Diagnostic Accuracy of the Rapid Human Papillomavirus Oncoprotein E6/E7 Antigen Test for Cervical Cancer Screening in a Low-Resource Setting: A Cross-Sectional Study

Diagnostic Accuracy of the Rapid Human Papillomavirus Oncoprotein E6/E7 Antigen Test for Cervical Cancer Screening in a Low-Resource Setting: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Diagnostic Accuracy of the Rapid Human Papillomavirus Oncoprotein E6/E7 Antigen Test for Cervical Cancer Screening in a Low-Resource Setting: A Cross-Sectional Study Talai KC¹, Philippe Poli A, Itsura PM, Banchir RM, Kapten M, Cheruyiot EK, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6852002/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background : Persistent high-risk human papillomavirus is responsible for 95% of all cases of cervical cancer worldwide. Screening for high-risk genotypes has been acknowledged as the gold standard for the elimination of cervical cancer. However, most low- and middle-income countries have limited access to this screening method because ofa lack of adequate sustainable resources. Objective : This study aimed to compare the diagnostic accuracy of the rapid high-risk human papillomavirus 16/18 oncoprotein E6/E7 antigen test to that of the polymerase chain reaction (PCR) deoxyribonucleic acid test among women who presented to family planning and dysplasia clinics at Moi Teaching and Referral Hospital. Methods : This was a cross-sectional study performed between February and July 2024 to compare the diagnostic accuracy of the rapid high-risk human papillomavirus 16/18 oncoprotein E6/E7 antigen test to that of the polymerase chain reaction deoxyribonucleic acid test among women who underwent cervical cancer screening at Moi Teaching and Referral Hospital. Two hundred and fifty-seven (257) women aged 30 years and older were randomly selected for this study. A cervical swab was obtained from all participants for human papillomavirus polymerase chain reaction deoxyribonucleic acid testing, followed by cervical sample collection using the Delphi vaginal self-sampler for the rapid human papillomavirus oncoprotein E6/E7 antigen test. To achieve the objective of the study, sensitivity, specificity, positive predictive value, and negative predictive value were measured. Data on sociodemographicand clinical characteristics were collected and analysed. The significance of the data was set at a two-tailed p<0.05. The chi-squaretest was used to compare categorical variables. Fisher’s exact test or the Monte Carlo correction was used for the chi-square analysis when more than 20% of the cells had an expected count <5. Results : The sensitivity of the rapid oncoprotein E6 and E7 test was 99.33%, and the specificity was 99.07%. In addition, the positive predictive value and negative predictive value were 99.33% and 99.07%, respectively. Furthermore, the accuracy of the rapid oncoprotein E6/E7 test was 99.22%. These findings were statistically significant (p <0.001, 95% CI=0.98–1.00), and the AUC for the rapid oncoprotein E6/E7 test was 0.992. Conclusion : The accuracy of the rapid high-risk human papillomavirus mRNA oncoprotein E6/E7 antigen test is as good as that of the polymerase chain reaction deoxyribonucleic acid test for cervical cancer screening in low-resource settings. Oncoproteins E6 and E7 diagnostic accuracy mRNA sensitivity and specificity positive predictive value negative predictive value Figures Figure 1 Figure 2 Introduction Persistent high-risk human papillomavirus (HR-HPV) is responsible for 95% of all cases of cervical cancer worldwide [ 1 ]. In low- and middle-income countries, the prevalence of HR-HPV and the incidence of cervical cancer remain high due to limited access to preventive measures and treatment [ 2 ]. Most of these countries lack acceptance of primary prevention measures and lack access to accurate and cost-effective screening methods [ 3 ]. The cervical HPV test, especially the polymerase chain reaction deoxyribonucleic acid (PCR DNA) test, has been acknowledged as the standard cervical cancer screening modality because of its high sensitivity and specificity. This test has offered a great opportunity to improve the effectiveness of cervical cancer screening [ 3 , 4 , 7 , 6 ]. The WHO global strategy has established three targets to be achieved by the year 2030 to position all countries on the pathway to eliminate this deadly and preventable disease [ 1 ]. However, sub-Saharan Africa (SSA), the cradle of HR-HPV and cervical cancer, has been struggling to achieve the World Health Organization’s goal to eliminate cervical cancer through the prevention, screening, and treatment of premalignant cervical cancer lesions and early cervical cancer [1˗3]. To date, studies have shown that laboratory tests for the detection of high-risk HR-HPV are more sensitive and reliable than conventional cytology and visual inspection using acetic acid and/or Lugol iodine [ 5 , 8 , 9 , 10 , 11 ]. The currently available evidence has shown that both the sensitivity and specificity of the high-risk HPV DNA screening test are less for adenocarcinoma [ 12 ], but very good for squamous cell carcinoma, except [ 13 ]. Despite its acknowledgement as the gold standard screening method, its high cost, sophisticated equipment that requires additional training, the need for electricity, the need for regular maintenance of the equipment, expensive reagents, and long turnaround time of up to 2 weeks limit HPV DNA testing in low- and middle-income countries (LMICs) [ 13 ]. Economic assessments are relevant to support the decision to incorporate more cost-effective strategies for the screening and treatment of cervical cancer at LMICs [ 14 ]. The challenges in LMICs are numerous, and the lower socioeconomic status (SES) of most women in those countries unfortunately affects their health care-seeking behaviour, as poor health care literacy compromises their compliance with medical advice and their understanding of the diagnosis of their health problems. For example, a positive HR-HPV test may increase anxiety among women, although HPV infections are transient in most women. The current WHO guidelines for the screening of cervical cancer in LMICs are challenged by limited resources, and thus follow-up after positive results are obtained at first screening can be difficult [ 14 ]. According to the WHO, several HPV tests are available: some HPV tests detect DNA, while other HPV tests detect the oncoprotein E6/E7 mRNA [ 15 ]. Tests that are currently commercially available and that are being used in some countries for cervical cancer screening include the Hybrid Capture 2 (Qiagen), CareHPV (Qiagen), Cobas HPV Test (Roche), Cervista (Hologic), Aptima HPV Assay (Hologic), BD HPV Assay (BD) and Xpert HPV (Cepheid) [ 15 , 16 ]. In selecting which HPV test will be used in a given screening program, consideration should be given to the results of clinical trials, clinical validation of the test, and other operational and logistical aspects of the test and its requirements [ 16 ]. The carcinogenesis of the cervix is mediated by the HPV-E6 and E7 oncoproteins, which are biomarkers that are useful for managing women with positive screening results. To date, evidence has established that these 2 oncoproteins play a major role in promoting and maintaining cervical carcinogenesis, as they are overexpressed during cervical transformation [ 14 , 17 ]. The oncoprotein E6 plays a major role in cell immortalization, as it binds to the tumour suppressor protein p53, which is usually activated in normal cells in response to DNA damage. This binding degrades p53 and prevents the cell from undergoing apoptosis [ 17 ]. When the oncoprotein E7 interacts with host proteins, it binds to the cellular tumour suppressor pRb, which leads to its degradation, preventing it from inactivating transcription factors and promoting cell proliferation [ 18 ]. In addition, the overexpression of E6 and E7 leads to the accumulation of genetic errors in cells over time, which when combined with viral gene deregulation, drives invasive cancer [ 19 , 20 ]. Thus, oncoproteins E6 and E7 are interesting markers of persistent HR-HPV infection and associated precancerous lesions. Readers may ask what the difference is between the test for the E6 and E7 oncoproteins and the HPV DNA genotype test in cervical cancer screening. The oncoproteins E6 and E7 differ according to HPV genotype. Thus, tests must target oncoproteins from diverse oncogenic types to ensure high sensitivity and specificity [ 21 ]. The clinical accuracy of E6 or E7 DNA and RNA assays has been demonstrated in several studies [ 14 , 16 , 21 ]. However, few studies in sub-Saharan Africa have been conducted to determine the accuracy of rapid HR-HPV mRNA oncoprotein E6/E7 detection. To fill this gap, this study aimed to determine the diagnostic accuracy of the HR-HPV mRNA oncoprotein E6/E7 test in a low-resource setting as a cost-effective cervical cancer screening modality. Materials and methods Study design, setting, and population This was a cross-sectional study performed at Moi Teaching and Referral Hospital, the second-largest national hospital in Kenya. This multispecialty hospital, which serves a population of over 25 million people in Kenya, parts of Eastern Uganda, South Sudan, Northern Tanzania, and the Democratic Republic of the Congo, is known for its high-quality health care. In partnership with the Academic Model Providing Access to Health care (AMPATH), the hospital offers screening, prevention, and treatment for gynaecological cancers. Since screening for the cervical program started in 2009, hospitals and their satellites have essentially used visual inspection with acetic acid, and occasionally, Pap cytology and HPV PCR DNA testing. The government of Kenya approved and adopted the HPV PCR DNA test as the gold standard screening method for cervical cancer in 2018; however, the high cost of the test and other constraints previously mentioned have limited its implementation in rural areas. In November 2023, a feasibility study was conducted using rapid testing of HPV oncoproteins E6 and E7, Pap cytology, and PCR. This feasibility study enrolled 185 participants. Both samples collected by the patients and those collected by clinicians were used for rapid testing of HPV oncoproteins E6 and E7. For the current study, 257 participants were included. All women aged between 30 and 65 years who attended the family planning and dysplasia clinics at Moi Teaching and Referral Hospital within the study period and who provided informed consent to participate in this study were included. Considering the short period of data collection, pregnant women, women aged less than 30 years, and women with confirmed diagnoses of cervical cancer were excluded. Those who were menstruating were temporarily excluded until bleeding ceased. All eligible women were approached and given information about cervical cancer screening and the study, methods of sample collection, the two HR‒HPV tests, and the meaning of the results (negative and positive) before providing informed consent. Figure 1 illustrates the recruitment process for the participants. The data collection was conducted by experienced and trained research assistants, including 2 registered nurses (RNs), 3 medical doctors, and 1 social worker. Written informed consent was obtained from each participant. Women who could not read or write were assisted by a social worker in the presence of either a relative or a social worker. Questionnaire survey The research assistants (nurses and doctors) administered a questionnaire that was developed in English and translated into Kiswahili. The data included sociodemographic and clinical characteristics. The research assistants provided counselling to each study participant and explained the implications of an HR-HPV-positive result. Three to four weeks after the HPV sampling, the participants received results either through a message (those with negative results) or in person (those with positive results). Sample collection for detection of the HPV oncoproteins E6 and E7 The eligible women were assisted by either the RN or the medical doctor during sample collection using the Delphi vaginal self-sampler (DVSS). All research assistants were trained for 3 months before the start of the study, and then, refresher training was performed 3 days before the enrolment of participants. The kits did not contain expired