Association between human herpesvirus infection and cervical carcinoma: a systematic review and meta-analysis.

BACKGROUND: Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk. METHODS: Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL). RESULTS: Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies. CONCLUSIONS: This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.

Risk of precancerous cervical lesions in women using a hormone-containing intrauterine device and other contraceptives: a register-based cohort study from Denmark.

STUDY QUESTION: Is the risk of high-grade precancerous cervical lesions and/or is the risk of lesion progression increased in users of a hormone-containing intrauterine device (HIUD) compared with users of other contraceptive methods. SUMMARY ANSWER: Women starting use of HIUD had the same subsequent risk of cervical intraepithelial neoplasia 3+ (CIN3+) as copper IUD (CIUD) users, and both groups tended to have lower risks than oral contraceptives (OC) users. WHAT IS KNOWN ALREADY: HIUDs may cause inflammatory and immunosuppressive changes that may potentially affect the risk of persistent human papillomavirus infection and precancerous cervical lesions. STUDY DESIGN, SIZE, DURATION: A Danish population-based cohort study was conducted using register data from 2008 to 2011 on 26-50-year-old users of HIUD (n = 60 551), CIUD (n = 30 303), or OC (n = 165 627). PARTICIPANTS/MATERIALS, SETTING, METHODS: Within each user group, women were divided into two groups; normal cytology or abnormal diagnosis before start of contraceptive use (baseline). Follow-up histology and cytology diagnoses were registered during the 5 years after baseline. Adjusted relative risks (aRR) and 95% CI were calculated for precancerous cervical lesions in HIUD users compared with CIUD and OC users. MAIN RESULTS AND THE ROLE OF CHANCE: Women with normal cytology at baseline: at follow-up HIUD users had the same risk of CIN3 or higher (3+) as CIUD users; aRR 1.08 (95% CI 0.94-1.22). For the HIUD and CIUD groups compared with OCs, the risks of CIN3+ were lower: aRR 0.63 (95% CI 0.57-0.69) and aRR 0.58 (95% CI 0.52-0.65), respectively. The same was observed for CIN2 risks: aRR 0.86 (95% CI 0.76-0.96) and aRR 0.68 (95% CI 0.58-0.79) for HIUD and CIUD groups, respectively. Women with abnormal diagnosis at baseline: a lower progression risk, except for CIN2+ at baseline, was observed in HIUD users compared with OC users. Similar progression risks were found in HIUD and CIUD users. There were no differences between the three contraceptive groups in persistence or regression of present lesions. LIMITATIONS, REASONS FOR CAUTION: We adjusted for age, education, and region of residence as a proxy for socio-economic factors. Data on smoking and sexual behavior were not available thus we cannot exclude some differences between the three user groups. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that women may safely use HIUDs. STUDY FUNDING/COMPETING INTEREST(S): A.P. Møller Foundation for the Advancement of Medical Science, Else and Mogens Wedell-Wedellborgs Fund, Direktør Emil C. Hertz og Hustru Inger Hertz Fund, and the Fund for Development of Evidence Based Medicine in Private Specialized Practices. EL is principle investigator for a study with HPV-test-kits provided by Roche. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Magnitude and associated factors of VIA positive test results for cervical cancer screening among refugee women aged 25-49 years in North Ethiopia.

BACKGROUND: Worldwide cervical cancer is the third most common malignancy in women. It usually arises from the cervical area which is susceptible to Human Papilloma virus induced malignancy changes. In low-resource setting visual inspection with acetic acid (VIA) is an alternative sensitive cervical screening method. Therefore the aim of this study was to assess the magnitude and associated factors of VIA positive test results for Cervical Cancer screening among Eritrean refugee women aged 25-49 years in northern Ethiopia refugee camps. METHODS: A community based cross-sectional study was conducted among 412 Eritrean refugee women aged 25-49 years from august 10 to September 25, 2018. Study subjects were selected by simple random sampling method. Data were collected using pretested structured questioner through Face-to-face interview and cervical examination. Data were coded and entered to Epi info software version 7 and then exported to Statistical package for Social Science (SPSS) version 21 for analysis. Bivariable and multivariable logistic regression analysis was made to test the association between the independent variables and the outcome variable. P-value of less than 0.05 with 95% CI was considered to declare statistical significance. RESULT: In this study the magnitude of VIA positive precancerous cervical lesions was 9% (95% CI: 6.3-11.8%). Previous history of sexually transmitted infections (STI) [AOR (95%CI) = 2.84(1.07-7.53)] and presence of STI during cervical examination [AOR (95%CI) =3.97(1.75-9.00)] were found significantly associated with VIA positive precancerous cervical lesions. CONCLUSIONS: In this study the magnitude of VIA positive precancerous cervical lesions was high. Previous history of sexually transmitted infections (STI) and presence of STI during cervical examination were found associated with VIA positive precancerous cervical lesions. Efforts such as early screening for sexually transmitted disease shall be done to prevent precancerous cervical lesions.

Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease-a 16-year follow-up study.

BACKGROUND: Women treated for high-grade cervical intraepithelial neoplasia (grade 2 or 3) are at elevated risk for developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality, and presence of high-risk human papilloma virus after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure. OBJECTIVE: In this study, we examine the long-term risk of residual/recurrent high-grade cervical intraepithelial neoplasia among women previously treated for cervical intraepithelial neoplasia 2/3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with high-risk human papilloma virus acquisition and/or cervical intraepithelial neoplasia progression), posttreatment presence of high-risk human papilloma virus, and other factors. MATERIALS AND METHODS: This prospective study included 991 women with histopathologically confirmed cervical intraepithelial neoplasia 2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age, and high-risk human papilloma virus status during follow-up, and residual/recurrent high-grade cervical intraepithelial neoplasia was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent high-grade cervical intraepithelial neoplasia was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression. RESULTS: During a median of 10 years and maximum of 16 years of follow-up, 111 patients were diagnosed with residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Women with positive/uncertain margins had a higher risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse than women with negative margins, adjusting for potential confounders (hazard ratio, 2.67; 95% confidence interval, 1.81-3.93). The risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse varied by anatomical localization of the margins (endocervical: hazard ratio, 2.72; 95% confidence interval, 1.67-4.41) and both endo- and ectocervical (hazard ratio, 4.98; 95% confidence interval, 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive or uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder, and/or organ transplant) was also a significant independent predictor of residual/recurrent high-grade cervical intraepithelial neoplasia or worse. In women with positive high-risk human papilloma virus findings during follow-up, the hazard ratio of positive/uncertain margins for recurrent/residual high-grade cervical intraepithelial neoplasia or worse increased significantly compared to that in women with positive high-risk human papilloma virus findings but negative margins. CONCLUSION: Patients with incompletely excised cervical intraepithelial neoplasia 2/3 are at increased risk for residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Margin status combined with high-risk human papilloma virus results and consideration of comorbidity may increase the accuracy for predicting treatment failure.

Precancerous cervical lesions and associated factors among women on antiretroviral therapy at Dukem Health Center, Central Ethiopia: A cross-sectional study.

Background and Aims: Cervical cancer is a global public health problem and the second most common cancer which leads to morbidity and mortality among women in developing countries like Ethiopia. In Ethiopia, annually 6294 new cervical cancer cases and 4884 deaths are estimated in 2018 alone. This study aimed to assess the prevalence and associated factors of precancerous cervical lesions among women on antiretroviral therapy (ART) at Dukem Health Center, Central Ethiopia. Methods: An institution-based cross-sectional study was carried out among randomly selected 257 women receiving ART at Dukem Health Center. Data were collected using a pretested structured questionnaire, medical record review, and visual inspection with acetic acid. Collected data were entered into Epi-info 7.4 and exported to SPSS version 26 for analysis. The prevalence of precancerous cervical lesions and the characteristics of study participants were identified. Utilizing both binary and multivariable logistic regression models, the existence and degree of association with precancerous cervical lesions were determined with a p value < 0.05 and a 95% confidence interval. Results: The prevalence of precancerous cervical lesions was 16% (95% CI: 11.7-20.6). Significant association was found between precancerous cervical lesions and a history of STIs (AOR = 4.30, 95% CI: 1.48-12.49), oral contraceptive use (AOR = 6.56, 95% CI: 2.10-20.50), having multiple lifetime sexual partners (AOR = 2.53: 95% CI: 1.05-6.10), and a recent CD4 count of less than 200 cells/mm3 (AOR: 11.33, 95% CI: 2.88-24.58). Conclusion: In the study area, the prevalence of precancerous cervical lesions was relatively high. Therefore, concerned bodies are recommended to increase awareness of the prevention of sexually transmitted diseases and limit sexual partners.

