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Simple Summary: Cervical cancer is the fourth most common cancer in women worldwide, with HPV being a prevalent cause. Recent automated signal detection methods in ISH assays have shown promise for detecting HPV DNA in cervical tissue. This study compared an ISH probe (Inform HPV II and III) to PCR assays in cervical tissue samples with varying degrees of cervical intraepithelial neoplasia (CIN) and normal cervix tissue. Findings indicated a significant association between ISH III levels and HPV outcomes; patients with positive outcomes had lower ISH III levels (MD = −7961.82, p = 0.005). However, automatic signal detection for ISH is limited in cervical tissue, making genotyping-based HPV testing more effective, as it allows for larger sample collection. ISH results should be interpreted alongside clinical history and morphology. Background: Cervical cancer is fourth the most common cancer in women worldwide. Due to the prevalence of human papillomavirus (HPV) in the population (80–90%), scientists are likely to discover even more associations of this pathogen with other diseases in the future. In recent years, In Situ Hybridization (ISH) assays that use automated signal-detecting methods in formalin-fixed, paraffin-embedded (FFPE) cervical tissue, such as the enzyme-categorized signal-detecting system, have shown a higher sensitivity. Objectives and Methods: To evaluate automatic signal detection of ISH assay for detecting HPV DNA, we compared the ability of an ISH probe, Inform HPV II and III (Ventana Medical Systems, Tucson, AZ), to that of PCR assays to detect HPV DNA in cervical tissue specimens with cervical intraepithelial neoplasia (CIN; CIN 1, 28 cases; CIN 2, 22 cases; and CIN 3, 20 cases) and normal cervix (2 cases). Results: Our findings showed a significant relation was confirmed between ISH III level and HPV outcome (positive/negative). Patients with positive HPV outcomes had significantly lower ISH III levels, MD = −7961.82 CI95 [−17,230.00; −199.21], p = 0.005. Conclusions: Automatic signal detection of ISH assay is not particularly applicable to cervical tissue material. A more useful method of confirming the presence of HPV in the cervix is the HPV test with genotyping, as it allows for collecting a larger amount of material from the cervical disc and canal. The interpretation of a positive or negative ISH test must be guided in the context of clinical history and morphology. [ABSTRACT FROM AUTHOR]

Simple Summary: This research explores non-invasive methods for detecting Human Papillomavirus (HPV) in patients with oral squamous cell carcinoma (OSCC). The study compares two self-collection techniques, oral rinse vs. salivary sponge, to determine their effectiveness in identifying HPV DNA. Results from 26 patients indicated that the salivary sponge method was more accurate and sensitive compared to the oral rinse. This finding suggests that a salivary sponge may be a superior option, especially for patients with functional limitations caused by OSCC. Our research could lead to improved non-invasive diagnostic tools for HPV in clinical settings. Background/Objectives: Human Papillomavirus (HPV) is a significant etiological factor in the development of oropharyngeal carcinogenesis. The detection of HPV in oral squamous cell carcinoma (OSCC) could be also crucial for diagnosis, prognosis, and treatment planning. This study compares the efficacy and accuracy of two non-invasive sampling methods, oral rinse, and oral sponge, in detecting HPV DNA in patients with OSCC. Methods: Twenty-six patients with histologically confirmed OSCCs were recruited (M/F = 15/11; mean age 68.6). From each patient, two self-collected oral specimens, in the form of an oral rinse and a salivary sponge (i.e., LolliSponge), were collected, and subsequently processed, utilizing INNO-LiPA HPV Genotyping Extra II for HPV DNA detection; Results: Oral sponge detection showed high specificity (100%), sensitivity (85.7%), and accuracy (96.2%) compared to the oral rinse sampling, also demonstrating an area AUC for its diagnostic performance significantly greater than 0.5 (0.93 vs. 0.5, p < 0.0001). Conclusions: This study supports that oral sponge sampling offers valuable non-invasive alternatives for HPV detection in patients with OSCC, with the potentiality to facilitate saliva sampling in patients that may exhibit functional deficit due to OSCC. Further research is recommended to validate these findings in larger cohorts and to explore the integration of these methods into routine clinical practice for the management of HPV-related OSCC. [ABSTRACT FROM AUTHOR]