materials, and precautions were taken to avoid cross-contamination of the samples; a new specimen collection container was used for each sample. After the patient was placed on the gynaecological examination table and the speculum was inserted, the excess mucus discharge was removed from the cervix with a cotton ball and discarded. The DVSS was inserted, and the sample was collected according to the manufacturer’s instructions. This process was performed for each participant. The collected sample was immediately prepared for testing as described below. HPV DNA PCR sample collection The eligible women were assisted by either the RN or the medical doctor when HPV DNA was collected using an Evalyn Brush ® (Evalyn Rovers Medical Devices BV, the Netherlands) for HR‒HPV DNA tests. The Evalyn ® Brush is validated for use in PCR-based assays, which ensures the highest number of valid samples across all age groups. In addition, the use of a dry sample (with no liquid in the mail) makes it compatible with the Cobas ® 6800 or 4800 system for polymerase chain reaction (PCR). The collected HR-HPV DNA samples were transported daily to the Lancet-Kenya laboratory, Eldoret branch, and were stored in the Department of Pathology at room temperature (approximately 19–24 °C) for a maximum of 2 weeks. HPV oncoprotein E6 and E7 specimen testing The collected sample was prepared using a pipette (dropper). Eight (8) drops were extracted from the tube for each sample. Eight (8) drops of extraction buffer A were added to the extracted sample, and the mixture was shaken well. After 2 minutes, 8 drops of extraction buffer B were added to the sample, which was incubated with the buffer for 1 minute. Three drops (approximately 100 μl) were extracted from the tube to the sample well onto the cassette. For each prepared sample, the result was read within 15 minutes following extraction from the tube to the sample well onto the cassette. The result was positive when 2 coloured (red-like) bands appeared on the membrane (cassette): one band appeared in the control region (C), and another band appeared in the test region (T). In contrast, the result was negative when only one coloured band appeared in the control region, while the band in the test region (T) was not coloured. The appearance of a faint coloured band in the control region was reported as positive. The rapid test for HPV oncoproteins E6 and E7 is manufactured for the qualitative detection of the HR-HPV 16/18/13/45/52/58 E6 and E7 oncoproteins only, but without segregation, as in the HPV DNA PCR test. HPV DNA specimen testing The samples collected were also transferred daily to Lancet Kenya, Eldoret branch, for testing. The samples were processed biweekly using the Cobas ® 6800 system for HPV DNA polymerase chain reaction (PCR). This system detects the presence of 14 HR-HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The results are automatically interpreted by the HPV DNA PCR test system and are displayed graphically on a controller monitor screen as either ‘positive’ or ‘negative for a specific HR-HPV type [22, 23, 24, 25]. The samples were analysed by trained laboratory technicians from a certified laboratory, Cerba Lancet Kenya. This study did not receive ethics committee approval for a Pap test, which could have been impactful and useful. Clinical relevance of this study This study helps determine the clinical impact of using the rapid HR-HPV oncoprotein E6/E7 test, which is an affordable and accessible cervical cancer screening modality, and helps guide decision-making about whether to incorporate this test into routine practice in low-resource settings. Management of the results and future plans for participants The precaution of releasing positive results in a doctor’s office was adopted to reduce anxiety associated with such results. Appropriate counselling was provided to emphasize that HPV-positive results from the rapid HPV oncoprotein E6 and E7 test require confirmatory tests with HR-HPV PCR DNA. In addition, HR-HPV DNA PCR-positive results need to be paired with the results of another test—cytology or with—and patients should be referred for colposcopy and follow-up care [26, 27]. Statistical analyses The statistical analyses were conducted using the statistical software package SPSS V.20.0 (Armonk, NY: IBM Corp.). Qualitative data are presented as numbers and percentages. The Kolmogorov‒Smirnov test was used to verify the normality of the distribution. The quantitative data are presented as ranges (minimums and maximums), means, standard deviations, medians, and interquartile ranges (IQRs). Statistical analysis of the accuracy of the rapid HPV oncoprotein E6/E7 test quantified how well the test correctly identified individuals with or without a disease according to measures such as sensitivity, specificity, and predictive values. The rapid test reported the results as either positive or negative, whereas the HPV PCR DNA test quantitatively separated the results into 3 groups: HR-HPV 16, HR-HPV 18, and HR-HPV non-16/18. On the basis of the interpretation of the PCR DNA results, these results were reported as either positive or negative for the specific genotype mentioned above. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of HR-HPV in each test were calculated. A positive result was defined when both tests were positive or when either test was negative. The sensitivity of the tests refers to the proportion of individuals with human papillomavirus infection who were correctly identified by the test (true positives), whereas the specificity of the tests refers to the proportion of individuals without the disease who were correctly identified by the test (true negatives) [28]. The results of the two diagnostic tests were interpreted to determine whether the participants had or did not have high-risk human papillomavirus infection according to the predictive values (positive or negative). The probability that participants with positive test results were actually infected with HR-HPV was referred to as the positive predictive value, whereas the probability that those with negative results were actually negative was referred to as a negative predictive value [29]. Furthermore, the overall diagnostic ability of the test to provide an accurate diagnosis was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) [30, 31]. The ROC curve results graphically displayed the effective sensitivity for each specificity for high-risk human papillomavirus infection. The significance of the results was judged at the 5% level. Results Sociodemographic characteristics The mean age of the participants was 40.8 ± 9.1 years, as described in Table 1. Women aged between 40 and 50 years accounted for 38.1% of all patients, while those aged between 30 and < 40 years accounted for 45.5%. With respect to the marital status of the participants, most were married women and widows and represented 58.4% and 17.9% of all patients, respectively. Participants with primary and secondary education levels were almost equally represented. More than half of the participants were unemployed (see Table 1). HPV status of the participants With respect to the HPV status of the participants, 58.0% reported positive results for rapid tests that used mRNA, whereas 42% of the participants tested negative. For the PCR test, 7.4% of the participants tested positive for high-risk HPV 16, whereas 3.1% tested positive for high-risk HPV 18. In addition, 33.5% of the participants tested positive for non-high-risk HPV 16/18 (see Table 2). Table 3 shows the concordance between the rapid oncoprotein E6/E7 and PCR DNA tests in 77% of the cases. Accuracy of rapid HR-HPV oncoprotein detection Table 4 shows that the sensitivity of the rapid oncoprotein E6 and E7 test was 99.33% and that the specificity was 99.07%. In addition, the positive and negative predictive values were 99.33% and 99.07%, respectively. The accuracy of the rapid oncoprotein E6 and E7 test was 99.22%. These findings were statistically significant (p <0.001, 95% CI=0.98–1.00), and the AUC for the rapid oncoprotein E6 and E7 test was 0.992. The accuracy of the HR‒HPV PCR DNA test was individually assessed according to the human papillomavirus genotypes, as summarized in Table 4 and graphically demonstrated in Figure 2. The sensitivity and specificity for HR-HPV 16 were 89.26% and 100.0%, respectively. In addition, the positive and negative predictive values for the HR-HPV 16 PCR DNA test were 100.0% and 87.10%, respectively. The accuracy of the HR-HPV 16 PCR DNA test was 93.77%, with an AUC of 0.946. This difference was statistically significant (p <0.001, 95% CI=0.92–0.98). For HR-HPV 18, the sensitivity and specificity were 95.30% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 93.91%, respectively, with an estimated diagnostic accuracy of 97.28% and an AUC of 0.977. This difference was statistically significant (p<0.001, 95% CI=0.96–0.99). With respect to the PCR DNA test for HR-HPV non-16/18, the sensitivity and specificity of the test were 39.60% and 100.0%, respectively, whereas the positive and negative predictive values were 100.0% and 54.55%, respectively. The accuracy of the PCR DNA test for HR-HPV non-16/18 was 64.98%, with an AUC of 0.698. This difference was statistically significant (p<0.001, 95% CI=0.64–0.76). Discussion The overall positive rate of the HR-HPV oncoproteins E6/E7 observed in the present study was lower (58.0% vs. 70%) than that reported in Brazil by Valença, J. E. C et al. (2016) [ 32 ] and the 100% positive rate reported in a Korean study [ 33 ]. In contrast with the current study, both the Brazilian and Korean studies were conducted on patients who were diagnosed with low-grade and high-grade squamous intraepithelial lesions. The three studies used HR-HPV tests targeting the E6 and E7 mRNAs using different kits with novel technologies. The current study used qualitative E6 and E7 tests, whereas the 2 previous studies used quantitative E6 and E7 mRNA tests [ 32 , 33 ] to identify the specific HR-HPV genotype. Although the qualitative E6 and E7 mRNA tests used could not specify the HR-HPV genotype, the tests were able to report positivity for the E6/E7 oncoproteins, while the PCR DNA test separated the results into the HPV 16, HPV 18, or non-HPV 16/18 groups. The low positivity rates reported in this study may be related to the grade of the cervical lesions (low grade), which is currently difficult to determine. Follow-up care with colposcopy or cytology and biopsy for those with positive test results is important. However, previous studies have shown that the mRNA positivity rate is increased in patients with more severe cervical intraepithelial lesions [ 34 , 35 ]. The sensitivity of the oncoprotein E6/E7 mRNA reported in this study was greater than that reported by Benevolo, M., and colleagues (2011) [ 34 ], and recently, that by Downham, L., et al. (2024) [ 36 ]. In contrast to the current study findings, the other 2 studies were conducted under similar circumstances in patients who were diagnosed with cervical intraepithelial neoplasia (CIN) or abnormal cytology. In the first study, the sensitivity varied according to the severity of CIN. For example, Benevolo M. et al. reported an HPV mRNA sensitivity of 83% in atypical squamous cells of undetermined significance (ASCUS), 62% in low-grade squamous intraepithelial lesions (LSILs), and 67% in high-grade squamous intraepithelial lesions (HSILs) [ 34 ]. However, the corresponding sensitivities in the same study were 99%, 91%, and 96% for the HR-HPV DNA PCR test [ 34 ]. In one recent systematic review, the pooled sensitivity of an enzyme-linked immunosorbent assay (ELISA) (100% vs. 18%) was reported, whereas the pooled sensitivity of a multiplex HPV serology assay was reported to be 16% [ 37 ], which is lower than the sensitivity reported for the rapid detection of HPV mRNA. As in the APTIMA mRNA study, the higher sensitivity compared with that in previous studies may be because the samples were collected by clinicians versus the patients. In the present study, the sensitivity of the HR-HPV PCR DNA test was low for the detection of HR-HPV 16 and 18 and extremely low for HR-HPV non-16/18 compared with the sensitivity of the rapid oncoprotein E6/E7 test. This is difficult to explain because the sensitivity of the diagnostic test is not influenced by the prevalence of the disease [ 30 , 31 , 32 , 33 ]. In addition, PreTect HPV-Proofer