds of developing cervical cancer compared to their counterparts (odds ratio = 2.65, 95% confidence interval = 2.08–3.38).Conclusion:High parity is positively associated with cervical cancer. Strong epidemiological studies are recommended to further explore the mechanisms and role of parity in the causation of cervical cancer.

Human Papillomavirus (HPV): unawareness of the causal role of HPV infection in cervical cancer, HPV vaccine availability, and HPV vaccine uptake among female schoolteachers in a Middle Eastern country

BackgroundHuman papillomavirus (HPV) is the most common viral infection of the reproductive tract. This cross-sectional study among female schoolteachers assessed the prevalence of i) unawareness of HPV infection’s causal role in cervical cancer; ii) unawareness of HPV vaccine availability and iii) examined the sociodemographic variables associated both the outcome variables. MethodsThis cross-sectional study was conducted among female schoolteachers employed in public and private sectors schools in Kuwait using a structured questionnaire for data collection. Prevalence of each of the outcome variables was computed. Multivariable logistic regression analyses were used to evaluate independent predictors of two dependent variables. ResultsA total 1341 female schoolteachers were enrolled. Of the participants, 60% were unaware of HPV causal role in cervical cancer and 88% were unaware of HPV vaccine availability. Among those who were aware of HPV vaccine availability, 83.8% were unvaccinated. Multivariable logistic regression (MLR) model showed that 20–29 years old participants or those with low family income (< 500 KD/month) were significantly (p < 0.05) more likely to be unaware of HPV causal role in cervical cancer. Moreover, participants with family/ personal history of cervical cancer were significantly (p < 0.05) less likely to be unaware of HPV role in causation of cervical cancer. A separate MLR model revealed that the participants were significantly more likely to be unaware of HPV vaccine availability if they were Kuwaiti nationals or non-Kuwaiti Arabs (p < 0.05), employed in public schools (p = 0.003) or less likely to be unaware if they had personal or family history of cervical cancer (p < 0.001). ConclusionHigh prevalences of unawareness of causal role of HPV in cervical cancer and unawareness of HPV vaccine availability were recorded. Targeted education among identified sociodemographic groups with high levels of unawareness is warranted. If undertaken, future studies may evaluate the impact of recommended efforts.

Hong Kong Chinese women's lay beliefs about cervical cancer causation and prevention.

This study aimed to seek insights into Chinese women's lay beliefs about cervical cancer causal attributions and prevention. Twenty-three new immigrant adult women from Mainland China and thirty-five Hong Kong adult women underwent semi-structured in-depth interviews. Interviews were audio taped, transcribed and analyzed using a Grounded Theory approach. This study generated three foci: causal beliefs about cervical cancer, perceived risk of cervical cancer, and beliefs about cervical cancer prevention. Personal risky practices, contaminated food and environment pollution were perceived as the primary causes of cervical cancer. New immigrant women more likely attributed cervical cancer to external factors. Most participants perceived cervical cancer as an important common fatal female cancer with increased risk/prevalence. Many participants, particularly new immigrant women participants, expressed helplessness about cervical cancer prevention due to lack of knowledge of prevention, it being perceived as beyond individual control. Many new immigrant participants had never undergone regular cervical screening while almost all Hong Kong participants had done so. Some Chinese women hold pessimistic beliefs about cervical cancer prevention with inadequate knowledge about risk factors. Future cervical cancer prevention programs should provide more information and include capacity building to increase Chinese women's knowledge and self-efficacy towards cervical cancer prevention.

Cultural beliefs and understandings of cervical cancer among Mexican immigrant women in Southeast Georgia.

Rural Mexican immigrant women in the U.S. are infrequently screened and experience health disparities from cervical cancer. We explored cancer-related cultural beliefs in this population. We administered a cross-sectional survey to 39 Mexican immigrant women due for screening. We conducted univariate and bivariate analyses of participants' characteristics, Pap test history, cancer-related knowledge and beliefs, and cultural consensus analysis about causes of cervical cancer and barriers to screening. For all the cultural consensus tasks, there was consensus (Eigenratios >3:1) among survey participants. Comparing the rankings of risk factor clusters, clusters related to sexual behaviors were ranked more severely than clusters related to genetic or other behavioral factors. There was agreement on ideas of cervical cancer causation and barriers to screening among these women. Hence, improved methods of disseminating important health information and greater access to care are needed, particularly in relationship to stigma about sex and birth control practices.