Background: The detection of human papillomavirus (HPV) has several implications in the diagnostic work-up and management of oropharyngeal squamous cell carcinoma (OPSCC). The choice of HPV detection assay and testing algorithms differ across institutions and vary in cost, detection targets, technical feasibility, and turnaround time. In this study, we aimed to validate the VisionArray® HPV Chip for formalin-fixed and paraffin-embedded (FFPE) samples of OPSCC using the previously applied standard pan-HPV DNA PCR assay as a reference. Methods: The validation cohort consisted of FFPE tissue samples from patients previously diagnosed with HPV DNA-positive OPSCC (n = 80), HPV DNA-negative OPSCC (n = 21), and a benign group of tumor samples consisting of Warthin’s tumors (n = 20) and branchial cleft cysts of the lateral neck (n = 14). All samples were tested with p16 immunohistochemistry, pan-HPV DNA PCR, and the VisionArray® HPV Chip. Results: The overall sensitivity and specificity of the VisionArray® HPV Chip assay were 100% [95% CI 95.5%; 100.0%] and 96.3% [95% CI 87.3%; 99.6%] and the positive predictive value and negative predictive value were 97.6% [95% CI 91.5%; 99.7%] and 100% [95% CI 93.2%; 100%], respectively. Conclusions: The VisionArray® HPV Chip assay can be recommended for high-risk HPV testing in FFPE tissue samples from OPSCC, providing both a fast and simultaneous genotyping for 41 clinically relevant HPV types. [ABSTRACT FROM AUTHOR]

Various clinico-pathological factors play role in the papilloma proliferation and pathogenesis of Recurrent respiratory papillomatosis (RRP). However, it is not known if they are directly responsible for malignant transformation of these papillomas or not. We did this study to elucidate any such association. The most recent debrided tissue of RRP in 20 patients was evaluated for p16 expression, VEGF estimation (tissue expression and serum levels), and tissue HPV DNA concentration. The final histopathology results were then correlated with these pathological factors and with clinical factors like duration of illness, age of onset of symptoms, extent of disease, etc. Squamous papilloma was seen in 60%, dysplasia in 25%, and squamous cell carcinoma (SCC) in 15% of the patients. Positive immunostaining for p16 (staining in ≥70% of tumor cells) was seen only in one case, which was SCC. There was no statistically significant difference between p16 expression, tissue VEGF expression, serum VEGF levels, and tissue HPV DNA in any of the histological groups. The mean age of disease onset was significantly higher in patients with SCC (p = 0.03). A significantly higher number of patients with dysplasia had tracheobronchial involvement (p = 0.022). We concluded that no single pathological factor is solely responsible for development of malignancy in RRP, whereas clinical factors like tracheobronchial involvement and age of onset may contribute to development of dysplasia or carcinoma. [ABSTRACT FROM AUTHOR]

