Influence of Demographic and Reproductive Factors on Cervical Pre-Cancer and Cancer in Bangladesh

Background: In Bangladesh, cervical cancer (CC) is the 2nd most common cancer with estimated 8068 new cases and 5,214 deaths every year. It is also revealed that different socio-demographic factors have association with CC. This study was performed to evaluate the colposcopy outcomes and the association of different demographic and reproductive risk factors with cervical pre-cancer and cancer. Methods: This retrospective cross-sectional study was carried out at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) between January 2010 and December 2016. Results: A total 16147 women attended the colposcopy clinic of BSMMU with VIA positive reports. Among them, 65.73% women were referred from different VIA centers of Dhaka district. Mean age of marriage of the subjects was 16. 93 (± 1) and mean age of 1st delivery was 18.45 years (± 4.10). Almost three-fourth of them were married before 18 years and had their 1st delivery by 20 years. Colposcopy examination of the VIA positive women revealed that 36.7% had CINI, 10.6% had CINII/ III and 7.1% had carcinoma of cervix. Considering CIN as disease the Sensitivity, Specificity, PPV and NPV of colposcopy were found 99.7%, 75.3%, 70.3% and 99.8% respectively. On other hand considering CIN2+ as disease the Sensitivity, Specificity, PPV and NPV of colposcopy were found 73.8%, 92.7%, 64.4% and 95.2% respectively. Statistical analysis revealed that higher age (p=0.000), lower level of education (p=0.007), lower socioeconomic status (p=0.014), higher parity (p=0.001) had individual influence on cervical pre-cancer and cancer. Conclusions: This study indicated higher age, low level of education, lower socio-economic condition and higher parity as most important socio-demographic factors for developing cervical pre-cancer and cancer in Bangladesh.     

Cervical Cancer: Screening and Prevention

Cancer of the cervix is the second most common life-threatening cancer among women worldwide and bothincidence and mortality rates are likely to be underestimated in developing countries. HPV high risk strains play atleast the major if not an absolutely necessary role in the etiology. The concept of cervical intraepithelial neoplasia(CIN) was introduced in 1968 as an equivalent to the term dysplasia, which means abnormal maturation. Cervicalcancer progresses slowly from preinvasive CIN to invasive cancer and therefore screening for dysplasia is an importantpublic health effort worldwide, given the accessibility of the primary organ site, the acceptability of current screeningmethods, and the long preinvasive period in which to detect disease and successfully intervene. It is widely acceptedthat detection and treatment of HPV-related dysplastic epithelial change in the form of CIN-2 and CIN-3 canprevent the development of invasive cervical cancer in individual patients. The mainstay of screening programs hasbeen the Pap smear, introduced originally by George Papanicolaou in 1941. However, considerable numbers of falsenegativePap smears may occur with the traditional Pap technique, mostly due to sampling error. More recently, theuse of liquid-based technologies such as ThinPrep and AutoCyte Prep have gained popularity, in part because ofevidence suggesting reduction in the incidence of inadequate smears. It is also hoped that the ability to identifypatients with oncogenic HPV types will lead to improved detection in women more likely to have squamousintraepithelial lesions. Hybrid Capture 2 is the latest refinement of HPV tests and has been described as havingenhanced sensitivity. HPV DNA testing can be used as an adjunct to cytology in routine cervical disease screeningprograms. Establishment of the link between HPV and cervical cancer has further provided the impetus for researchinto prophylactic vaccination against the most common HPV types associated with the disease, HPV 16 and 18.Initial studies have provided evidence that L1 virus-like particle vaccines against HPV types (as monovalent, bivalent,or quadrivalent vaccines) prevent at least 90% of incident and persistent infections and their associated precursorsof cervical cancer. This vaccine has sustained long-term vaccine efficacy against incident and persistent infectionsand in the long term should provide an answer to the cervical cancer problem. For the vast majority of women whohave already been infected, however, continued screening and resection need to be emphasized.     

Reasons for Variation in Sensitivity and Specificity of Visual Inspection with Acetic Acid (VIA) for the Detection of Pre-Cancer and Cancer Lesions of Uterine Cervix

Alternative strategies such as visual inspection of cervix with acetic acid, are real time, economical and easilyimplemented methods for cervical cancer screening. However, variable sensitivity and specificity have beenobserved in various community based studies. The possible reasons could include variation in man power training,light source used for visualization, and preparation of diluted (4-5%) acetic acid and its storage. A standardizedprotocol for training, teaching material (easy to understand in the local language) for trainees, supervision andreinforcement by intermittent and supplementary training to check the quality of their observation, a standardprotocol for preparation dilute acetic acid and its storage and a standard good light source (equivalent to daylight) are needed to minimize the variation in sensitivity and specificity of VIA in community settings.     