Understanding the transcriptional regulation of cervix cancer using microarray gene expression data and promoter sequence analysis of a curated gene set

Cervical cancer, the malignant neoplasm of the cervix uteri is the second most common cancer among women worldwide and the top-most cancer in India. Several factors are responsible for causing cervical cancer, which alter the expression of oncogenic genes resulting in up or down-regulation of gene expression and inactivation of tumor-suppressor genes/gene products. Gene expression is regulated by interactions between transcription factors (TFs) and specific regulatory elements in the promoter regions of target genes. Thus, it is important to decipher and analyze TFs that bind to regulatory regions of diseased genes and regulate their expression. In the present study, computational methods involving the combination of gene expression data from microarray experiments and promoter sequence analysis of a curated gene set involved in the cervical cancer causation have been utilized for identifying potential regulatory elements. Consensus predictions of two approaches led to the identification of twelve TFs that might be crucial to the regulation of cervical cancer progression. Subsequently, TF enrichment and oncomine expression analysis suggested that the transcription factor family E2F played an important role for the regulation of genes involve in cervical carcinogenesis. Our results suggest that E2F possesses diagnostic/prognostic value and can act as a potential drug target in cervical cancer.

Baseline human papillomavirus infection, high vaginal parity, and their interaction on cervical cancer risks after a follow-up of more than 10 years

Human papillomavirus (HPV) has been recognized as a major factor for cervical cancer causation. Other factors, relating to reproduction, are also important. This study aims to disentangle the roles of baseline HPV infection, high vaginal parity (defined as having ≥4 vaginal deliveries), and the interaction between the two in predicting cervical cancer risk. The authors apply a newly developed causal-pie modeling technique to analyze a cohort of more than 10,000 women conducted in Taiwan with more than 10years of follow-up. The rate ratios adjusted by age and menopausal status were further modeled by an additive Poisson regression with non-negative parameters. The index of causal-pie weight (CPW) was calculated to indicate the proportion of cervical cancer cases attributable to a particular class of causal pies. It was found that the CPWs are 36.3% for baseline HPV infection, 35.6% for baseline HPV infection and high vaginal parity, and 28.1% for other factors. A causal-pie modeling based on a women cohort in Taiwan successfully disentangles the roles of virus factors and reproductive factors at study entry, independently or interactively, on subsequent cervical cancer risk.

CCDB: a curated database of genes involved in cervix cancer

The Cervical Cancer gene DataBase (CCDB, http://crdd.osdd.net/raghava/ccdb) is a manually curated catalog of experimentally validated genes that are thought, or are known to be involved in the different stages of cervical carcinogenesis. In spite of the large women population that is presently affected from this malignancy still at present, no database exists that catalogs information on genes associated with cervical cancer. Therefore, we have compiled 537 genes in CCDB that are linked with cervical cancer causation processes such as methylation, gene amplification, mutation, polymorphism and change in expression level, as evident from published literature. Each record contains details related to gene like architecture (exon–intron structure), location, function, sequences (mRNA/CDS/protein), ontology, interacting partners, homology to other eukaryotic genomes, structure and links to other public databases, thus augmenting CCDB with external data. Also, manually curated literature references have been provided to support the inclusion of the gene in the database and establish its association with cervix cancer. In addition, CCDB provides information on microRNA altered in cervical cancer as well as search facility for querying, several browse options and an online tool for sequence similarity search, thereby providing researchers with easy access to the latest information on genes involved in cervix cancer.