There are currently several validated HPV tests. However, longitudinal data which spans appropriate age ranges, as well as evaluation of potential screening algorithms are necessary for screening programmes choice of test. The objective of our study was to evaluate the performance of HPV mRNA and HPV DNA testing, including partial genotyping, in routine cervical screening. As part of the CERVIVA HPV Primary Screening Study, ThinPrep samples from 10 150 women were tested for HPV mRNA using the Aptima HPV assay and HPV DNA using the Cobas 4800 HPV test. HPV mRNA‐positive women were further assessed with the Aptima genotyping assay for HPV 16/18/45. Baseline cytology and prospective follow‐up data were collected. The performance of the two tests was examined over 42 months (to date). HPV mRNA demonstrated equivalent sensitivity to HPV DNA testing for detection of CIN2+ (93.2% [92.4‐93.9] vs 92.8% [92.0‐93.6], respectively) and CIN3+ (94.6% [93.8‐95.3] vs 94.6% [93.8‐95.3]). HPV mRNA testing had significantly higher specificity compared to HPV DNA for detection of CIN2+ (84.0% [83.5‐84.5] vs 80.8% [80.2‐81.4], respectively) and CIN3+ (88.44% [88.2‐88.6] vs 85.62 [85.4‐85.9]). The proportion of CIN2+ and CIN3+, over 3 years (42 months), in HPV‐negative women was comparable for both RNA (0.20% and 0.10%) and DNA (0.22% and 0.11%). Genotyping data was comparable across both assay platforms. In the context of HPV primary screening HPV mRNA testing has potential to reduce triage tests and follow‐up tests at 12 months compared to DNA testing, with no significant difference in detection of CIN2+ and CIN3+. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is considered the commonest viral cause of sexually transmitted infections. The impact of social distance measures due to Covid-19 pandemic on HPV spread is unknown. Therefore, this study has analyzed the seven-year trend of HPV prevalence in all patients tested for HPV DNA at the Microbiology and Virology Unit at Bari Policlinico. Moreover, the HPV prevalence in 2020 has been compared with the previous year ones in order to evaluate the consequences of lockdown and social distancing measures on transmission risks. From 2013 to 2020, we retrospectively analyzed 64 anal swabs, 418 biopsies, 5925 cervical-vaginal swabs, 512 cervical swabs, 104 gland swabs, 154 oral swabs, 21 seminal fluids and 503 urethral swabs. HPV DNA detection was initially performed using nested-polymerase chain reaction (PCR) and subsequently multiplex real-time PCR assay. All statistical tests were carried out by the open-source environment R 4.0.3 (R Core Team). The data were analyzed according to yearly positivity rates, temporal trend and prevalence of HPV genotypes (HPV-6, HPV-11, HPV-16, HPV-18, high risk and low risk) by age category and sex. The number of patients increased steadily from 2016 to 2019 and then decreased in 2020. There were significant differences in prevalence between females and males for HPV-6 (6.16% in females Vs 30.80% in males), HPV-11 (0.82% Vs 7.16%) and HPV-16 (7.77% Vs 5.01%). The prevalence of HPV-6 and HPV-11 significantly increased in 2020 compared to 2013–2019 (15.72% Vs 8.52 and 3.18% Vs 1.44%). On the contrary, the overall prevalence of HPV DNA remained constant in 2020 (52.84% Vs 48.44%). Over time, the prevalence of HPV DNA (Coefficient=-0.020, p-value = 0.036) and particularly high-risk genotypes (Coefficient=-0.030, p-value = 0.005) decreased in females, while low-risk genotypes (Coefficient = 0.141, p-value= < 0.001) and the prevalence of HPV DNA increased in males (Coefficient = 0.068, p-value = 0.008). During the pandemic, the number of screened patients declined, although HPV prevalence compared to 2013–2019 remained constant or increased as in the case of low-risk genotypes. It can be assumed that the reduction of the screening coverage favored the emerging of the more symptomatic low-risk infections. In conclusion, nonpharmaceutical interventions due to Covid-19 pandemic did not reduce the risk of HPV infection but it likely caused a decrease in access to health services resulting in an increased risk of undiagnosed HPV. To decrease the impact of Covid-19 pandemic on the general population, several measures of social distancing were worldwide implemented potentially affecting sexual behaviors. Evaluating the impact of the social distancing measures on the risk of sexually transmitted infections, the published studies reached contradictory results showing the absence of a common epidemiological trend. The overall prevalence of HPV and some of its genotypes among female and male patients did not decrease in 2020 compared to the years 2013–2019. The risk of the HPV infection was not affected by the social distancing measures. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is a common malignancy causing cancer-related deaths worldwide. Evidence suggests that adequate screening can reduce cervical cancer-related deaths. Screening for cervical cancer can be done using Visual Inspection of Acetic Acid (VIA), HPV DNA and cytology. The economic burden of cancer patients is substantial ranging from US$8,066 to 22,888 per patient. Health cost effectiveness was comparative in the analysis of costs and consequences for the three screening methods. VIA is the most cost-effective primary screening test for cervical cancer. Purpose: To review the research results of a full economic evaluation to encourage the specific cervical cancer screening methods used to enhance the detection of precancerous lesions in women's cervix. Method: This systematic review used the PRISMA ScR framework with a literature search using 3 databases, namely Pubmed, Wiley, and Google Scholar, with years of publication from 2009 – 2023. The data that has been obtained is carried out by critical appraisal using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results: Based on the search for 3,973 selected articles, 7 match the inclusion criteria. This systematic review discovered three major themes: the utility value of health status, cost and analysis. Conclusion: The most cost-effective cervical cancer screening is by VIA. HPV DNA and pap smear based cytology techniques have been reported to show high sensitivity and specificity respectively including being expensive and resource intensive. In contrast the VIA technique has moderate sensitivity and specificity but is less expensive Various developed countries have used Pap or HPV DNA cytology tests as the main screening method, which can lead to a 50-70% reduction in cervical cancer incidence, while in developing countries using VIA tests as a cervical cancer screening method.