Cataloging circulating CD3+CD56+ NKT-like cells through a series of stimulating (NKG2D and DNAM-1) and inhibitory (PD-1, TIGIT, and Tim-3) immune checkpoint receptors in women diagnosed with precancerous cervical lesions or invasive cervical carcinoma.

Persistent human papillomavirus infection is associated with the development of premalignant lesions that can eventually lead to cervical cancer. In this study, we evaluated the expression of activating (NKG2D, DNAM-1) and inhibitory immune checkpoints receptors (PD-1, TIGIT, and Tim-3) in peripheral blood NKT-like (CD3+CD56+) lymphocytes from patients with cervical carcinoma (CC, n = 19), high-grade lesions (HG, n = 8), low-grade lesions (LG, n = 19) and healthy donors (HD, n = 17) using multiparametric flow cytometry. Dimensional data analysis showed four clusters within the CD3+CD56+ cells with different patterns of receptor expression. We observed upregulation of CD16 in CC and HG patients in one of the clusters. In another, TIGIT was upregulated, while DNAM-1 was downregulated. Throughout manual gating, we observed that NKT-like cells expressing activating receptors also co-express inhibitory receptors (PD-1 and TIGIT), which can affect the activation of these cells. A deeper characterization of the functional state of the cells may help to clarify their role in cervical cancer, as will the characterization of the NKT-like cells as cytotoxic CD8+ T cells or members of type I or type II NKT cells.

Cervical Precancerous Lesions and Associated Factors Among Women Screened in Two Hospitals in the City of Douala, Cameroon.

INTRODUCTION: Cervical cancer remains the second leading cause of death among women in Cameroon despite the new strategies put in place. This study was conducted in order to determine the prevalence of precancerous cervical lesions and its associated factors in Douala (Cameroon). METHODS:  A cross-sectional study was conducted over a period of nine months in two hospitals of the city of Douala, Cameroon (Laquintinie Hospital and Gyneco-Ostetric and Pediatric Hospital). Cervico-vaginal and endocervical samples were taken from women attending the above-mentioned hospitals in order to identify and characterize precancerous lesions by cytological examination and to genotype for human papillomavirus (HPV) using the Abbott RealTime High-Risk (HR) HPV kit. Data of sociodemographic characteristics, clinical history, and knowledge about cervical cancer were collected using a questionnaire. RESULTS: Of the 196 women included in this study, 17% had precancerous lesions, including 1.53% for atypical glandular cells (AGC), 4.53% for atypical squamous cells (ASC), 4.53% for low-grade squamous intraepithelial lesion (LSIL), 5.61% for high-grade squamous intraepithelial lesion (HSIL), 0.51% for atypical squamous cells of undetermined significance (ASC-US), and 0.51% for atypical squamous cells cannot exclude HSIL (ASC-H). In addition, the prevalence of HPV infection was 18%, of which 2% was for HPV 16, 2% for HPV 18, and 14% for undetermined HPV. A positive association was recorded between the occurrence of precancerous lesions and HPV infection (P=0.01), age, and school level. Moreover, the occurrence of precancerous lesions was positively associated with the participants' level of knowledge (P=0.01). DISCUSSION: Precancerous lesions were predominantly HSIL, and the factor most associated with these lesions was HPV infection. CONCLUSION: This study demonstrates that diagnosis is made at a relatively late stage due to a low level of knowledge about cervical cancer in the population.

Application of EfficientNet-B0 and GRU-based deep learning on classifying the colposcopy diagnosis of precancerous cervical lesions.