Weaving meaning? An exploration of the interplay between lay and professional understandings of cervical cancer risk

In line with the increasing emphasis on informed choice, women invited for cervical cancer screening in England receive a leaflet containing information on the risk factors and causation of the condition. However, data from a qualitative interview study with 35 women suggest that the ways in which women make sense of this information can vary and frequently do not correspond to the causal pathways and explanations which characterise contemporary professional medical explanations. This paper examines the complex interplay between lay and professional understandings that takes place as women attempt to weave the information they receive, their prior understandings and contextual factors together into some kind of coherent framework, in which each piece of information makes sense in relation to everything else. We conclude by arguing that, while presenting full and accurate information about orthodox medical understandings of cervical cancer causation in an accessible way maybe challenging, partial presentation of ‘the facts’ is likely to be ineffective.

Familial Risks for Cervical Tumors in Full and Half Siblings: Etiologic Apportioning

Many studies have shown familial aggregation for cervical cancer, but they have been unable to distinguish between shared environmental and genetic effects. Full and half-siblings were identified from the nationwide Swedish Family-Cancer Database, including invasive and in situ cervical cancers in women up to age 70 years. Half-siblings were defined through a common father or mother. Standardized incidence ratios, adjusted for several variables, were calculated for proband-wise risks between full and half-siblings. The familial risk for full siblings was 1.84, compared with 1.40 for maternal and 1.27 for paternal half-siblings. These data were used to apportion familial risk for cervical tumors in full siblings into a heritable component, accounting for 64%, and an environmental component, accounting for 36% of the total risk. No evidence for gene-environment interactions was found. The intractable difficulty in separating cervical cancer causation will be an obstacle for a successful identification of susceptibility genes.

The interaction between steroid hormones, human papillomavirus type 16, E6 oncogene expression, and cervical cancer

Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6andE7) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss ofp53gene-mediated cell apoptosis. A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the steroid arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa, &amp; C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16E6gene expression was present in 79% (n= 23) and 88% (n= 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16E6*Igene and 30 patients with expression of theE6*IIgene. There were 57% of steroid users (n= 17) who had expression of theE6*I/E6*IIgene, compared to 52% (n= 17) of nonusers (P= 0.800). From a molecular level, this study does not confirm the role of injectable progesterones in cervical carcinogenesis.

The interaction between steroid hormones, human papillomavirus type 16, E6 oncogene expression, and cervical cancer.

Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6 and E7 ) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss of p53 gene-mediated cell apoptosis. A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the steroid arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa, & C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16 E6 gene expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene, compared to 52% (n = 17) of nonusers (P = 0.800). From a molecular level, this study does not confirm the role of injectable progesterones in cervical carcinogenesis.

Risk factors for cervical cancer in Colombia and Spain.

A population-based case-control study of cervical cancer was conducted in Spain and Colombia to assess the relationship between cervical cancer and exposure to human papillomavirus (HPV), selected aspects of sexual and reproductive behaviour, use of oral contraceptives, screening practices and smoking. The study included 436 cases of histologically confirmed squamous-cell carcinoma and 387 age-stratified controls randomly selected from the general population that generated the cases. The presence of HPV DNA in cervical scrapes was assessed by PCR-based methods and was the strongest risk factor (OR = 23.8; 13.4-42.0). Risk estimates for any other factor were only slightly modified after adjusting for HPV status. Among women found positive for HPV DNA, only the use of oral contraceptives was a risk factor for cervical cancer (OR = 6.5; 1.3-31.4 for ever vs. never use). Patients with cervical cancer who were HPV DNA-negative retained most of the established epidemiological features of this disease. This suggests that some instances of HPV infection went undetected or that other sexually transmitted factor(s) contribute to the causation of cervical cancer. Early age at first intercourse (OR = 4.3; 2.1-9.0 for age < 16 vs. 24+) and early age at first birth (OR = 5.0; 1.8-14.2 for age < 16 vs. 24+) were associated with increased risk of cervical cancer; these effects were independent of one another. Low educational level was a risk factor (OR = 2.5; 1.6-3.9). Number of sexual partners was in our study a surrogate for HPV infection. Smoking and parity after age 24 were weakly and inconsistently associated with the risk of cervical cancer. Previous screening (OR = 0.7; 0.5-1.0) and ever having undergone a Caesarean section (OR = 0.4; 0.2-0.8) were protective factors.