Cervical cancer remains a leading cause of cancer related morbidity and mortality in low/ low-middle income countries. Lack of screening is the leading cause of cases being diagnosed in advanced stages and screening is still opportunistic in a majority of these countries. Hospital visits during pregnancy provides a window of opportunity to screen these susceptible women and reduce the burden of disease. Screening women during pregnancy is not practiced widely due to concerns of pregnancy loss, bleeding and a lack of clear information among patients as well as healthcare professionals. [ABSTRACT FROM AUTHOR]

Purpose: The distribution of human papillomavirus (HPV) varies geographically, and each country is making its screening and vaccination program. This study questioned the need for colposcopy for HPV types other than HPV 16 and 18, and the need for cytology incorporated into HPV testing. Methods: 1043 consecutive patients referred for colposcopy are included in this retrospective study. Logistic regression analysis, ANOVA, and Pearson's correlation were used for statistical analysis. The value of p < 0.05 was considered statistically significant. Results: HPV 16 was the most common HPV type referred, followed by HPV 18, 52, 51, and 31, respectively. HPV 16 tends to be positive in younger patients than other HPV types (p < 0.05). Only HPV 16 (OR: 1.41, 1.06–1.88 95% CI) and HPV 33 (OR: 2.23; 1.06–4.64 95% CI) (p < 0.05) had significant prediction for CIN 2 + lesions. In patients with only a cytological abnormality, cytological abnormality with single other high-risk (hr) HPV (without HPV 16 or 18) or double other hrHPV positivity but without HPV 16 and 18 infections, we detected 159 (19%) CIN 2 + lesions. Conclusion: HPV 33 may be implemented in hrHPV screening protocols for direct colposcopy referral as well as HPV 16 and HPV 18 in specific regions. If we had opted for HPV-based screening only for HPV 16 and 18 without cytology, 19% of all CIN 2 + lesions would have been missed. HPV-based screening only with HPV 16 and 18 may not be feasible. Nonavalent vaccines should be considered for the vaccination of specific populations. [ABSTRACT FROM AUTHOR]