Comparison between Visual Inspection of Cervix and Cytology Based Screening Procedures in Bangladesh

Background: Cervical cancer continues to be a major problem in Bangladesh with approximately 18,000 newcases annually of which over 10,000 women die from it. Visual inspection of the cervix after 3-5% acetic acid(VIA) application is a simple and easy to learn method for cervical cancer screening, although cytology-basedscreening is more often applied in developed countries where it has successfully reduced the prevalence of cervicalcancer. Objective: To compare the efficacy of VIA and cytology-based primary methods for cervical cancerscreening in Bangladesh. Materials and Methods: This hospital based comparative study was conducted at theVIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) from October2008 to October 2010. Results: Among 650 women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalitiesin their Pap smear reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4 (0.6%)had cervical cancer. The gold standard histology findings proved 20 women had CIN I, 14 had CIN II/II and 4had cervical cancer. Among the 38 histology diagnosed abnormalities, VIA test could identify 30 abnormalitiesincluding two cervical cancers. However, Pap smear could detect only 8 cases of histological abnormalities (2low grade and 6 had high grade lesion) and it missed all the cervical cancer cases. The sensitivity and specificityof VIA were 88.9% and 52.1%. The positive predictive value (PPV) and negative predictive value (NPV) were41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV and NPV of Pap smear were 33.3%,95.8%, 75.0% and 79.3%, respectively. Conclusions: VIA test should be used as the primary screening tool evenwith its low sensitivity and specificity in low resource countries like Bangladesh. False positive results may begreater, but overtreatment can be minimized by colposcopy evaluation of the VIA positive women.     

Cervical Cancer Prevention and Early Detection; The Role of Nurse and Midwives

Worldwide 31% of cancers in women are in the breast or uterine cervix. Cancer of the uterine cervix is one of the ‍leading causes of cancer death among women. The estimated new cancer cervix cases per year is 500.000 of which ‍79% occur in the developing countries, where it is consistently the leading cancer and there are in excess of 233.000 ‍deaths from the disease. The major risk factors for cervical cancer include early age at first intercourse, multiple ‍sexual partners, low socioeconomic status, HSV, HPV infection, cigarette smoking and extended use of oral ‍contraceptives. Well organized and applied public education and mass screening programmes can substantially ‍reduce the mortality from cervical cancer and the incidence of invasive disease in the population. Women who are ‍health conscious are more likely to have used screening services (mammogram, pap-smear test) and performed ‍breast-self examination and genital hygiene. There are both opportunities and burdens for nurses and midwives ‍working in primary health care settings. This is a prime example of a role of public education in cancer prevention ‍with reference to population-based cancer screening programs. ‍     

Mapping HPV Vaccination and Cervical Cancer Screening Practice in the Pacific Region-Strengthening National and Regional Cervical Cancer Prevention

Objective : To provide background information for strengthening cervical cancer prevention in the Pacificby mapping current human papillomavirus (HPV) vaccination and cervical cancer screening practices, as wellas intent and barriers to the introduction and maintenance of national HPV vaccination programmes in theregion. Materials and Methods: A cross-sectional questionnaire-based survey among ministry of health officialsfrom 21 Pacific Island countries and territories (n=21). Results: Cervical cancer prevention was rated as highlyimportant, but implementation of prevention programs were insufficient, with only two of 21 countries andterritories having achieved coverage of cervical cancer screening above 40%. Ten of 21 countries and territorieshad included HPV vaccination in their immunization schedule, but only two countries reported coverage of HPVvaccination above 60% among the targeted population. Key barriers to the introduction and continuation ofHPV vaccination were reported to be: (i) Lack of sustainable financing for HPV vaccine programs; (ii) Lackof visible government endorsement; (iii) Critical public perception of the value and safety of the HPV vaccine;and (iv) Lack of clear guidelines and policies for HPV vaccination. Conclusion: Current practices to preventcervical cancer in the Pacific Region do not match the high burden of disease from cervical cancer. A regionalapproach, including reducing vaccine prices by bulk purchase of vaccine, technical support for implementationof prevention programs, operational research and advocacy could strengthen political momentum for cervicalcancer prevention and avoid risking the lives of many women in the Pacific.     