Association of oral contraceptive use and human papillomaviruses in invasive cervical cancers

In a study of 197 cases of histologically confirmed invasive cervical cancer, 61% of biopsies were positive for human papillomavirus (HPV) DNA by Southern or dot-blot hybridization. An association between detection of HPV DNA and oral contraceptive use was observed when HPV-positive and -negative cases were compared. Women reporting recent or long-term (greater than 4 yrs) oral contraceptive use were at 2.3 and 2.9-fold increased risks of HPV positivity, respectively. An increased risk of HPV positivity was also associated with formal education and with urban residence, while long-term smoking was negatively associated with HPV detection. A non-significant trend of increasing risk of HPV positivity with increasing number of sexual partners of the women and of the male partners of monogamous women was observed. Detection of HPV DNA was not associated with other cervical cancer risk factors examined, including age at first coitus, number of pregnancies, and Pap smear screening history. Our findings suggest either an interaction between HPV infection and oral contraceptive use in the genesis of cervical cancer or an increased expression of HPV genome in neoplasms of oral contraceptive users. These observations also support a multifactorial model of cervical cancer causation.

1 - The Causation of Cervical Cancer: Part I: A General Review

The causation of cervical cancer is conveniently discussed by using themes emergent from a great volume of field studies and by using the manner in which this evidence has been exploited in the clinic and laboratory. Epidemiology themes dwell on the strong correlation of disease incidence with sexual behaviour of both male and female, sufficient to regard cervical cancer as a type of venereal disease and an equally strong correlation with socio-economic class. Mortality rises when the male partner resides in the lower social classes. Laboratory and clinical studies have defined the tissue at risk and a few studies attempt definition of reasons for such risk. The accent in these studies is on a derangement of the cell filament system seen as grades of unusual keratinization. The vast bulk of laboratory studies is devoted to a definition of the carcinogen. The venereal nature of the epidemiological evidence renders a transmissible agent as most suspect. Viruses have been a popular subject because of this demonstrable capacity to transform cells in vitro and in vivo. Our own studies have concentrated on a component of the sperm as carcinogen or cocarcinogen. A new approach to carcinogenesis, relying on study of energy flow through the cell, is discussed in terms of its close relationship to events in the transforming and transformed cervical cell.

Environmental variables related to cervical cancer

An original study was undertaken to establish an epidemiologic direction for a series of replicates seeking causation of cervical cancer and separating genetic and environmental influences. Results of this first study are sufficiently interesting for a report. 1.1. Patients showed earlier onset of sexual experience by 3 years or longer suggesting a possible reason why in other studies earlier marriage appears to influence onset of cervical carcinoma. In general, controls were more active sexually. The large event of initiation into sexual practice may perhaps subserve causation of cervical cancer if it occurs too early in life, whereas an active sexual life may be compensatory in the opposite direction. A similar result of “haste to begin early … the reproductive phase of biologic destiny” in the lives of cervical cancer patients was described in the study of Jones, MacDonald, and Breslow5, and Wynder and associates15, and by Lombard and Potter8 for early marriage.2.2. The data indicate that miscarriages are not associated with onset of cervical cancer and suggest that multiple induced abortions may possibly be implicated.3.3. Venereal disease, cervicitis, and curettage showed no influence upon onset of cervical cancer.4.4. The role of hormonal imbalance is suggestive but not clearly significant.5.5. Functions associated with menstruation are not related to the onset of the cervical cancer if the menstrual pattern is an index of function.6.6. Parity appears to have no effect upon onset of cervical cancer.7.7. Masturbation appears to have no carcinogenic effect upon the cervix.8.8. Circumcision in coital mates is not significantly different in patients and controls and there is no evidence from the data in groups not religiously biased that circumcision enters into causation of cervical cancer.9.9. No important differences between contraceptive practices of patients and controls were revealed.10.10. There is a higher level of obesity in patients compared to controls but this could be a matter of chance unless confirmed by future data.