BACKGROUND: Colposcopy is indispensable for the diagnosis of cervical lesions. However, its diagnosis accuracy for high-grade squamous intraepithelial lesion (HSIL) is at about 50%, and the accuracy is largely dependent on the skill and experience of colposcopists. The advancement in computational power made it possible for the application of artificial intelligence (AI) to clinical problems. Here, we explored the feasibility and accuracy of the application of AI on precancerous and cancerous cervical colposcopic image recognition and classification. METHODS: The images were collected from 6002 colposcopy examinations of normal control, low-grade squamous intraepithelial lesion (LSIL), and HSIL. For each patient, the original, Schiller test, and acetic-acid images were all collected. We built a new neural network classification model based on the hybrid algorithm. EfficientNet-b0 was used as the backbone network for the image feature extraction, and GRU(Gate Recurrent Unit)was applied for feature fusion of the three modes examinations (original, acetic acid, and Schiller test). RESULTS: The connected network classifier achieved an accuracy of 90.61% in distinguishing HSIL from normal and LSIL. Furthermore, the model was applied to "Trichotomy", which reached an accuracy of 91.18% in distinguishing the HSIL, LSIL and normal control at the same time. CONCLUSION: Our results revealed that as shown by the high accuracy of AI in the classification of colposcopic images, AI exhibited great potential to be an effective tool for the accurate diagnosis of cervical disease and for early therapeutic intervention in cervical precancer.

Prevalence of Precancerous Cervical Lesions among Nonvaccinated Kazakhstani Women: The National Tertiary Care Hospital Screening Data (2018).

OBJECTIVE: At the present time, cervical cancer remains the fourth most prevalent cancer among women worldwide. Most cervical cancer cases are attributed to high-risk human papillomavirus (HPV) infection. Because the natural history of cervical cancer takes decades, the disease could be prevented if premalignant conditions are identified and appropriately managed. The aim of this study is to identify the prevalence of precancerous lesions among non-vaccinated women attending the national tertiary care hospital in Kazakhstan. METHODS: This was a retrospective study of the cervical cancer screening database (2018) from the national tertiary care hospital in Kazakhstan. Records of 6682 patients, who had cervical cytology tests by Papanicolaou (Pap test), were analyzed. Out of the revised cases, 249 patients had abnormal cervical cytology reports. The Pap test was performed using liquid-based cytology (LBC). The data were analyzed using the statistical software STATA 16. A p-value of less than 0.05 was considered statistically significant. RESULTS: In this retrospective analysis of 6682 patients' records, we found 3.73% (249 patients) out of all Pap tests performed in 2018 were abnormal. The prevalence of high-grade squamous intraepithelial lesion (HSIL) was high at 19.28%, and the proportion of atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells (ASCs-H) was 18.47%, while low-grade squamous intraepithelial lesion (LSIL) were identified in 62.25% of the cases. Almost 25% of the women included in the study had concurrent lower and upper genital tract infections. CONCLUSION: Although the overall rate of abnormal Pap test results was not high, the study shows the elevated prevalence of HSIL. It calls the attention of local policymakers and gynecology specialists and requires immediate actions to improve the prophylactic measures to decrease morbidity and mortality from cervical cancer in Kazakhstan.

Evaluations of the 2019 Annual Statistics Under the Cervical Cytology Quality Assurance Agreement: 2019 Annual Statistics for Cervical Cytology from 15608413 Women.

Background: Cervical cancer screening, which was introduced into the programme of medical care covered by statutory health insurance in Germany in 1971 and has since been constantly updated through quality assurance measures, was fundamentally revised and developed in 2008 through the Cervical Cytology Quality Assurance Agreement pursuant to Section 135(2) of the German Social Code Book V [SGB V]. Since 2015 it has been mandatory for cytology facilities to record annual statistics based on the Munich Nomenclature III. The aim of this article is to present the results of the annual statistics for 2019, which was the last year before the introduction of the cervical cancer screening programme in accordance with the Federal Joint Committee's guideline on organised cancer screening programmes 1 . Materials and Methods: The annual statistics of the laboratories, including histology analyses performed up until 30 June the following year, are reported to the Regional Associations of Statutory Health Insurance Physicians. The laboratories receive benchmark reports from their Regional Associations of Statutory Health Insurance Physicians, and these statistics are transmitted anonymously to the National Association of Statutory Health Insurance Physicians (KBV). Results: In 2019, 17609082 smears from 15608413 women were examined in Germany. Of these smears, 97.49% were normal and 2.51% showed atypical or suspicious changes, consisting mostly of minor squamous epithelial changes in groups II-p (0.81%) and IIID1 (0.735%).Histology specimens are available for "Dysplasia findings with higher probability of regression" in group IIID1 (4.89% of initial IIID1 cytology findings), group IIID2 (18.60%), "unclear or doubtful findings" in group III-p to x (20.7%), and "immediate precursors to cervical carcinoma" in group IV (83.1%) and group V (77.19%).In the cytology findings for group IVa-p, which corresponds to CIN 3 target lesions, the cytology correlated with the histology finding in 80.48% of cases.Lesions found in 2019: 23463 CIN 3 lesions, 668 adenocarcinomas in situ, 3891 malignant tumours, including 2342 cervical carcinomas of which 1743 were squamous cell carcinomas and 599 were cervical adenocarcinomas (25.57%); 1549 endometrial carcinomas and other malignancies. Inference/Conclusion: The data demonstrate the good practicability of cervical cancer screening in 2019. Higher grade lesions were reliably clarified histologically.