Cervical Cancer Prevention Through HPV Vaccination in Low- and Middle-Income Countries in Asia

Cervical cancer is ranked the first or second most common cancer in women of low- and middle-income countries (LMICs) in Asia. Cervical cancer is almost exclusively caused by human papillomavirus (HPV), and majority of the cases can be prevented with the use of HPV vaccines. The HPV vaccines have demonstrated high vaccine efficacies against HPV infection and cervical cancer precursors in clinical and post-marketing studies, and are in use in most high-income countries. However, their use in LMICs are limited mainly due to the high costs and logistics in delivering multiple doses of the vaccine. Other issues such as the safety of the vaccines, social and cultural factors, as well as poor knowledge and awareness of the virus have also contributed to the low uptake of the vaccine. This mini-review focuses on the need for HPV vaccine implementation in Asia given the substantial disease burden and underuse of HPV vaccines in LMICs in this region. In addition, the progress towards HPV vaccine introduction, and barriers preventing further rollout of these essential, life-saving vaccines are also discussed in this article.     

The Breast and Cervical Cancer Prevention and Treatment Act in Georgia

BACKGROUND:

Implementation of the Breast and Cervical Cancer Prevention and Treatment Act of 2000 (BCCPTA) allowed states to extend Medicaid to any woman aged <65 without insurance screened and found to need treatment either for breast or cervical cancer or for a precancerous cervical condition through the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) or in Georgia, other provider sites.

METHODS:

The authors used linked Georgia Comprehensive Cancer Registry (GCCR) and Medicaid data to test the: 1) likelihood of Medicaid enrollment in a given month and 2) time‐to‐enrollment (months) for those eventually enrolling. The authors used difference‐in‐differences analysis to estimate the effects of BCCPTA for breast or cervical cancer cases relative to a control group of women with other cancers. The authors controlled for sociodemographics, stage at diagnosis, year of diagnosis, and county level factors related to insurance levels in the area.

RESULTS:

Compared with the control cancer group, the hazard ratio of Medicaid enrollment for women with breast and cervical cancers increased post‐ vs pre‐BCCPTA implementation. The estimated effect of this increase was that out of every 1000 women with breast cancer, BCCPTA led to 1.7 more (from 2.8 to 4.5 per month) enrolling in Medicaid. The results for women with local or later stages of cervical cancer indicated that of 1000 women with these cancers, the number enrolling in a given month increased by 3.4 due to BCCPTA. Results on time‐to‐enrollment indicated that the time between cancer diagnosis and enrollment was shortened by 7 to 8 months.

CONCLUSIONS:

The Georgia Medicaid program, in response to national legislation, increased the probability of women enrolling in Medicaid earlier and in turn, likely increased their cancer treatment options. Cancer 2009. © 2009 American Cancer Society.     

Role of Cytokines in Genesis,Progression and Prognosis of Cervical Cancer

Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiplesmall molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism,was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible tounravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines,monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancerevery year this cancer is a major cause of mortality and morbidity the world over, particularly in the developingcountries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which ispersistent, particularly in those with a defective immune system. Although preventable, the mere magnitudeof prevalence of HPV in the world population makes it a dominating current health hazard. The discoveryof cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them asbiomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesisand progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, andnow with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated inall anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokineresearch in cervical neoplasia.     

HPV检测在农村宫颈癌筛查中的作用

[目的]了解HPV检测在辽宁省沈阳市苏家屯地区农村妇女宫颈癌筛查过程中的作用,为宫颈癌筛查提供科学依据.[方法]对2014～2015年间自愿接受宫颈癌筛查的35～64岁农村常住妇女,进行调查、取样和HPV检测.[结果]对10 000名35～64岁妇女进行宫颈癌筛查,发现宫颈癌癌前病变80人(其中CIN1为36人,CIN2为30人,CIN3为14人),宫颈癌3人.高危型HPV阳性共1209人,高危型HPV阳性感染率随年龄的升高而升高.HPV的感染率随着病变程度加重而升高;宫颈上皮内瘤变和宫颈癌组HPV 16型的比例显著性高于其他组.[结论] HPV检测在宫颈癌的筛查过程中对提高早诊率具有重要的意义.     