Simple Summary: Dynamics in global health adaptations to the SARS-CoV-2 pandemic culminated in a unique momentum to reform cervical screening by reinforcing self-sampling implementation. Aside from catch-up screening, self-sampling has established a continuing role in increasing cervical cancer screening uptake and scaling coverage globally. Thus, self-sampling has evolved as a key pillar of the ambitious global strategy of the WHO to eliminate cervical cancer. By providing opportunities and screening alternatives for women and by lowering the barriers to screening participation, self-sampling may ultimately reduce national, racial and social health disparities in cervical cancer rates. Identifying and reaching women at higher risk for cervical cancer is all-important for achieving the ambitious endpoints set in 2020 by the WHO for global cervical cancer control by 2030. HPV-based (vaginal) self-sampling (SS) represents a cost-effective screening strategy, which has been successfully implemented during the last decade both in affluent and constrained settings. Among other advantages, SS strategies offer convenience, diminished costs, flexibility to obtain a sample in the office or home, avoiding a pelvic exam and uncomfortable appointment with a healthcare professional, as well as social and cultural acceptability. SS implementation has been globally boosted during the COVID-19 pandemic. In pragmatic terms, social distancing, local lockdowns, discontinuation of clinics and reallocation of human and financial resources challenged established clinician-based screening; self-collection strategies apparently surpassed most obstacles, representing a viable and flexible alternative. With time, sufficient reassuring data has accumulated regarding specially designed SS devices, aspects of sample preparation, transport and storage and, importantly, optimization of validated PCR-based HPV testing platforms for self-collected specimens. Suboptimal rates of clinical follow-up post-SS screening, as well as overtreatment with reliance solely on molecular assays, have both been documented and remain concerning. Therefore, effective strategies are still required to ensure linkage to follow-up testing and management following positive SS results by trained health professionals with knowledge of HPV biology and management algorithms. Because of the prolonged SS screening intervals, implementation data are limited regarding subsequent screening rounds of SS-screened individuals; however, these are accumulating gradually. With further refinement of assays and validation of novel biomarkers in self-collected samples, there is a clear potential for increasing SS accuracy and PPV. The potential differentiation of self-collection protocols for vaccinated versus non-vaccinated individuals also represents an open issue. In conclusion, HPV-based self-collection techniques can effectively address limited uptake alongside other conventional cervical screening drawbacks; however, assays, logistics and infrastructures need further optimization to increase the efficacy, effectiveness and cost-effectiveness of SS approaches. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the frequency and clinicopathological characteristics of HPV-independent cervical squamous cell carcinoma (CSCC). A total of 3869 patients with CSCC from 2017 to 2021 were searched. p16INK4a immunochemistry (IHC), two HPV-DNA(L1) polymerase chain reactions and HPV mRNA in situ hybridization were performed. Viral copies were detected using the 21 HPV quantitative test. Six cases showed negative results in all four assays (group 1, 0.16%). Twenty-seven cases showed discordant results (group 2), and 3836 cases presented all-positive results (group 3). p16INK4a IHC showed similar sensitivity, specificity, and positive predictive value compared to the other three direct HPV assays. 21 HPV genotyping showed 100% of negative predictive value. HPV copies were extremely lower in Group 2 than in Group 3 (P < 0.01), but were not significantly different from those in Group 1. Older age, advanced FIGO stage (III-IV) and abnormal p53 (p53abn) IHC were independent predictors of HPV-negative status in univariate and multivariate logistic regression. Group 2 had similar proportions of age >60 years and p53abn IHC with Group 1, but had fewer cases with advanced FIGO stage (P < 0.05) and TILs (P < 0.05). Groups 1 and 2 had worse disease-free survival (DFS) and disease-specific survival (DSS) than Group 3 (P < 0.01), while no significant difference was found between these two groups. HPV-negative status was a risk factor for both DFS (P < 0.05) and DSS (P < 0.01) in univariate but not multivariate Cox regression. Joint detection of multiple technologies and evaluation of clinicopathological characteristics discriminate between HPV-independent and low-copy HPV-associated CSCC cases that present similar prognoses. Additional attention should be paid to these low-copy HPV-associated cases in clinical practice. • Joint detection of HPV-testing technologies discriminated between HPV-independent and low-copy HPV-associated CSCC cases. • p16INK4a IHC was an equally useful HPV-positive indicator compared with the other three direct HPV tests. • Older age, advanced FIGO stage (III-IV) and abnormal p53 (p53abn) IHC were the independent risk factors for HPV-negative status. • Low-copy HPV-associated cases deserved attention by showing similarly poor prognosis with the HPV-independent CSCC. [ABSTRACT FROM AUTHOR]