Effectiveness and Safety of Therapeutic Vaccines for Precancerous Cervical Lesions: A Systematic Review and Meta-Analysis.

Objective: This study systematically evaluated the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions, providing evidence for future research. Methods: We systematically searched the literature in 10 databases from inception to February 18, 2021. Studies on the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions were included. Then, we calculated the overall incidence rates of four outcomes, for which we used the risk ratio (RR) and 95% confidence interval (95% CI) to describe the effects of high-grade squamous intraepithelial lesions (HSILs) on recurrence. Results: A total of 39 studies were included, all reported in English, published from 1989 to 2021 in 16 countries. The studies covered 22,865 women aged 15-65 years, with a total of 5,794 vaccinated, and 21 vaccines were divided into six types. Meta-analysis showed that the overall incidence rate of HSIL regression in vaccine therapies was 62.48% [95% CI (42.80, 80.41)], with the highest rate being 72.32% for viral vector vaccines [95% CI (29.33, 99.51)]. Similarly, the overall incidence rates of HPV and HPV16/18 clearance by vaccines were 48.59% [95% CI (32.68, 64.64)] and 47.37% [95% CI (38.00, 56.81)], respectively, with the highest rates being 68.18% [95% CI (45.13, 86.14)] for bacterial vector vaccines and 55.14% [95% CI (42.31, 67.66)] for DNA-based vaccines. In addition, a comprehensive analysis indicated that virus-like particle vaccines after conization reduced the risk of HSIL recurrence with statistical significance compared to conization alone [RR = 0.46; 95% CI (0.29, 0.74)]. Regarding safety, only four studies reported a few severe adverse events, indicating that vaccines for precancerous cervical lesions are generally safe. Conclusion: Virus-like particle vaccines as an adjuvant immunotherapy for conization can significantly reduce the risk of HSIL recurrence. Most therapeutic vaccines have direct therapeutic effects on precancerous lesions, and the effectiveness in HSIL regression, clearance of HPV, and clearance of HPV16/18 is great with good safety. That is, therapeutic vaccines have good development potential and are worthy of further research. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021275452.

Prevalence and risk factors associated with precancerous cervical lesions among women in two cities in Cameroon.

Introduction: cervical cancer is the fourth commonest cancer of women world-wide with increasing incidence in developing countries. This study determined the prevalence and assessed risk factors associated with precancerous cervical lesions among women in Cameroon. Methods: this cross-sectional study enrolled 925 women participants of a screening campaign for precancerous cervical lesions from June to November 2018 in the selected hospitals. A convenience sampling technique was used and socio-demographic, sexual and reproductive data collected from consented participants by means of self-administered questionnaire. During the gynaecologic examination, a cervical smear was collected, stained by the Papanicolaou staining technique and the results classified according to the Bethesda 2014 guidelines. Frequency, percentage, Chi square and regression analysis were conducted using SPSS version 20 and p-value considered at 0.05. Results: of the 925 participants aged 25-65 years (mean 40.2±10.2 SD), 113 (12.2%) had the lesions among whom 9 (7.9%) had atypical squamous cells of undetermined significance, 75 (66.4 %) had Low-grade squamous intraepithelial lesion and 29 (25.7%) had high-grade squamous intraepithelial lesion. Factors associated with the lesions were: age 1.85 [1.42-2.41; p= 0.001] and parity [OR= 1.46; 95% CI: 1.30-1.89; P= 0.004]. Conclusion: the prevalence of precancerous lesions was 12.2%. Age, parity were significant risk factors. Regular screening targeting the population at risk in this study becomes a priority.