was used to detect the mRNAs of the HPV oncoproteins E6 and E7, whereas the current study used the rapid HPV oncoprotein E6 and E7 mRNA test method. In the Aptima study [ 38 ], the sensitivity was 96.3%, which was similar to what was reported in the current study. These findings indicate that mRNA oncoprotein tests are good cervical cancer screening modalities, especially in low- and middle-income countries. In this study, the specificity of the current rapid E6/E7 oncoprotein test was greater than that reported by Benevolo M. et al. [ 34 ]. In the study by Benevolo and colleagues, low specificity was observed, especially for ASCUS and LSIL (63.2% vs. 82 and 76), while higher specificity was found for HSIL [ 34 ]. The Pap test was not approved by the ethics committee for the current study, and thus any data comparison is difficult. One systematic review revealed that HPV16 and HPV18 oncoprotein E6 and E7 antibodies have high specificity but low sensitivity for detecting cases of cervical cancer or CIN2/3 precancerous lesions [ 36 ]. In the Aptima study, the specificity of the LSIL was 43.2%, which was lower than the specificity reported in the current study. In contrast, the specificity of the HR-HPV DNA PCR test was optimally greater, which supports the superiority of tests excluding false positivity, whereas the Aptima study reported a specificity of 85%. Although the specificity of the HR-HPV DNA PCR test was 100% in the current study, several studies have reported low specificity of the HR-HPV DNA test and high specificity for HR-HPV mRNA tests (specificity as low as 29%, 13%, and 4% for ASCUS, LSIL, and HSIL, respectively) [ 2 , 3 , 39 ]. This is because high-risk HPV tests have low specificity in detecting high-grade cervical intraepithelial neoplasia (CIN2 or CIN3) [ 39 , 40 ]. The positive predictive value (PPV) in the current study was comparable to that reported in another HPV mRNA study (99% vs. 96%) [ 41 ] and higher than that reported in yet another study, (80%) [ 31 ]. However, the PPV reported in this previous study was exclusively for HSIL. The difference may be partially due to the different use purposes of HPV mRNA tests between the studies. The current study uses HPV mRNA tests as screening tests, whereas the other 2 studies used mRNA tests as triage tests to reduce the need for referrals for colposcopy. In the Ugandan study, the positive predictive value for the detection of any HR-HPV E6/E7 mRNA for the presence of CIN 2 + was 8.2% [ 42 ], which was lower than that reported with rapid HPV mRNA tests. In addition, the positive predictive value associated with the detection of HPV-16 mRNA was 15%, and that for the detection of HPV-18/45 mRNAs was 15% lower [ 43 ]. In contrast to the current hospital-based study, the Ugandan study was a community-based screening study. However, the positive predictive value of the HPV DNA PCR test was reported to be 100% for HR-HPV 16 and 18. This finding contrasts with what was observed by Aydogan Kirmizi, D. et al. (2021), who reported a PPV of 66.7% for LSIL and 70.0% for HSIL [ 41 ], which is similar to what was reported by Kaya Terzi, N. (2021) [ 44 ]. In this study, the negative predictive value was 100%, which is higher than the 91.9% recently reported by Kittisiam, T., et al. (2024) [ 45 ]. Few studies have been published on the negative predictive value of HPV DNA and mRNA. The findings from the present study revealed that the accuracy of the rapid HPV mRNA test was greater than that of the HPV DNA test (99.07% vs. 87.10% for HPV16, 93.03% for HPV18, and 54.55% for HR-HPV non-16/18). These results are similar to observations made by the WHO through the generation data group (GDG) regarding the accuracy of HPV mRNA tests vs. HPV DNA tests [ 46 , 47 , 48 ]. In a recent systematic review conducted by Arbyn M. and colleagues [ 22 ], HPV mRNA tests, especially the APTIMA HPV assay, which targets the E6/E7 mRNA of HR-HPV, showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies [ 22 ]. In contrast to APTIMA, the rapid HPV assay targeting E6/E7 of HR-HPV16/18 showed high sensitivity and specificity as a promising primary screening test. The differences between the APTIMA and the rapid HR-HPV screening tests include the following: APTIMA is a quantitative test with a turnaround of 3–4 hours, which is similar to the GeneXpert HPV DNA tests, whereas the rapid HR-HPV 16/18 test is a qualitative test with a turnaround of 15 minutes. The performance of the rapid oncoprotein E6/E7 test as a screening modality is similar to that of the PCR DNA test. Figure 2 shows this result better, as the AUC values of the tests were interpreted and compared with those of the HR-HPV genotypes. The ROC curve shows that the rapid oncoprotein E6/E7 test is highly accurate. Mander and colleagues reported that a diagnostic test is useful when its sensitivity and specificity are greater than 50% [ 30 ]. Therefore, the integration of rapid oncoprotein E6/E7 tests as a cervical cancer screening modality in LMICs will positively impact the strategy of eliminating cervical cancer. Conclusions The high sensitivity and relative specificity of the rapid HR-HPV E6 and E7 mRNA test support its use for primary cervical cancer screening. However, women with positive HR-HPV results should be referred for colposcopy and further follow-up care. Large-scale and longitudinal studies are needed to validate the rapid detection of E6/E7 oncoproteins as a primary cervical cancer screening method at the community level. Strengths and limitations This study demonstrated that the rapid HPV oncoprotein test is as accurate as the PCR DNA test for cervical cancer screening. The negative predictive value observed is comparable to that of the PCR DNA test. The inclusion of faint results increases the number of false-positive results. Women with positive rapid HPV oncoprotein results should be referred for colposcopy. This study did not receive ethics committee approval for the Pap test to be performed on the study participants. Abbreviations ASCUS : Atypical squamous cells of undetermined significance AUC : Area under the curve CIN : Cervical intraepithelial neoplasia DNA : Deoxyribonucleic acid HPV : Human papillomavirus HR : high-risk HSIL : high-grade squamous intraepithelial lesions LSIL : low-grade intraepithelial lesions mRNA : messenger RNA NPV : negative predictive value PCR : Ribonucleic acid PPV : positive predictive value RNA : Ribonucleic acid ROC : Receiver operating characteristic Declarations Human Ethics approval and consent to participate : This study received approval from the MTRH/MU-Institutional Research and Ethics Committee (IREC) under the approval number FAN: 0004670 and the National research permit number NACOSTI/P/24/33601. Clinical Trial : Not applicable Consent for publication : Consent was obtained during enrolment in the study. Availability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. Competing interests : None to declare Funding : No other funds were received. Authors' contribution contributors : All the authors reviewed the manuscript. Conceptualization, investigation, and methodology were performed by the TKC, PPA, and MEW. Project administration and resources were performed by (KM, CEK, MK, BRM, OBE, NJN, MB, KK, KWK, MRM, AWK). Supervision, data curation, and formal analysis were performed by PPA, IPM, TPK, and MEW. Validation, visualization, and rewriting of the manuscript were performed by all the authors (TKC, PPA, MEW, KM, CEK, MK, BRM, OBE, NJN, MB, KK, KWK, MRM, AWK, IPM, and TPK). Acknowledgements : We acknowledge the management of Moi Teaching and Referral Hospital for supporting the initiative of conducting this research. References GÜLTEKİN, M., Ramirez, P., Broutet, N., & Hutubessy, R. 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A., Ferenczy, A., et al (2017). Introduction of molecular HPV testing as the primary technology in cervical cancer screening: Acting on evidence to change the current paradigm. Preventive Medicine, 98, 5-14. Segura, M. E. D. A. (2019). Comments on: limitations of HPV DNA testing in screening of cervical adenocarcinomas. Revista Brasileira de Ginecologia e Obstetrícia, 41(02), 133-134. Harty, E., Carr, S., Doyle, Z., & Hespe, C. (2023). Cervical screening using HPV-DNA cytology in a low-income setting: an audit within a socio-economically deprived rural community in the Philippines. Journal of Global Health Reports, 7, e2023047. Casas, C. P. R., Albuquerque, R. D. C. R. D., Loureiro, R. B., Gollner, A. M., Freitas, M. G. D., Duque, G. P. D. N., et al (2022). Cervical cancer screening in low-and middle-income countries: A systematic review of economic evaluation studies. Clinics, 77, 100080. World Health Organization. (2021). WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention: use of mRNA tests for human papillomavirus (HPV). World Health Organization. World Health Organization. (2020). WHO technical guidance and specifications of medical devices for screening and treatment of precancerous lesions in the prevention of cervical cancer. World Health Organization. Malla, R., & Kamal, M. A. (2021). E6 and E7 oncoproteins: Potential targets of cervical cancer. Current Medicinal Chemistry, 28(39), 8163-8181. Araldi, R. P., Sant’Ana, T. A., Módolo, D. G., de Melo, T. C., Spadacci-Morena, D. D., de Cassia Stocco, R., et al (2018). The human papillomavirus (HPV)-related cancer biology: An overview. Biomedicine & pharmacotherapy, 106, 1537-1556. Boccardo, E., Manzini Baldi, C. V., Carvalho, A. F., Rabachini, T., Torres, C., Barreta, L. A., et al (2010). Expression of human papillomavirus type 16 E7 oncoprotein alters keratinocytes expression profile in response to tumor necrosis factor-α. Carcinogenesis, 31(3), 521-531. Yeo-Teh, N. S., Ito, Y., & Jha, S. (2018). High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. International journal of molecular sciences, 19(6), 1706. McBride, A. A., & Warburton, A. (2017). The role of integration in oncogenic progression of HPV-associated cancers. PLoS pathogens, 13(4), e1006211. Arbyn, M., Simon, M., Peeters, E., Xu, L., Meijer, C. J., Berkhof, J., et al (2021). 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clinical Microbiology and Infection, 27(8), 1083-1095. Saville, M., Sultana, F., Malloy, M. J., Velentzis, L. S., Caruana, M., Ip, E. L., et al (2019). Clinical Validation of the cobas HPV Test on the cobas 6800 System for the Purpose of Cervical Screening. Journal of Clinical Microbiology, 57(2), 10-1128. Sundström, K., Lamin, H., & Dillner, J. (2021). Validation of the cobas 6800 human papillomavirus test in primary cervical screening. PLoS One, 16(2), e0247291. Frayle, H., Gori, S., Rizzi, M., Graziani, B. N., Vian, E., Giorgi Rossi, P., et al (2019). HPV testing for cervical cancer screening: technical improvement of laboratory logistics and good clinical performance of the cobas 6800 in comparison to the 4800 system. BMC Women's Health, 19, 1-7. Mutombo, A. B., Benoy, I., Tozin, R., Bogers, J., Van Geertruyden, J. P., & Jacquemyn, Y. (2019). Prevalence and distribution of human papillomavirus genotypes among women in Kinshasa, the Democratic Republic of the Congo. Journal of Global Oncology, 5, 1-9. Polman, N. J., Veldhuijzen, N. J., Heideman, D. A., Snijders, P. J., Meijer, C. J., Berkhof, J. (2019). Management of HPV‐positive women in cervical screening using results from two consecutive screening rounds. International journal of cancer, 144(9), 2339-2346. Shreffler, J., & Huecker, M. R. (2020). Diagnostic testing accuracy: Sensitivity, specificity, predictive values and likelihood ratios. Dhamnetiya, D., Jha, R. P., Shalini, S., & Bhattacharyya, K. (2022). How to analyze the diagnostic performance of a new test? Explained with illustrations. Journal of laboratory physicians, 14(01), 090-098. Hazra, A., & Gogtay, N. (2017). Biostatistics series module 7: the statistics of diagnostic tests. Indian journal of dermatology, 62(1), 18-24. Mander, G. T., & Munn, Z. (2021). Understanding diagnostic test accuracy studies and systematic reviews: A primer for medical radiation technologists. Journal of Medical Imaging and Radiation Sciences, 52(2), 286-294. Munkhdelger, J., Kim, G., Wang, H. Y., Lee, D., Kim, S., Choi, Y., et al (2014). Performance of HPV E6/E7 mRNA RT-qPCR for screening and diagnosis of cervical cancer with ThinPrep® Pap test samples. Experimental and Molecular Pathology, 97(2), 279-284. Benevolo, M., Vocaturo, A., Caraceni, D., French, D., Rosini, S., Zappacosta, R., et al (2011). Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test. Journal of clinical microbiology, 49(7), 2643-2650. Arbyn, M., Martin‐Hirsch, P., Buntinx, F., Van Ranst, M., Paraskevaidis, E., & Dillner, J. (2009). Triage of women with equivocal or low‐grade cervical cytology results: a meta‐analysis of the HPV test positivity rate. Journal of cellular and molecular medicine, 13(4), 648-659. Downham, L., Jaafar, I., Rol, M. L., Nyawira Nyaga, V., Valls, J., Baena, A., et al (2024). Accuracy of HPV E6/E7 oncoprotein tests to detect high-grade cervical lesions: a systematic literature review and meta-analysis. British Journal of Cancer, 130(4), 517-525. Singini, M. G., Singh, E., Bradshaw, D., Ramaliba, T., Chen, W. C., Motlhale, M., et al (2023). Usefulness of high‐risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta‐analysis. Journal of medical virology, 95(1), e27900. Ratnam, S., Coutlee, F., Fontaine, D., Bentley, J., Escott, N., Ghatage, P., et al (2011). Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer. Journal of Clinical Microbiology, 49(2), 557-564. Kim, M. A., Oh, J. K., Chay, D. B., Park, D. C., Kim, S. M., Kang, E. S., et al (2010). Prevalence and seroprevalence of high-risk human papillomavirus infection. Obstetrics & Gynecology, 116(4), 932-940. Valença, J. E. C., Gonçalves, A. K., Silva, I. D. C. G. D., Eleutério Junior, J., Silva, T. T. D., Bruneska, D., et al (2016). High risk HPV E6/E7 oncoprotein expression in women with high grade squamous intraepithelial lesion. Revista Brasileira de Ginecologia e Obstetrícia, 38, 154-159. Cuzick, J., Arbyn, M., Sankaranarayanan, R., Tsu, V., Ronco, G., Mayrand, M. H., et al (2008). Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine, 26, K29-K41. Cuzick, J., Clavel, C., Petry, K. U., Meijer, C. J., Hoyer, H., Ratnam, S., et al (2006). Overview of the European and North American studies on HPV testing in primary cervical cancer screening. International journal of cancer, 119(5), 1095-1101. Sørbye, S. W., Fismen, S., Gutteberg, T., & Mortensen, E. S. (2010). Triage of women with minor cervical lesions: data suggesting a “test and treat” approach for HPV E6/E7 mRNA testing. PLoS One, 5(9), e12724. Nakalembe, M., Makanga, P., Mubiru, F., Swanson, M., Martin, J., & Huchko, M. (2019). Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda. Infectious agents and cancer, 14, 1-10. Aydogan Kirmizi, D., Baser, E., Demir Caltekin, M., Onat, T., Sahin, S., & Yalvac, E. S. (2021). Concordance of HPV, conventional smear, colposcopy, and conization results in cervical dysplasia. Diagnostic Cytopathology, 49(1), 132-139. Kaya Terzi, N., & Yulek, O. (2024). Assessment of Cervicovaginal Smear and HPV DNA Co-Test for Cervical Cancer Screening: Implications for Diagnosis and Follow-Up Strategies. Diagnostics, 14(6), 611. Kittisiam, T., Chanpanitkitchot, S., Tangjitgamol, S., Srijaipracharoen, S., Manusirivithaya, S., Srisomboon, J., et al (2024). Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician-collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer. Asian Pacific Journal of Cancer Prevention: APJCP, 25(1), 211. World Health Organization. (2021). WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. World Health Organization. AMERICA PI. INTEGRATING HPV TESTING IN CERVICAL CANCER SCREENING PROGRAMS Tables Table 1. Socio-demographic Characteristics (n=257) Variables No. % Age (years) 30 – <40 117 45.5 40 – <50 98 38.1 ≥50 42 16.3 Mean ± SD. 40.75 ± 9.10 Median (Min. – Max.) 41.0 ( 30.0 – 69.0) IQR 32.0 – 47.0 Marital Status Married 150 58.4 Single 39 15.2 Divorced 22 8.6 Widowed 46 17.9 Education level None/primary 107 41.6 Secondary 103 40.1 Tertiary 47 18.3 Occupation Employed 67 26.1 Self employed 61 23.7 Unemployed 129 50.2 Parity Nulliparous 97 37.7 Para 1 and above 160 62.3 IQR: Inter quartile range SD: Standard deviation Table 2. HPV Status of participants (n=257) Discordance between PCR DNA and Rapid test No. % Rapid test results Positive 149 58.0 Negative 108 42.0 PCR 16 Positive 133 51.8 Negative 124 48.2 PCR 18 Positive 142 55.3 Negative 115 44.7 NON-16/18 Positive 59 23.0 Negative 198 77.0 Table 3. Discordance between rapid HPV test and PCR DNA (n=257) PCR VS RAPID TEST No. % Concordant 198 77.0 Discordant 59 23.0 Table 4. Accuracy of Rapid HR-HPV oncoprotein E6/E7 test compared to PCR DNA test for HR-HPV 16, 18, and NON-16/18 Tests AUC p 95% C.I Sensitivity Specificity PPV NPV Accuracy Rapid test results 0.992 <0.001 * 0.98 – 1.00 99.33 99.07 99.33 99.07 99.22 PCR 16 0.946 <0.001 * 0.92 – 0.98 89.26 100.0 100.0 87.10 93.77 PCR 18 0.977 <0.001 * 0.96 – 0.99 95.30 100.0 100.0 93.91 97.28 PCR NON-16/18 0.698 <0.001 * 0.64 – 0.76 39.60 100.0 100.0 54.55 64.98 AUC: Area Under a Curve p-value: Probability value CI: Confidence Intervals NPV: Negative predictive value PPV: Positive predictive value Additional Declarations No competing interests reported. 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07:36:46","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":274659,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity and specificity between rapid HR-HPV oncoprotein mRNA and PCR DNA tests\u003c/p\u003e","description":"","filename":"FIGURE2MANUSCRIPTRAPIDHPV.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6852002/v1/d91d2d21ebdc365008bab2dd.jpg"},{"id":85183346,"identity":"6c33d1bf-a3b3-4cb1-8279-7022f684bb9b","added_by":"auto","created_at":"2025-06-23 07:44:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1797172,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6852002/v1/5561e0fb-da40-4f89-9a86-f6cff08c7018.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnostic Accuracy of the Rapid Human Papillomavirus Oncoprotein E6/E7 Antigen Test for Cervical Cancer Screening in a Low-Resource Setting: A Cross-Sectional Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePersistent high-risk human papillomavirus (HR-HPV) is responsible for 95% of all cases of cervical cancer worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. In low- and middle-income countries, the prevalence of HR-HPV and the incidence of cervical cancer remain high due to limited access to preventive measures and treatment [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most of these countries lack acceptance of primary prevention measures and lack access to accurate and cost-effective screening methods [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The cervical HPV test, especially the polymerase chain reaction deoxyribonucleic acid (PCR DNA) test, has been acknowledged as the standard cervical cancer screening modality because of its high sensitivity and specificity. This test has offered a great opportunity to improve the effectiveness of cervical cancer screening [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The WHO global strategy has established three targets to be achieved by the year 2030 to position all countries on the pathway to eliminate this deadly and preventable disease [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, sub-Saharan Africa (SSA), the cradle of HR-HPV and cervical cancer, has been struggling to achieve the World Health Organization\u0026rsquo;s goal to eliminate cervical cancer through the prevention, screening, and treatment of premalignant cervical cancer lesions and early cervical cancer [1˗3].\u003c/p\u003e \u003cp\u003eTo date, studies have shown that laboratory tests for the detection of high-risk HR-HPV are more sensitive and reliable than conventional cytology and visual inspection using acetic acid and/or Lugol iodine [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The currently available evidence has shown that both the sensitivity and specificity of the high-risk HPV DNA screening test are less for adenocarcinoma [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], but very good for squamous cell carcinoma, except [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Despite its acknowledgement as the gold standard screening method, its high cost, sophisticated equipment that requires additional training, the need for electricity, the need for regular maintenance of the equipment, expensive reagents, and long turnaround time of up to 2 weeks limit HPV DNA testing in low- and middle-income countries (LMICs) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Economic assessments are relevant to support the decision to incorporate more cost-effective strategies for the screening and treatment of cervical cancer at LMICs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The challenges in LMICs are numerous, and the lower socioeconomic status (SES) of most women in those countries unfortunately affects their health care-seeking behaviour, as poor health care literacy compromises their compliance with medical advice and their understanding of the diagnosis of their health problems. For example, a positive HR-HPV test may increase anxiety among women, although HPV infections are transient in most women. The current WHO guidelines for the screening of cervical cancer in LMICs are challenged by limited resources, and thus follow-up after positive results are obtained at first screening can be difficult [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAccording to the WHO, several HPV tests are available: some HPV tests detect DNA, while other HPV tests detect the oncoprotein E6/E7 mRNA [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Tests that are currently commercially available and that are being used in some countries for cervical cancer screening include the Hybrid Capture 2 (Qiagen), CareHPV (Qiagen), Cobas HPV Test (Roche), Cervista (Hologic), Aptima HPV Assay (Hologic), BD HPV Assay (BD) and Xpert HPV (Cepheid) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In selecting which HPV test will be used in a given screening program, consideration should be given to the results of clinical trials, clinical validation of the test, and other operational and logistical aspects of the test and its requirements [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe carcinogenesis of the cervix is mediated by the HPV-E6 and E7 oncoproteins, which are biomarkers that are useful for managing women with positive screening results. To date, evidence has established that these 2 oncoproteins play a major role in promoting and maintaining cervical carcinogenesis, as they are overexpressed during cervical transformation [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The oncoprotein E6 plays a major role in cell immortalization, as it binds to the tumour suppressor protein p53, which is usually activated in normal cells in response to DNA damage. This binding degrades p53 and prevents the cell from undergoing apoptosis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. When the oncoprotein E7 interacts with host proteins, it binds to the cellular tumour suppressor pRb, which leads to its degradation, preventing it from inactivating transcription factors and promoting cell proliferation [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In addition, the overexpression of E6 and E7 leads to the accumulation of genetic errors in cells over time, which when combined with viral gene deregulation, drives invasive cancer [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Thus, oncoproteins E6 and E7 are interesting markers of persistent HR-HPV infection and associated precancerous lesions.\u003c/p\u003e \u003cp\u003eReaders may ask what the difference is between the test for the E6 and E7 oncoproteins and the HPV DNA genotype test in cervical cancer screening. The oncoproteins E6 and E7 differ according to HPV genotype. Thus, tests must target oncoproteins from diverse oncogenic types to ensure high sensitivity and specificity [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The clinical accuracy of E6 or E7 DNA and RNA assays has been demonstrated in several studies [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, few studies in sub-Saharan Africa have been conducted to determine the accuracy of rapid HR-HPV mRNA oncoprotein E6/E7 detection. To fill this gap, this study aimed to determine the diagnostic accuracy of the HR-HPV mRNA oncoprotein E6/E7 test in a low-resource setting as a cost-effective cervical cancer screening modality.