Background: Stillbirth is one of the most common and preventable adverse outcome of a pregnancy. This significantly contributes to the perinatal mortality and is an indicator of quality of antenatal care. Perinatal audit and classification of causation is a crucial step towards prevention of stillbirths. Numerous classification systems have been proposed and are been diversely used. The ideal system to be adapted is an important question that still remains unanswered. Objectives: The objective of the present study was to (1) Evaluate the rate, characteristics, risk factors and causes of stillbirth in a referral teaching hospital, (2) To compare maternal causes assigned by the ReCoDe and WHO classification systems for the evaluation of the stillbirths in a hospital setting. Methods: This was a retrospective descriptive study, where the details of the stillbirths born from August 2016 to July 2017 born in Maulana Azad Medical College and associated Lok Nayak Hospital were collected in prescribed predesigned format for the classification by the WHO and ReCoDe systems. The stillbirth rate and the characteristics were determined. Comparison of assigned causes, strengths and the limitations of both the classification systems were made. Results: Stillbirth rate was 37.78/1000 live births which included 45.99% and 54.01%, fresh and macerated respectively. 54.7% and 45.3% of the stillborn were male and female respectively with a mean gestational age of 34.06 weeks. The proportion of low birth weight, preterm and growth retarded babies were 79.32%, 66.67% and 23.5% respectively. Among the causes poor antenatal attendance, primiparous, prematurity, GDM, PIH, APH, birth asphyxia, poor intrapartum care was predominant. On comparing the WHO with ReCoDe system, the ReCoDe could identify only few maternal causes. Both systems matched the assignment of cause in 56.58% and failed to assign the same cause in 43.42%. The WHO system had an advantage of identifying the delays leading to causation, which can be the first vital step towards prevention of many stillbirths. Conclusion: Even though, several classification systems are available for the perinatal audit and assessment of causation of stillbirth, there is a need for a novel classification system that determines both fetal and maternal causes and the assigns due importance to preventable factors and delays.

Background: The cervical cancer is one of the leading cause of cancer death among women in developing and developed countries. Screening for cervical cancer is essential as the women are often asymptomatic and it also reduces both the incidence and mortality of the cancer cervix if detected in early stage. Objectives: We aimed to determine sensitivity and specificity of liquid based cytology (LBC) and HPV DNA to detect pre-neoplastic and neoplastic lesions of cervix. Methods: This was a prospective observational study including 506 women of reproductive, perimenopausal and postmenopausal age group who presented with abnormal vaginal discharge, post coital bleeding, abnormal uterine bleeding, postmenopausal bleeding or had unhealthy cervix on examination, who were subjected to screening by doing LBC and HPV DNA testing. The diagnosis of LBC and HPV DNA was compared against the gold standard of cervical biopsy. The data was entered in MS Excel and analysed using SPSS ver 21.0. A p

Objective This study assessed the accuracy of detecting Human Papillomavirus (HPV) DNA in urine samples compared to cervical samples and identified factors associated with HPV DNA positivity in Uzbekistan. Methods A total of 218 paired urine and cervical samples were collected from women in Uzbekistan. HPV DNA was detected using polymerase chain reaction (PCR) with genotyping. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's Kappa coefficient were calculated. Univariate and multivariate analyses were conducted to identify factors associated with HPV DNA positivity. Results The study included 32.6% (71/218) positive HPV DNA by cervical samples, which demonstrated 19.7% (43/218) HPV DNA presence by urine samples. Urine HPV testing had a sensitivity of 57.7%, specificity of 98.6%, PPV of 95.3%, NPV of 82.9%, and Kappa coefficient of 60.1. To reveal factors associated with HPV DNA positivity, we set the positive 71 cases as the main group, and 147 negative samples as the control group. The results of the multivariate analysis found the association between HPV DNA positivity and included age 31-40 years (AOR=8.2), working as medical staff (AOR=7.51), condom use (AOR=0.12), having foamy (AOR=7.26) or purulent (AOR=6.84) vaginal discharge. Conclusion Urine HPV testing showed good agreement with cervical samples, although sensitivity was lower than some previous reports. Several sociodemographic and clinical factors were associated with HPV DNA positivity. Further optimization of urine collection, storage, and testing methods may improve sensitivity. Targeted screening of high-risk groups could enhance HPV prevention strategies in Uzbekistan., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ministry of Health of Uzbekistan's Ethics Committee issued approval 7/7-m 65. The Ministry of Health of Uzbekistan's Ethics Committee approved this study on November 30, 2020, under the reference number 7/7-m 65 . Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sharipova et al.)