Prevalence and Associated Factors of Precancerous Cervical Lesions among Women in Ethiopia: A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical cancer remains the most common cancer of women worldwide. Its burden is more serious in developing countries. It is also the second common cancer deaths of women in Ethiopia followed by breast cancer. The aim of this study was to determine the pooled prevalence and associated factors of precancerous cervical lesions among women in Ethiopia. METHODS: We systematically searched published and unpublished articles reported from 2010 to 2019 using a comprehensive search of electronic databases including PubMed and Google scholar for grey literature from August 1 to September 1, 2019. The methodological qualities of included studies were evaluated using Joanna Briggs Institute meta-analysis of Statistics Assessment. The pooled prevalence estimate was calculated using MedCalc software-version 19.0.7, and the pooled odd ratios for predictors was calculated using RevMan software version 5.3. RESULTS: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was 13.4% (95% CI:10.63% 16.37%). Statistically significant heterogeneity between studies was detected (I2=83.1%, P < 0.001). Among all measured associated factors: numbers of women life time sexual partners > 1, OR=2.5 (95% CI:3.70,4.76), being HIV positive women, OR=2.4 (95% CI:1.33,4.61) and women having history of STI, OR=2.0 (95% CI:1.02,3.87) had statistically significant association with precancerous cervical lesions among women in Ethiopia. CONCLUSION: The pooled prevalence of precancerous cervical lesions among women in Ethiopia was high as compared to the 5-year worldwide cervical cancer prevalence. Women having more than one life time sexual partners, being HIV positive women and women having history of STI had a statistically significant association with precancerous cervical lesions.

Association Between MALAT1 and THRIL Polymorphisms and Precancerous Cervical Lesions.

BACKGROUND: The occurrence of cervical cancer is a complex process, for which human papillomavirus (HPV) infection is a risk factor, although not all women infected with HPV will develop the disease. Knockout of mammalian lung metastasis associated transcript 1 (MALAT1) is associated with increased risk for several cancer types, whereas the long non-coding RNA (lncRNA) THRIL is essential for induction of tumor necrosis factor-α expression, which plays important roles in HPV infection. MATERIALS AND METHODS: To investigate the effects of polymorphisms in the lncRNAs MALAT1 and THRIL on the susceptibility to precancerous cervical lesions, 12 single nucleotide polymorphisms (SNPs) were analyzed from 164 cervical precancerous lesion cases and 428 controls. Gene-gene and gene-environment interactions and haplotype associations were also evaluated. RESULTS: We found a significantly decreased risk of precancerous cervical lesions for the THRIL rs7133268 AG genotype (odds ratio adjusted = 0.63, 95% confidence interval: 0.42-0.94, p = 0.025). Multifactor dimensionality reduction analysis identified a significant two-locus interaction model involved in HPV infection and THRIL rs7133268 (training balanced accuracy = 0.6957, testing balanced accuracy = 0.6948, cross-validation consistency = 10/10, p = 0.0046). Other SNPs, including the two identified for MALAT1, were not significantly related to the risk of precancerous cervical lesions. CONCLUSION: Our results suggest that the rs7133268 polymorphism of the lncRNA THRIL gene can reduce the genetic susceptibility of precancerous cervical lesions and in turn reduce the risk of HPV infection.

Association of HLA-G 3' UTR polymorphism and expression with the progression of cervical lesions in human papillomavirus 18 infections.

BACKGROUND: Human leukocyte antigen (HLA)-G is an immune checkpoint molecule, which expression in cervical cancer cells enables them to escape immunosurveillance. To date, limited information has been published on the association of HLA-G genetic background in malignant cells with levels of HLA-G expression and the clinical outcome of patients. METHODS: We investigated the influence of the HLA-G 14 bp In/Del (rs66554220) and + 3142C/G (rs1063320) polymorphisms in 130 cases of HPV16 infection, 130 cases of HPV18 infection and 185 age-matched, unrelated, HPV-negative, and cytologically normal Chinese Han women. Case-matched cervical biopsy tissues were evaluated by immunohistochemistry. RESULTS: Our findings show that the frequency of alleles, 14 bp In (38.5% vs 29.2%, OR = 1.52, P < 0.05) and + 3142G (72.7% vs 57.0%, OR = 2.01, P < 0.05), were significantly increased in the HPV18-infected group compared with the control group. The HLA-G polymorphisms (alleles 14 bp In and + 3142G) are also associated with the progression of HPV18-related cervical lesions. Moreover, HLA-G expression increased from CIN1 to CIN2/3 lesions and was highest in patients with adenocarcinoma; however, a significant association between these characteristics and the HLA-G polymorphisms was not observed. CONCLUSION: Our results support that the HLA-G 14 bp In and + 3142G alleles are risk factors for HPV18 infections and influence the progression of HPV18-related cervical lesions. This suggests that HLA-G-driven immune mechanisms play an important role in cervical carcinogenesis.