Review of the Cervical Cancer Burden and Population-Based Cervical Cancer Screening in China

Cervical cancer continues to be a serious public health problem in the developing world, including China. Because of its large population with geographical and socioeconomic inequities, China has a high burden of cervical cancer and important disparities among different regions. In this review, we first present an overview of the cervical cancer incidence and mortality over time, and focus on diversity and disparity in access to care for various subpopulations across geographical regions and socioeconomic strata in China. Then, we describe population-based cervical cancer screening in China, and in particular implementation of the National Cervical Cancer Screening Program in Rural Areas (NACCSPRA) and the challenges that this program faces. These include low screening coverage, shortage of qualified health care personnel and limited funds. To improve prevention of cervical cancer and obtain better cancer outcomes, the Chinese government needs to urgently consider the following key factors: reducing disparities in health care access, collecting accurate and broadly representative data in cancer registries, expanding target population size and increasing allocation of government funding for training of personnel, improving health education for women, enhancing quality control of screening services and improving a system to increase follow up for women with positive results.     

HPV Vaccination for Cervical Cancer Prevention is not Cost-Effective in Japan

Background: Our study objectives were to evaluate the medical economics of cervical cancer prevention and thereby contribute to cancer care policy decisions in Japan. Methods: Model creation: we created presenceabsence models for prevention by designating human papillomavirus (HPV) vaccination for primary prevention of cervical cancer. Cost classification and cost estimates: we divided the costs of cancer care into seven categories (prevention, mass-screening, curative treatment, palliative care, indirect, non-medical, and psychosocial cost)and estimated costs for each model. Cost-benefit analyses: we performed cost-benefit analyses for Japan as a whole. Results: HPV vaccination was estimated to cost $291.5 million, cervical cancer screening $76.0 million and curative treatment $12.0 million. The loss due to death was $251.0 million and the net benefit was -$128.5 million (negative). Conclusion: Cervical cancer prevention was not found to be cost-effective in Japan. While few cost-benefit analyses have been reported in the field of cancer care, these would be essential for Japanesepolicy determination.     

Innovations in HPV Vaccination and Roles of Nurses in Cervical Cancer Prevention

The human papilloma virus (HPV) is the main aetiological agent for cervical cancer, one of the most frequentcancers observed in women throughout the world. There are effective programs for reducing the incidence ofcervical cancer with HPV vaccination. The objective of this study was to discuss the applicability of the HPVvaccination and the role of nurses in prevention of cervical cancer. Use of bivalent and quadrivalent vaccineshas been initiated against the types of HPV which are the primary cause of cancer. The quadrivalent HPVvaccination has entered into the routine vaccination schedule in many European countries for use in children andadolescents between 9-15 years of age and for women between 16-26 years of age, whereas it has been proposedthat the bivalent vaccination should be given to girls between 9-18 years of age. While cervical cancer is amongthe cancers that can be prevented, it is essential to continue screening tests while introducing vaccination in asystematic manner for protection. On this subject, among the most important roles of nurses is to implementthe screening programs by fulfilling the caregiving, training and consultancy roles for the society and especially,for high risk groups and to increase the awareness of the people.     

Role of the HPV DNA Test in Follow-up of Treated Cervical Intraepithelial Neoplasia in Bangladesh

Background: Cervical cancer is a major public health problem in Bangladesh. Persistence of high riskhuman papillomavirus (HRHPV) influences the progression of the disease, with an important role in followupfor cervical intraepithelial neoplasia (CIN). Objective: To establish application of high risk HPV DNA testin the follow-up of women after treatment of CIN. Materials and Methods: This cross-sectional and hospitalbased study was carried out among 145 CIN treated women during the previous six months to three years at thecolposcopy clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka, between January 2011 and June2012. Pap smear and HPV samples were collected and colposcopy was performed to find out the persistence ofthe disease. Cervical samples obtained were tested for HPV DNA using the Hybrid Capture II (HC-II) test. Acervical biopsy was collected whenever necessary. The results were compared to assess the efficacy of differentmethods during follow up such as Pap smear, HPV test and colposcopy. Results: Mean age of the recruitedwomen (n=145) was 33.6 (± 7.6), mean age of marriage was 16.8 (±2.9) and mean age of 1st delivery was 18.8(±3.5) years. More than half had high grade CIN before treatment and 115 (79.3%) women were managed byLEEP and 20.7% were managed by cold coagulation. Among the 145 treated women, 139 were negative forHPV DNA and six of them (4.1%) were HPV positive. Sensitivity of Pap smear (40.0) and HPV DNA test (40.0)was poor, but specificity was quite satisfactory (>93.0) for all the tests. Conclusions: The high risk HPV DNAtest can be an effective method of identifying residual disease. It can be added to colposcopy and this should beapplied to all treated women attending for their first or second post-treatment follow-up visit at 6 months to oneyear, irrespective of the grade of treated CIN.     