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design, setting, and population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a cross-sectional study performed at Moi Teaching and Referral Hospital, the second-largest national hospital in Kenya. This multispecialty hospital, which serves a population of over 25 million people in Kenya, parts of Eastern Uganda, South Sudan, Northern Tanzania, and the Democratic Republic of the Congo, is known for its high-quality health care. In partnership with the Academic Model Providing Access to Health care (AMPATH), the hospital offers screening, prevention, and treatment for gynaecological cancers. Since screening for the cervical program started in 2009, hospitals and their satellites have essentially used visual inspection with acetic acid, and occasionally, Pap cytology and HPV PCR DNA testing. The government of Kenya approved and adopted the HPV PCR DNA test as the gold standard screening method for cervical cancer in 2018; however, the high cost of the test and other constraints previously mentioned have limited its implementation in rural areas.\u003c/p\u003e\n\u003cp\u003eIn November 2023, a feasibility study was conducted using rapid testing of HPV oncoproteins E6 and E7, Pap cytology, and PCR. This feasibility study enrolled 185 participants. Both samples collected by the patients and those collected by clinicians were used for rapid testing of HPV oncoproteins E6 and E7. For the current study, 257 participants were included. All women aged between 30 and 65 years who attended the family planning and dysplasia clinics at Moi Teaching and Referral Hospital within the study period and who provided informed consent to participate in this study were included. Considering the short period of data collection, pregnant women, women aged less than 30 years, and women with confirmed diagnoses of cervical cancer were excluded. Those who were menstruating were temporarily excluded until bleeding ceased. All eligible women were approached and given information about cervical cancer screening and the study, methods of sample collection, the two HR‒HPV tests, and the meaning of the results (negative and positive) before providing informed consent. Figure 1 illustrates the recruitment process for the participants.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe data collection was conducted by experienced and trained research assistants, including 2 registered nurses (RNs), 3 medical doctors, and 1 social worker. Written informed consent was obtained from each participant. Women who could not read or write were assisted by a social worker in the presence of either a relative or a social worker.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuestionnaire survey\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe research assistants (nurses and doctors) administered a questionnaire that was developed in English and translated into Kiswahili. The data included sociodemographic and clinical characteristics. The research assistants provided counselling to each study participant and explained the implications of an HR-HPV-positive result. Three to four weeks after the HPV sampling, the participants received results either through a message (those with negative results) or in person (those with positive results).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample collection for detection of the HPV oncoproteins\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;E6 and E7\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe eligible women were assisted by either the RN or the medical doctor during sample collection using the Delphi vaginal self-sampler (DVSS). All research assistants were trained for 3 months before the start of the study, and then, refresher training was performed 3 days before the enrolment of participants. The kits did not contain expired materials, and precautions were taken to avoid cross-contamination of the samples; a new specimen collection container was used for each sample. After the patient was placed on the gynaecological examination table and the speculum was inserted, the excess mucus discharge was removed from the cervix with a cotton ball and discarded. The DVSS was inserted, and the sample was collected according to the manufacturer\u0026rsquo;s instructions. This process was performed for each participant. The collected sample was immediately prepared for testing as described below.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV DNA PCR sample collection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe eligible women were assisted by either the RN or the medical doctor when HPV DNA was collected using an Evalyn Brush\u003csup\u003e\u0026reg;\u003c/sup\u003e (Evalyn Rovers Medical Devices BV, the Netherlands) for\u0026nbsp;HR‒HPV DNA tests. The Evalyn\u003csup\u003e\u0026reg;\u003c/sup\u003e Brush is validated for use in PCR-based assays, which ensures the highest number of valid samples across all age groups. In addition, the use of a dry sample (with no liquid in the mail) makes it compatible with the Cobas\u003csup\u003e\u0026reg;\u003c/sup\u003e 6800 or 4800 system for polymerase chain reaction (PCR).\u0026nbsp;The collected HR-HPV DNA\u0026nbsp;samples\u0026nbsp;were transported daily to the Lancet-Kenya laboratory, Eldoret branch, and were stored in the Department of Pathology at room temperature (approximately\u0026nbsp;19\u0026ndash;24 \u0026deg;C) for a maximum of 2 weeks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV oncoprotein E6 and E7 specimen testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe collected sample was prepared using a pipette (dropper). Eight (8) drops were extracted from the tube for each sample. Eight (8) drops of extraction buffer A were added to the extracted sample, and the mixture was shaken well. After 2 minutes, 8 drops of extraction buffer B were added to the sample, which was incubated with the buffer for 1 minute. Three drops (approximately 100 \u0026mu;l) were extracted from the tube to the sample well onto the cassette. For each prepared sample, the result was read within 15 minutes following extraction from the tube to the sample well onto the cassette. The result was positive when 2 coloured (red-like) bands appeared on the membrane (cassette): one band appeared in the control region (C), and another band appeared in the test region (T). In contrast, the result was negative when only one coloured band appeared in the control region, while the band in the test region (T) was not coloured. The appearance of a faint coloured band in the control region was reported as positive.\u003c/p\u003e\n\u003cp\u003eThe rapid test for HPV oncoproteins E6 and E7 is manufactured for the qualitative detection of the HR-HPV 16/18/13/45/52/58 E6 and E7 oncoproteins only, but without segregation, as in the HPV DNA PCR test.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV DNA specimen testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe samples collected were also transferred daily to Lancet Kenya, Eldoret branch, for testing. The samples were processed biweekly using the Cobas\u003csup\u003e\u0026reg;\u003c/sup\u003e 6800 system for HPV DNA polymerase chain reaction (PCR). This system detects the presence of 14 HR-HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). The results are automatically interpreted by the HPV DNA PCR test system and are displayed graphically on a controller monitor screen as either \u0026lsquo;positive\u0026rsquo; or \u0026lsquo;negative for a specific HR-HPV type [22, 23, 24, 25]. The samples were analysed by trained laboratory technicians from a certified laboratory, Cerba Lancet Kenya. This study did not receive ethics committee approval for a Pap test, which could have been impactful and useful.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical relevance of this study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study helps determine the clinical impact of using the rapid HR-HPV oncoprotein E6/E7 test, which is an affordable and accessible cervical cancer screening modality, and helps guide decision-making about whether to incorporate this test into routine practice in low-resource settings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eManagement of the results and future\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eplans\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;for participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe precaution of releasing positive results in a doctor\u0026rsquo;s office was adopted to reduce anxiety associated with such results. Appropriate counselling was provided to emphasize that HPV-positive results from the rapid HPV oncoprotein E6 and E7 test require confirmatory tests with HR-HPV PCR DNA. In addition, HR-HPV DNA PCR-positive results need to be paired with the results of another test\u0026mdash;cytology or with\u0026mdash;and patients should be referred for colposcopy and follow-up care [26, 27].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe statistical analyses were conducted using the statistical software package SPSS V.20.0 (Armonk, NY: IBM Corp.). Qualitative data are presented as numbers and percentages. The Kolmogorov‒Smirnov test was used to verify the normality of the distribution. The quantitative data are presented as ranges (minimums and maximums), means, standard deviations, medians, and interquartile ranges (IQRs).\u003c/p\u003e\n\u003cp\u003eStatistical analysis of the accuracy of the rapid HPV oncoprotein E6/E7 test quantified how well the test correctly identified individuals with or without a disease according to measures such as sensitivity, specificity, and predictive values. The rapid test reported the results as either positive or negative, whereas the HPV PCR DNA test quantitatively separated the results into 3 groups: HR-HPV 16, HR-HPV 18, and HR-HPV non-16/18. On the basis of the interpretation of the PCR DNA results, these results were reported as either positive or negative for the specific genotype mentioned above. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of HR-HPV in each test were calculated. A positive result was defined when both tests were positive or when either test was negative. The sensitivity of the tests refers to the proportion of individuals with human papillomavirus infection who were correctly identified by the test (true positives), whereas the specificity of the tests refers to the proportion of individuals without the disease who were correctly identified by the test (true negatives) [28]. The results of the two diagnostic tests were interpreted to determine whether the participants had or did not have high-risk human papillomavirus infection according to the predictive values (positive or negative). The probability that participants with positive test results were actually infected with HR-HPV was referred to as the positive predictive value, whereas the probability that those with negative results were actually negative was referred to as a negative predictive value [29].\u003c/p\u003e\n\u003cp\u003eFurthermore, the overall diagnostic ability of the test to provide an accurate diagnosis was assessed using the area under the receiver operating characteristic (ROC) curve (AUC) [30, 31]. The ROC curve results graphically displayed the effective sensitivity for each specificity for high-risk human papillomavirus infection. The significance of the results was judged at the 5% level.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eSociodemographic characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean age of the participants was 40.8 \u0026plusmn; 9.1 years, as described in Table 1. Women aged between 40 and 50 years accounted for 38.1% of all patients, while those aged between 30 and \u0026lt; 40 years accounted for 45.5%. With respect to the marital status of the participants, most were married women and widows and represented 58.4% and 17.9% of all patients, respectively. Participants with primary and secondary education levels were almost equally represented. More than half of the participants were unemployed (see Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV status\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of the participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWith respect to the HPV status of the participants, 58.0% reported positive results for rapid tests that used mRNA, whereas 42% of the participants tested negative. For the PCR test, 7.4% of the participants tested positive for high-risk HPV 16, whereas 3.1% tested positive for high-risk HPV 18. In addition, 33.5% of the participants tested positive for non-high-risk HPV 16/18 (see Table 2). Table 3 shows the concordance between the rapid oncoprotein E6/E7 and PCR DNA tests in 77% of the cases.