Clinical significance of HPV-DNA testing for precancerous cervical lesions.

Cervical screening by using cytology was proven efficient in reducing the mortality secondary to cervical cancer, but this method has limitations. High risk HPV infection is essential for cervical cancer development so HPV testing is a new tool used for screening patients for cervical neoplasia. HPV testing was proven most useful for women over 30 years old, in cases in which cytology identified ASC-US and after treatment for CIN. This article outlines the clinical significance of HPV-DNA testing for precancerous cervical lesions and the evidence that stands behind these recommendations.

Impact of Highly Active Antiretroviral Therapy on the Natural History of Cervical Precancerous Lesions: A 17-Year Institutional Longitudinal Cohort Study.

We performed an observational cohort study in order to assess the correlation between precancerous cervical lesions (cervical intraepithelial neoplasia [CIN]) and immunological state in human immunodeficiency virus (HIV)-positive women treated by highly active antiretroviral therapy (HAART). We analyzed 194 HIV-infected women referred to the Parma-Universitary Hospital for early detection of human papilloma virus-induced CINs. We analyzed cytology, colposcopy, and CIN degree according to HAART: group A untreated and group B treated. We compared the CD4+ count and viral load at the time of CIN onset and the time interval between diagnosis of HIV and the onset of CIN. Group A and group B showed homogeneous results for general features, CD4+ count, viral load, and Papanicolaou test features. Differences were not found in terms of histology and CD4+ value, viral load count, pharmacological treatment, years since the diagnosis of HIV, age, smoking, sexual promiscuity, previous intravenous narcotics abuse, prostitution, sexually transmitted diseases, ethnicity, and age at diagnosis. Histology and the clinical stage of HIV showed significant concordances between the high degree of cervical dysplasia and advanced stage of HIV disease.

Prospective cohort study on the value of high-risk human papillomavirus viral load and subtype tests in predicting cervical intraepithelial neoplasia / 中国肿瘤临床

Objective:To evaluate high-risk human papillomavirus (hrHPV) genotyping and viral load in predicting CIN (cervical intraepi-thelial neoplasia (CIN) grade 2 or worse in a Chinese rural area population with limited health resources. Methods:We performed a population-based prospective study and enrolled 2,257 women aged 35 to 64 years from three rural screening sites of Jiangxi prov-ince. We conducted a hybrid capture (HC-2) assay to predict viral load. A HC-2 relative light unit (RLU) threshold of 10 was set to differ-entiate samples between low (<10) and high (≥10) viral loads. We also carried out a HybriMax test to detect different hrHPV geno-types in the samples. Women exhibiting positive HC-2 or HybriMax results underwent colposcopy and colposcopically directed biopsy. Women with negative or positive hrHPV test results but with normal biopsy or CIN1 were followed-up for 24 months without interven-tion (n=2,211). We used histopathological findings as outcome. Results:Of the 2,211 women, 1,636 provided complete follow-up data. Of the 132 women with a high viral load, 4 (3.03%) developed CIN2+in the same period. The relative risk (RR) of CIN2+for HC-2 posi-tivity at baseline was 42.24 (95%CI=4.76-375.2). Of the 159 women who were positive for HPV16 or HPV18 upon screening, 4 (2.52%) progressed to CIN2+(RR=33.06, 95%CI=3.72-293.9). The 2-year cumulative incidence rates of CIN2+did not significantly differ be-tween the high viral load group and the HPV16/18 group. Conclusion:The risks of CIN2+progression were higher among women with a high viral load or HPV16/18 positivity than among women with negative hrHPV. Increasing the HC-2 cut-off value to 10 RLU or using HPV16/18 positivity may be similarly used to triage hrHPV-positive women for immediate colposcopy and comprehensive follow-up.Both approaches were equally predictive of the CIN2+risk in rural area. Increasing the HC-2 cut-off value to 10 RLU may also help allo-cate health resources effectively.