Cost-Effectiveness of HPV Vaccination in the Prevention of Cervical Cancer in Malaysia

Introduction: Cervical cancers (CC) demonstrate the second highest incidence of female cancers in Malaysia.The costs of chronic management have a high impact on nation’s health cost and patient’s quality of life that canbe avoided by better screening and HPV vaccination. Methodology: Respondents were interviewed from sixpublic Gynecology-Oncology hospitals. Methods include experts’ panel discussions to estimate treatment costsby severity and direct interviews with respondents using costing and SF-36 quality of life (QOL) questionnaires.Three options were compared i.e. screening via Pap smear; quadrivalent HPV Vaccination and combined strategy(screening plus vaccination). Scenario based sensitivity analysis using screening population coverage (40-80%)and costs of vaccine (RM 300-400/dose) were calculated. Results: 502 cervical pre invasive and invasive cervicalcancer (ICC) patients participated in the study. Mean age was 53.3 ± 11.21 years, educated till secondary level(39.39%), Malays (44.19%) and married for 27.73 ± 12.12 years. Life expectancy gained from vaccination is13.04 years and average Quality Adjusted Life Years saved (QALYs) is 24.4 in vaccinated vs 6.29 in unvaccinated.Cost/QALYs for Pap smear at base case is RM 1,214.96/QALYs and RM 1,100.01 at increased screening coverage;for HPV Vaccination base case is at RM 35,346.79 and RM 46,530.08 when vaccination price is higher. Incombined strategy, base case is RM 11,289.58; RM 7,712.74 at best case and RM 14,590.37 at worst case scenario.Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher is highly costeffective at RM 946.74 per QALYs saved and this is followed by combined strategy at RM 35,346.67 per QALYssaved. Conclusion: Vaccination increase life expectancy with better QOL of women when cancer can be avoided.Cost effective strategies will include increasing the Pap smear coverage to 70% or higher. Since feasibility andlong term screening adherence is doubtful among Malaysian women, vaccination of young women is a more costeffective strategy against cervical cancers.     

Knowledge,Attitude and Practice of Commercial Sex Workers Regarding Cervical Cancer and Its Screening,Daulatdia Brothel,Rajbari District,Bangladesh, 2020-2021

Background: Cervical cancer is the second most common cancer in females in Bangladesh. This is caused by Human Papilloma Virus (HPV). Multiple sex partners, HIV infection, smoking, using birth control pills, and having more than three children are risk factors of cervical cancer. Hence, female sex workers have a high prevalence of infection with high risk HPV genotypes which eventually may causes cervical cancer. Unfortunately, the status of knowledge, attitude and practice among female sex workers regarding cervical cancer is mostly unknown. The aim of the study was to assess the knowledge, attitude and practice of women living in Daulatdia brothel regarding cervical cancer and its screening.  Methods: A cross-sectional knowledge-practice survey was conducted among 400 female sex workers in Daulatdia Brothel, Rajbari District, Bangladesh. The women’s total score on knowledge, and practice were categorized as sufficient or insufficient. We calculated frequencies and used binary logistic regression to describe and assess the association between scores and socio-demographic characteristics of respondents. Results: Most sex workers (61%) were between 29 to 35 years, married at 13 to 15 years of age, and divorced (91%). Middle aged sex workers were more likely have a VIA test  than women in the 29 to 35 years group (18%, OR:5.2; CI: 2.0, 13.5). Less than half of the studied women (40%) had sufficient knowledge regarding cervical cancer and 12% knew that infection by HPV is a risk factor. Respondents with primary and secondary education were more likely to have sufficient knowledge than the illiterate (42%, OR: 1.32; CI: 0.82, 2.12). Practices to prevent cervical cancer were very poor. Nearly all women (99%) would recommend other women to have a VIA test. There were only 7% who had a VIA test and 2% were vaccinated against HPV. Unmarried sex workers were more likely to take action to prevent cervical cancer. Sex workers educated up to the primary level were more likely to have a VIA or other tests than the illiterate sex workers (10%, OR: 1.3; CI: 0.6, 3.2). Conclusion: Sex workers in Daulatdia brothel were less knowledgeable about cervical cancer and less likely to have a VIA test and poor practices towards preventing cervical cancer. The sex workers underutilized the VIA test and HPV vaccine.     