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAccuracy of rapid HR-HPV oncoprotein\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;detection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 4 shows that the sensitivity of the rapid oncoprotein E6 and E7 test was 99.33% and that the specificity was 99.07%. In addition, the positive and negative predictive values were 99.33% and 99.07%, respectively. The accuracy of the rapid oncoprotein E6 and E7 test was 99.22%. These findings were statistically significant (p \u0026lt;0.001, 95% CI=0.98\u0026ndash;1.00), and the AUC for the rapid oncoprotein E6 and E7 test was 0.992.\u003c/p\u003e\n\u003cp\u003eThe accuracy of the HR‒HPV PCR DNA test was individually assessed according to the human papillomavirus genotypes, as summarized in Table 4 and graphically demonstrated in Figure 2. The sensitivity and specificity for HR-HPV 16 were 89.26% and 100.0%, respectively. In addition, the positive and negative predictive values for the HR-HPV 16 PCR DNA test were 100.0% and 87.10%, respectively. The accuracy of the HR-HPV 16 PCR DNA test was 93.77%, with an AUC of 0.946. This difference was statistically significant (p \u0026lt;0.001, 95% CI=0.92\u0026ndash;0.98). For HR-HPV 18, the sensitivity and specificity were 95.30% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 93.91%, respectively, with an estimated diagnostic accuracy of 97.28% and an AUC of 0.977. This difference was statistically significant (p\u0026lt;0.001, 95% CI=0.96\u0026ndash;0.99). With respect to the PCR DNA test for HR-HPV non-16/18, the sensitivity and specificity of the test were 39.60% and 100.0%, respectively, whereas the positive and negative predictive values were 100.0% and 54.55%, respectively. The accuracy of the PCR DNA test for HR-HPV non-16/18 was 64.98%, with an AUC of 0.698. This difference was statistically significant (p\u0026lt;0.001, 95% CI=0.64\u0026ndash;0.76).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe overall positive rate of the HR-HPV oncoproteins E6/E7 observed in the present study was lower (58.0% vs. 70%) than that reported in Brazil by Valen\u0026ccedil;a, J. E. C et al. (2016) [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] and the 100% positive rate reported in a Korean study [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In contrast with the current study, both the Brazilian and Korean studies were conducted on patients who were diagnosed with low-grade and high-grade squamous intraepithelial lesions. The three studies used HR-HPV tests targeting the E6 and E7 mRNAs using different kits with novel technologies. The current study used qualitative E6 and E7 tests, whereas the 2 previous studies used quantitative E6 and E7 mRNA tests [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] to identify the specific HR-HPV genotype. Although the qualitative E6 and E7 mRNA tests used could not specify the HR-HPV genotype, the tests were able to report positivity for the E6/E7 oncoproteins, while the PCR DNA test separated the results into the HPV 16, HPV 18, or non-HPV 16/18 groups. The low positivity rates reported in this study may be related to the grade of the cervical lesions (low grade), which is currently difficult to determine. Follow-up care with colposcopy or cytology and biopsy for those with positive test results is important. However, previous studies have shown that the mRNA positivity rate is increased in patients with more severe cervical intraepithelial lesions [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe sensitivity of the oncoprotein E6/E7 mRNA reported in this study was greater than that reported by Benevolo, M., and colleagues (2011) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], and recently, that by Downham, L., et al. (2024) [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In contrast to the current study findings, the other 2 studies were conducted under similar circumstances in patients who were diagnosed with cervical intraepithelial neoplasia (CIN) or abnormal cytology. In the first study, the sensitivity varied according to the severity of CIN. For example, Benevolo M. et al. reported an HPV mRNA sensitivity of 83% in atypical squamous cells of undetermined significance (ASCUS), 62% in low-grade squamous intraepithelial lesions (LSILs), and 67% in high-grade squamous intraepithelial lesions (HSILs) [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, the corresponding sensitivities in the same study were 99%, 91%, and 96% for the HR-HPV DNA PCR test [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In one recent systematic review, the pooled sensitivity of an enzyme-linked immunosorbent assay (ELISA) (100% vs. 18%) was reported, whereas the pooled sensitivity of a multiplex HPV serology assay was reported to be 16% [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], which is lower than the sensitivity reported for the rapid detection of HPV mRNA. As in the APTIMA mRNA study, the higher sensitivity compared with that in previous studies may be because the samples were collected by clinicians versus the patients.\u003c/p\u003e \u003cp\u003eIn the present study, the sensitivity of the HR-HPV PCR DNA test was low for the detection of HR-HPV 16 and 18 and extremely low for HR-HPV non-16/18 compared with the sensitivity of the rapid oncoprotein E6/E7 test. This is difficult to explain because the sensitivity of the diagnostic test is not influenced by the prevalence of the disease [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. In addition, PreTect HPV-Proofer was used to detect the mRNAs of the HPV oncoproteins E6 and E7, whereas the current study used the rapid HPV oncoprotein E6 and E7 mRNA test method. In the Aptima study [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e], the sensitivity was 96.3%, which was similar to what was reported in the current study. These findings indicate that mRNA oncoprotein tests are good cervical cancer screening modalities, especially in low- and middle-income countries.\u003c/p\u003e \u003cp\u003eIn this study, the specificity of the current rapid E6/E7 oncoprotein test was greater than that reported by Benevolo M. et al. [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. In the study by Benevolo and colleagues, low specificity was observed, especially for ASCUS and LSIL (63.2% vs. 82 and 76), while higher specificity was found for HSIL [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. The Pap test was not approved by the ethics committee for the current study, and thus any data comparison is difficult. One systematic review revealed that HPV16 and HPV18 oncoprotein E6 and E7 antibodies have high specificity but low sensitivity for detecting cases of cervical cancer or CIN2/3 precancerous lesions [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In the Aptima study, the specificity of the LSIL was 43.2%, which was lower than the specificity reported in the current study. In contrast, the specificity of the HR-HPV DNA PCR test was optimally greater, which supports the superiority of tests excluding false positivity, whereas the Aptima study reported a specificity of 85%. Although the specificity of the HR-HPV DNA PCR test was 100% in the current study, several studies have reported low specificity of the HR-HPV DNA test and high specificity for HR-HPV mRNA tests (specificity as low as 29%, 13%, and 4% for ASCUS, LSIL, and HSIL, respectively) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This is because high-risk HPV tests have low specificity in detecting high-grade cervical intraepithelial neoplasia (CIN2 or CIN3) [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe positive predictive value (PPV) in the current study was comparable to that reported in another HPV mRNA study (99% vs. 96%) [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e] and higher than that reported in yet another study, (80%) [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. However, the PPV reported in this previous study was exclusively for HSIL. The difference may be partially due to the different use purposes of HPV mRNA tests between the studies. The current study uses HPV mRNA tests as screening tests, whereas the other 2 studies used mRNA tests as triage tests to reduce the need for referrals for colposcopy. In the Ugandan study, the positive predictive value for the detection of any HR-HPV E6/E7 mRNA for the presence of CIN 2\u0026thinsp;+\u0026thinsp;was 8.2% [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e], which was lower than that reported with rapid HPV mRNA tests. In addition, the positive predictive value associated with the detection of HPV-16 mRNA was 15%, and that for the detection of HPV-18/45 mRNAs was 15% lower [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. In contrast to the current hospital-based study, the Ugandan study was a community-based screening study. However, the positive predictive value of the HPV DNA PCR test was reported to be 100% for HR-HPV 16 and 18. This finding contrasts with what was observed by Aydogan Kirmizi, D. et al. (2021), who reported a PPV of 66.7% for LSIL and 70.0% for HSIL [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], which is similar to what was reported by Kaya Terzi, N. (2021) [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, the negative predictive value was 100%, which is higher than the 91.9% recently reported by Kittisiam, T., et al. (2024) [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Few studies have been published on the negative predictive value of HPV DNA and mRNA.\u003c/p\u003e \u003cp\u003eThe findings from the present study revealed that the accuracy of the rapid HPV mRNA test was greater than that of the HPV DNA test (99.07% vs. 87.10% for HPV16, 93.03% for HPV18, and 54.55% for HR-HPV non-16/18). These results are similar to observations made by the WHO through the generation data group (GDG) regarding the accuracy of HPV mRNA tests vs. HPV DNA tests [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e]. In a recent systematic review conducted by Arbyn M. and colleagues [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], HPV mRNA tests, especially the APTIMA HPV assay, which targets the E6/E7 mRNA of HR-HPV, showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In contrast to APTIMA, the rapid HPV assay targeting E6/E7 of HR-HPV16/18 showed high sensitivity and specificity as a promising primary screening test. The differences between the APTIMA and the rapid HR-HPV screening tests include the following: APTIMA is a quantitative test with a turnaround of 3\u0026ndash;4 hours, which is similar to the GeneXpert HPV DNA tests, whereas the rapid HR-HPV 16/18 test is a qualitative test with a turnaround of 15 minutes.\u003c/p\u003e \u003cp\u003eThe performance of the rapid oncoprotein E6/E7 test as a screening modality is similar to that of the PCR DNA test. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows this result better, as the AUC values of the tests were interpreted and compared with those of the HR-HPV genotypes. The ROC curve shows that the rapid oncoprotein E6/E7 test is highly accurate. Mander and colleagues reported that a diagnostic test is useful when its sensitivity and specificity are greater than 50% [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Therefore, the integration of rapid oncoprotein E6/E7 tests as a cervical cancer screening modality in LMICs will positively impact the strategy of eliminating cervical cancer.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe high sensitivity and relative specificity of the rapid HR-HPV E6 and E7 mRNA test support its use for primary cervical cancer screening. However, women with positive HR-HPV results should be referred for colposcopy and further follow-up care. Large-scale and longitudinal studies are needed to validate the rapid detection of E6/E7 oncoproteins as a primary cervical cancer screening method at the community level.\u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Strengths and limitations","content":"\u003cul\u003e \u003cli\u003e \u003cp\u003eThis study demonstrated that the rapid HPV oncoprotein test is as accurate as the PCR DNA test for cervical cancer screening.