VIA-VILI结合电子阴道镜检随访筛查早期发现宫颈病变

目的 在宫颈癌高发区通过对高危人群实施跟踪随访筛查以达到宫颈癌早期诊断和早期治疗。方法 对目标人群的30~59岁适龄妇女应用醋染（VIA）和碘染（VILI）进行初筛,结合子阴道镜检和病理检查进而明确诊断。结果 2006~2007年共筛查5595人,随访检查3676人,最终病理诊断结果证实CIN Ⅰ189例,CIN Ⅱ25例,CIN Ⅲ/原位癌19例,宫颈浸润癌8例。结论 碘染、醋染作为宫颈癌的初筛方法其符合率分别为41.6%和64%,但结合阴道镜及镜下定位活检病理检查可大大提高宫颈癌癌前病变及早期宫颈癌的诊断率。     

Detection of High-Risk Human Papillomaviruses in the Prevention of Cervical Cancer in India

Human papillomaviruses (HPVs) are small, non-enveloped, double-stranded DNA viruses that infect epithelial tissues. Specific genotypes of human papillomavirus are the single most common etiological agents of cervical intraepithelial lesions and cervical cancer. Cervical cancer usually arises at squamous metaplastic epithelium of transformation zone (TZ) of the cervix featuring infection with one or more oncogenic or high-risk HPV (HRHPV) types. A hospital- based study in a rural set up was carried out to understand the association of HR-HPV with squamous intraepithelial lesions (SILs) and cervical cancer. In the present study, HR-HPV was detected in 65.7% of low-grade squamous intraepithelial lesions (LSILs), 84.6% of high grade squamous intraepithelial lesions (HSILs) and 94% of cervical cancer as compared to 10.7% of controls. The association of HPV infection with SIL and cervical cancer was analyzed with Chi square test (p<0.001). The significant association found confirmed that detection of HR-HPV is a suitable candidate for early identification of cervical precancerous lesions and in the prevention of cervical cancer in India.     

Accuracy of Combined Visual Inspection with Acetic Acid and Cervical Cytology Testing as a Primary Screening Tool for Cervical Cancer: a Systematic Review and Meta-Analysis

Background: The performance of combined testing visual inspection with acetic acid (VIA) and cervicalcytology tests might differ from one setting to another. The average estimate of the testing accuracy across studiesis informative, but no meta-analysis has been carried out to assess this combined method. Objective: The objectiveof this study was to estimate the average sensitivity and specificity of the combined VIA and cervical cytologytests for the detection of cervical precancerous lesions. Materials and Methods: We conducted a systematic reviewand a meta-analysis, according to the Cochrane Handbook for Systematic Review of Diagnostic Test Accuracy.We considered two cases. In the either-positive result case, a positive result implies positivity in at least one ofthe tests. A negative result implies negativity in both tests. In the both-positive case, a positive result implieshaving both tests positive. Eligible studies were identified using Pubmed, Embase, Website of Science, CINHALand COCRANE databases. True positive, false positive, false negative and true negative values were extracted.Estimates of sensitivity and specificity, positive and negative likelihood (LR) and diagnostic odds ratios (DOR)were pooled using a hierarchical random effect model. Hierarchical summary receiver operating characteristics(HSROC) were generated and heterogeneity was verified through covariates potentially influencing the diagnosticodds ratio. Findings: Nine studies fulfilled inclusion criteria and were included in the analysis. Pooled estimatesof the sensitivities of the combined tests in either-positive and both-positive cases were 0.87 (95% CI: 0.83-0.90)and 0.38 (95% CI: 0.29-0.48), respectively. Corresponding specificities were 0.79 (95% CI: 0.63-0.89) and 0.98(95% CI: 0.96-0.99) respectively. The DORs of the combined tests in either-positive or both-positive result caseswere 27.7 (95% CI: 12.5-61.5) and 52 (95% CI: 22.1-122.2), respectively. When including only articles withoutpartial verification bias and also a high-grade cervical intraepithelial neoplasia as a threshold of the disease,DOR of combined test in both-positive result cases remained the highest. However, DORs decreased to 12.1 (95%CI: 6.05-24.1) and 13.8 (95% CI: 7.92-23.9) in studies without partial verification bias for the combined tests inthe either-positive and both-positive result cases, respectively. The screener, the place of study and the size ofthe population significantly influenced the DOR of combined tests in the both-positive result case in restrictionanalyses that considered only articles with CIN2+ as disease threshold. Conclusions: The combined test in theeither-positive result case has a high sensitivity, but a low specificity. These results suggest that the combined testshould be considered in developing countries as a primary screening test if facilities exist to confirm, throughcolposcopy and biopsy, a positive result.