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThe negative predictive value observed is comparable to that of the PCR DNA test.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThe inclusion of faint results increases the number of false-positive results.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eWomen with positive rapid HPV oncoprotein results should be referred for colposcopy.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eThis study did not receive ethics committee approval for the Pap test to be performed on the study participants.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eASCUS\u003c/strong\u003e: Atypical squamous cells of undetermined significance\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e: Area under the curve\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCIN\u003c/strong\u003e: Cervical intraepithelial neoplasia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDNA\u003c/strong\u003e: Deoxyribonucleic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPV\u003c/strong\u003e: Human papillomavirus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHR\u003c/strong\u003e: high-risk\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHSIL\u003c/strong\u003e: high-grade squamous intraepithelial lesions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLSIL\u003c/strong\u003e: low-grade intraepithelial lesions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003emRNA\u003c/strong\u003e: messenger RNA\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNPV\u003c/strong\u003e: negative predictive value\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePCR\u003c/strong\u003e: Ribonucleic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePPV\u003c/strong\u003e: positive predictive value\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRNA\u003c/strong\u003e: Ribonucleic acid\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eROC\u003c/strong\u003e: Receiver operating characteristic\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics approval and consent to participate\u003c/strong\u003e: This study received approval from the MTRH/MU-Institutional Research and Ethics Committee (IREC) under the approval number FAN: 0004670 and the National research permit number NACOSTI/P/24/33601.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial\u003c/strong\u003e: Not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eConsent was obtained during enrolment in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e: The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: None to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: No other funds were received.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contribution contributors\u003c/strong\u003e: All the authors reviewed the manuscript. Conceptualization, investigation, and methodology were\u0026nbsp;performed by the TKC, PPA, and MEW. Project administration and resources were performed by (KM, CEK, MK, BRM, OBE, NJN, MB, KK, KWK, MRM, AWK). Supervision, data curation, and formal analysis were\u0026nbsp;performed by PPA, IPM, TPK,\u0026nbsp;and\u0026nbsp;MEW.\u0026nbsp;Validation, visualization, and rewriting of the manuscript were performed by all\u0026nbsp;the\u0026nbsp;authors (TKC, PPA, MEW, KM, CEK, MK, BRM, OBE, NJN, MB, KK, KWK, MRM, AWK, IPM,\u0026nbsp;and\u0026nbsp;TPK).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e: We acknowledge the management of Moi Teaching and Referral Hospital for supporting the initiative of conducting this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eG\u0026Uuml;LTEKİN, M., Ramirez, P., Broutet, N., \u0026amp; Hutubessy, R. (2020). World Health Organization call for action to eliminate cervical cancer globally. International Journal of Gynecological Cancer, 30(4).\u003c/li\u003e\n \u003cli\u003eSantesso, N., Mustafa, R. A., Sch\u0026uuml;nemann, H. J., Arbyn, M., Blumenthal, P. D., Cain, J., et al. (2016). World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2\u0026ndash;3 and screen‐and‐treat strategies to prevent cervical cancer. International Journal of Gynecology \u0026amp; Obstetrics, 132(3), 252-258.\u003c/li\u003e\n \u003cli\u003eKutz, J. M., Rausche, P., Gheit, T., Puradiredja, D. I., \u0026amp; Fusco, D. (2023). Barriers and facilitators of HPV vaccination in sub-saharan Africa: a systematic review. BMC Public Health, 23(1), 974.\u003c/li\u003e\n \u003cli\u003eBoone, J. D., Erickson, B. K., \u0026amp; Huh, W. K. (2012). New insights into cervical cancer screening. Journal of gynecologic oncology, 23(4), 282.\u003c/li\u003e\n \u003cli\u003eRam\u0026iacute;rez, A. T., Valls, J., Baena, A., Rojas, F. D., Ram\u0026iacute;rez, K., \u0026Aacute;lvarez, R., et al (2023). Performance of cervical cytology and HPV testing for primary cervical cancer screening in Latin America: an analysis within the ESTAMPA study. The Lancet Regional Health\u0026ndash;Americas, 26.\u003c/li\u003e\n \u003cli\u003eChrysostomou, A. C., \u0026amp; Kostrikis, L. G. (2020). Methodologies of primary HPV testing currently applied for cervical cancer screening. Life, 10(11), 290.\u003c/li\u003e\n \u003cli\u003eBurd, E. M. (2003). Human papillomavirus and cervical cancer. Clinical microbiology reviews, 16(1), 1-17.\u003c/li\u003e\n \u003cli\u003eBhatla, N., \u0026amp; Singhal, S. (2020). Primary HPV screening for cervical cancer. Best Practice \u0026amp; Research Clinical Obstetrics \u0026amp; Gynaecology, 65, 98-108.\u003c/li\u003e\n \u003cli\u003eRizzo, A. E., \u0026amp; Feldman, S. (2018). Update on primary HPV screening for cervical cancer prevention. 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Cervical screening using HPV-DNA cytology in a low-income setting: an audit within a socio-economically deprived rural community in the Philippines. Journal of Global Health Reports, 7, e2023047.\u003c/li\u003e\n \u003cli\u003eCasas, C. P. R., Albuquerque, R. D. C. R. D., Loureiro, R. B., Gollner, A. M., Freitas, M. G. D., Duque, G. P. D. N., et al (2022). Cervical cancer screening in low-and middle-income countries: A systematic review of economic evaluation studies. Clinics, 77, 100080.\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. (2021). WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention: use of mRNA tests for human papillomavirus (HPV). World Health Organization.\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. (2020). WHO technical guidance and specifications of medical devices for screening and treatment of precancerous lesions in the prevention of cervical cancer. World Health Organization.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMalla, R., \u0026amp; Kamal, M. A. (2021). E6 and E7 oncoproteins: Potential targets of cervical cancer. Current Medicinal Chemistry, 28(39), 8163-8181.\u003c/li\u003e\n \u003cli\u003eAraldi, R. P., Sant\u0026rsquo;Ana, T. A., M\u0026oacute;dolo, D. G., de Melo, T. C., Spadacci-Morena, D. D., de Cassia Stocco, R., et al (2018). The human papillomavirus (HPV)-related cancer biology: An overview. Biomedicine \u0026amp; pharmacotherapy, 106, 1537-1556.\u003c/li\u003e\n \u003cli\u003eBoccardo, E., Manzini Baldi, C. V., Carvalho, A. F., Rabachini, T., Torres, C., Barreta, L. A., et al (2010). Expression of human papillomavirus type 16 E7 oncoprotein alters keratinocytes expression profile in response to tumor necrosis factor-\u0026alpha;. Carcinogenesis, 31(3), 521-531.\u003c/li\u003e\n \u003cli\u003eYeo-Teh, N. S., Ito, Y., \u0026amp; Jha, S. (2018). High-risk human papillomaviral oncogenes E6 and E7 target key cellular pathways to achieve oncogenesis. International journal of molecular sciences, 19(6), 1706.\u003c/li\u003e\n \u003cli\u003eMcBride, A. A., \u0026amp; Warburton, A. (2017). The role of integration in oncogenic progression of HPV-associated cancers. PLoS pathogens, 13(4), e1006211.\u003c/li\u003e\n \u003cli\u003eArbyn, M., Simon, M., Peeters, E., Xu, L., Meijer, C. J., Berkhof, J., et al (2021). 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clinical Microbiology and Infection, 27(8), 1083-1095.\u003c/li\u003e\n \u003cli\u003eSaville, M., Sultana, F., Malloy, M. J., Velentzis, L. S., Caruana, M., Ip, E. L., et al (2019). Clinical Validation of the cobas HPV Test on the cobas 6800 System for the Purpose of Cervical Screening. Journal of Clinical Microbiology, 57(2), 10-1128.\u003c/li\u003e\n \u003cli\u003eSundstr\u0026ouml;m, K., Lamin, H., \u0026amp; Dillner, J. (2021). Validation of the cobas 6800 human papillomavirus test in primary cervical screening. PLoS One, 16(2), e0247291.\u003c/li\u003e\n \u003cli\u003eFrayle, H., Gori, S., Rizzi, M., Graziani, B. N., Vian, E., Giorgi Rossi, P., et al (2019). HPV testing for cervical cancer screening: technical improvement of laboratory logistics and good clinical performance of the cobas 6800 in comparison to the 4800 system. BMC Women\u0026apos;s Health, 19, 1-7.\u003c/li\u003e\n \u003cli\u003eMutombo, A. B., Benoy, I., Tozin, R., Bogers, J., Van Geertruyden, J. P., \u0026amp; Jacquemyn, Y. (2019). Prevalence and distribution of human papillomavirus genotypes among women in Kinshasa, the Democratic Republic of the Congo. Journal of Global Oncology, 5, 1-9.\u003c/li\u003e\n \u003cli\u003ePolman, N. J., Veldhuijzen, N. J., Heideman, D. A., Snijders, P. J., Meijer, C. J., Berkhof, J. (2019). Management of HPV‐positive women in cervical screening using results from two consecutive screening rounds. 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Y., Lee, D., Kim, S., Choi, Y., et al (2014). Performance of HPV E6/E7 mRNA RT-qPCR for screening and diagnosis of cervical cancer with ThinPrep\u0026reg; Pap test samples. Experimental and Molecular Pathology, 97(2), 279-284.\u003c/li\u003e\n \u003cli\u003eBenevolo, M., Vocaturo, A., Caraceni, D., French, D., Rosini, S., Zappacosta, R., et al (2011). Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test. Journal of clinical microbiology, 49(7), 2643-2650.\u003c/li\u003e\n \u003cli\u003eArbyn, M., Martin‐Hirsch, P., Buntinx, F., Van Ranst, M., Paraskevaidis, E., \u0026amp; Dillner, J. (2009). Triage of women with equivocal or low‐grade cervical cytology results: a meta‐analysis of the HPV test positivity rate. Journal of cellular and molecular medicine, 13(4), 648-659.\u003c/li\u003e\n \u003cli\u003eDownham, L., Jaafar, I., Rol, M. L., Nyawira Nyaga, V., Valls, J., Baena, A., et al (2024). Accuracy of HPV E6/E7 oncoprotein tests to detect high-grade cervical lesions: a systematic literature review and meta-analysis. British Journal of Cancer, 130(4), 517-525.\u003c/li\u003e\n \u003cli\u003eSingini, M. G., Singh, E., Bradshaw, D., Ramaliba, T., Chen, W. C., Motlhale, M., et al (2023). Usefulness of high‐risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer: A systematic review and meta‐analysis. Journal of medical virology, 95(1), e27900.\u003c/li\u003e\n \u003cli\u003eRatnam, S., Coutlee, F., Fontaine, D., Bentley, J., Escott, N., Ghatage, P., et al (2011). Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer. Journal of Clinical Microbiology, 49(2), 557-564.\u003c/li\u003e\n \u003cli\u003eKim, M. A., Oh, J. K., Chay, D. B., Park, D. C., Kim, S. M., Kang, E. S., et al (2010). Prevalence and seroprevalence of high-risk human papillomavirus infection. Obstetrics \u0026amp; Gynecology, 116(4), 932-940.\u003c/li\u003e\n \u003cli\u003eValen\u0026ccedil;a, J. E. C., Gon\u0026ccedil;alves, A. K., Silva, I. D. C. G. D., Eleut\u0026eacute;rio Junior, J., Silva, T. T. D., Bruneska, D., et al (2016). High risk HPV E6/E7 oncoprotein expression in women with high grade squamous intraepithelial lesion. Revista Brasileira de Ginecologia e Obstetr\u0026iacute;cia, 38, 154-159.\u003c/li\u003e\n \u003cli\u003eCuzick, J., Arbyn, M., Sankaranarayanan, R., Tsu, V., Ronco, G., Mayrand, M. H., et al (2008). Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries. Vaccine, 26, K29-K41.\u003c/li\u003e\n \u003cli\u003eCuzick, J., Clavel, C., Petry, K. U., Meijer, C. J., Hoyer, H., Ratnam, S., et al (2006). Overview of the European and North American studies on HPV testing in primary cervical cancer screening. International journal of cancer, 119(5), 1095-1101.\u003c/li\u003e\n \u003cli\u003eS\u0026oslash;rbye, S. W., Fismen, S., Gutteberg, T., \u0026amp; Mortensen, E. S. (2010). Triage of women with minor cervical lesions: data suggesting a \u0026ldquo;test and treat\u0026rdquo; approach for HPV E6/E7 mRNA testing. PLoS One, 5(9), e12724.\u003c/li\u003e\n \u003cli\u003eNakalembe, M., Makanga, P., Mubiru, F., Swanson, M., Martin, J., \u0026amp; Huchko, M. (2019). Prevalence, correlates, and predictive value of high-risk human papillomavirus mRNA detection in a community-based cervical cancer screening program in western Uganda. Infectious agents and cancer, 14, 1-10.\u003c/li\u003e\n \u003cli\u003eAydogan Kirmizi, D., Baser, E., Demir Caltekin, M., Onat, T., Sahin, S., \u0026amp; Yalvac, E. S. (2021). Concordance of HPV, conventional smear, colposcopy, and conization results in cervical dysplasia. Diagnostic Cytopathology, 49(1), 132-139.\u003c/li\u003e\n \u003cli\u003eKaya Terzi, N., \u0026amp; Yulek, O. (2024). Assessment of Cervicovaginal Smear and HPV DNA Co-Test for Cervical Cancer Screening: Implications for Diagnosis and Follow-Up Strategies. Diagnostics, 14(6), 611.\u003c/li\u003e\n \u003cli\u003eKittisiam, T., Chanpanitkitchot, S., Tangjitgamol, S., Srijaipracharoen, S., Manusirivithaya, S., Srisomboon, J., et al (2024). Clinical Performance of Self-collected Specimen HPV-DNA vs Clinician-collected Specimen HPV-mRNA to Detect High-risk HPV and High-grade Cervical Lesions and Cancer. Asian Pacific Journal of Cancer Prevention: APJCP, 25(1), 211.\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. (2021). WHO guidelines for screening and treatment of precancerous lesions for cervical cancer prevention. World Health Organization.\u003c/li\u003e\n \u003cli\u003eAMERICA PI. INTEGRATING HPV TESTING IN CERVICAL CANCER SCREENING PROGRAMS\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Socio-demographic Characteristics (n=257)\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e30 \u0026ndash; \u0026lt;40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e45.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e40 \u0026ndash; \u0026lt;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u0026ge;50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e16.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 189px;\"\u003e\n \u003cp\u003e40.75 \u003cspan dir=\"RTL\"\u003e\u0026plusmn;\u003c/span\u003e 9.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eMedian (Min. \u0026ndash; Max.)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 189px;\"\u003e\n \u003cp\u003e41.0 (\u003cspan dir=\"RTL\"\u003e30.0\u003c/span\u003e \u003cspan dir=\"RTL\"\u003e\u0026ndash;\u003c/span\u003e 69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 189px;\"\u003e\n \u003cp\u003e32.0 \u003cspan dir=\"RTL\"\u003e\u0026ndash;\u003c/span\u003e 47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMarital Status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eMarried\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e58.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSingle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eDivorced\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 208px;\"\u003e\n \u003cp\u003eWidowed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation level\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNone/primary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e41.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSecondary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e40.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eTertiary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e18.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOccupation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eEmployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eSelf employed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e23.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eUnemployed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e50.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNulliparous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e37.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003ePara 1 and above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e62.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eIQR: \u003cstrong\u003eInter quartile range\u003c/strong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;SD: \u003cstrong\u003eStandard deviation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. \u0026nbsp;HPV Status of participants (n=257)\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiscordance between PCR DNA and Rapid test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRapid test results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e58.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e42.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR 16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e51.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e48.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR 18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e55.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e44.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNON-16/18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e23.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e77.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eTable 3. Discordance between rapid HPV test and PCR DNA (n=257)\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 208px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR VS RAPID TEST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eConcordant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e77.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 208px;\"\u003e\n \u003cp\u003eDiscordant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e23.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. \u0026nbsp; Accuracy of Rapid HR-HPV oncoprotein E6/E7 test compared to \u0026nbsp;PCR DNA test for HR-HPV 16, 18, and NON-16/18\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"626\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Tests\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% C.I\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNPV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAccuracy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRapid test results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e0.98 \u0026ndash; 1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e99.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e99.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e99.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e99.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e99.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR 16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.946\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e0.92 \u0026ndash; 0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e89.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e87.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e93.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR 18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.977\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e0.96 \u0026ndash; 0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e95.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e93.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e97.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePCR NON-16/18\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.698\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e0.64 \u0026ndash; 0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e39.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e54.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 51px;\"\u003e\n \u003cp\u003e64.98\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eAUC: Area Under a Curve \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; p-value: Probability value\u003c/p\u003e\n\u003cp\u003eCI: Confidence Intervals\u003c/p\u003e\n\u003cp\u003eNPV: Negative predictive value \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; PPV: Positive predictive value\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Oncoproteins E6 and E7, diagnostic accuracy, mRNA, sensitivity and specificity, positive predictive value, negative predictive value","lastPublishedDoi":"10.21203/rs.3.rs-6852002/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6852002/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Persistent high-risk human papillomavirus is responsible for 95% of all cases of cervical cancer worldwide. Screening for high-risk genotypes has been acknowledged as the gold standard for the elimination of cervical cancer. However, most low- and middle-income countries have limited access to this screening method because ofa lack of adequate sustainable resources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This study aimed to compare the diagnostic accuracy of the rapid high-risk human papillomavirus 16/18 oncoprotein E6/E7 antigen test to that of the polymerase chain reaction (PCR) deoxyribonucleic acid test among women who presented to family planning and dysplasia clinics at Moi Teaching and Referral Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This was a cross-sectional study performed between February and July 2024 to compare the diagnostic accuracy of the rapid high-risk human papillomavirus 16/18 oncoprotein E6/E7 antigen test to that of the polymerase chain reaction deoxyribonucleic acid test among women who underwent cervical cancer screening at Moi Teaching and Referral Hospital. Two hundred and fifty-seven (257) women aged 30 years and older were randomly selected for this study. A cervical swab was obtained from all participants for human papillomavirus polymerase chain reaction deoxyribonucleic acid testing, followed by cervical sample collection using the Delphi vaginal self-sampler for the rapid human papillomavirus oncoprotein E6/E7 antigen test. To achieve the objective of the study, sensitivity, specificity, positive predictive value, and negative predictive value were measured. Data on sociodemographicand clinical characteristics were collected and analysed. The significance of the data was set at a two-tailed p\u0026lt;0.05. The chi-squaretest was used to compare categorical variables. Fisher’s exact test or the Monte Carlo correction was used for the chi-square analysis when more than 20% of the cells had an expected count \u0026lt;5.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: The sensitivity of the rapid oncoprotein E6 and E7 test was 99.33%, and the specificity was 99.07%. In addition, the positive predictive value and negative predictive value were 99.33% and 99.07%, respectively. Furthermore, the accuracy of the rapid oncoprotein E6/E7 test was 99.22%. These findings were statistically significant (p \u0026lt;0.001, 95% CI=0.98–1.00), and the AUC for the rapid oncoprotein E6/E7 test was 0.992.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: The accuracy of the rapid high-risk human papillomavirus mRNA oncoprotein E6/E7 antigen test is as good as that of the polymerase chain reaction deoxyribonucleic acid test for cervical cancer screening in low-resource settings.\u003c/p\u003e","manuscriptTitle":"Diagnostic Accuracy of the Rapid Human Papillomavirus Oncoprotein E6/E7 Antigen Test for Cervical Cancer Screening in a Low-Resource Setting: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-23 07:20:41","doi":"10.21203/rs.3.rs-6852002/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-30T08:03:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-28T14:13:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"153544282333531882669737178912249131202","date":"2025-09-17T11:00:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-30T06:07:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118143085087457009885935120638789710113","date":"2025-07-18T00:38:40+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-18T01:15:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-11T01:38:04+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-11T01:37:57+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-06-09T07:47:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5126cebf-27b1-47b2-afcd-d005715ae897","owner":[],"postedDate":"June 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-11T11:23:10+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-23 07:20:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6852002","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6852002","identity":"rs-6852002","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}