Background: Cervical cancer occurs 80% in developing country including Indonesia and take place in the first rank of incidence rate and third rank in mortality rate in Asian Pacific. Natural history of cervical cancer gives a potential to get accurate screening method. Cervical cancer screening m in Indonesia use VIA and Pap smear method for women in age range 30 to 50 years old. Recently, HPV DNA test has been recommended in international and national policy as primary screening method for cervical cancer. This research aims to  asses cost-effectiveness and economic implications of specific cervical cancer screening modalities., Methods: Cost-effectiveness analysis was conducted from societal perspective. Cost data was collected from four hospitals in Indonesia. Direct medical costs were derived from discussions with an expert panel and hospital billing data, aligning with current practice guidelines. Direct and indirect non-medical costs were estimated from patient interviews. Effectiveness data for the screening methods were extracted from a systematic review of existing literature. Markov model design was used for cost-effectiveness analysis. Budget impact analysis used healthcare perspective method from its billing for cervical cancer patients., Results: Cervical cancer screening costs are calculated using direct medical, non-medical, and indirect expenses. Regarding to cost-effective analysis by incremental cost-effective ratio (ICER), pap smear for every 3 and 5 years is more cost-effective than VIA. HPV DNA also has the potential to be cost-effective. The budget impact analysis investigates scenarios, with a focus on negotiation-based cost reductions for HPV DNA testing. Controlling HPV DNA tariffs at USD 8.76 proves cost-effective., Conclusion: In conclusion, pap smear is the most cost-effective modality, while HPV DNA has the potential to be cost-effective by reducing the unit cost. Despite favorable outcomes, challenges in implementation suggest a phased approach for resource equalization before full deployment.

Jialu Li,1 Xiaoli Zhang,2 Pengpeng Wang,3 Weiping Li4 1Department of Obstetrics and Gynecology, The Second School of Clinical Medicine, Southern Medical University, Hainan Hospital of PLA General Hospital, Hainan, People’s Republic of China; 2Department of Obstetrics and Gynecology, Three Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3MyGenostics Inc., Beijing, People’s Republic of China; 4Department of Obstetrics and Gynecology, Seven Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Weiping LiDepartment of Obstetrics and Gynecology, Seven Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaEmail liweiping258@sina.comAbstract: Screening and prevention in the early stage of cervical cancer could improve the 5-year survival rate of cervical cancer by up to 90%. The occurrence rate of human papillomavirus (HPV) integration has gradually increased with the development of cervical lesions. Here, we report the case of a 43-year-old woman diagnosed with chronic cervicitis based on cervical biopsy results. After medical consultation, surgery was recommended to the patient considering her 64 HPV integration sites and other biochemical and clinical test results. The pathology result of the conical biopsy obtained during operation confirmed that both her cervix and the glands had high-grade squamous intraepithelial lesion or cervical intraepithelial neoplasia III (HSIL/CIN III). The patient underwent uterectomy and bilateral salpingectomy and was discharged thereafter. The diagnosis of the patient was revised to stage Ia1 cervical cancer. The number of HPV integration sites is suggested to be an auxiliary indicator in the early screening of cervical cancer for predicting high-grade CIN and invasive cervical cancer.Keywords: HPV DNA, DNA methylation detection, cervical cancer, precancerous lesion of cervical cancer

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary. [ABSTRACT FROM AUTHOR]

Simple Summary: The definite effects of consistent condom use following cervical local excisional procedures on preventing recurrent preinvasive disease as well as in biomarkers of HPV expression have not been studied so far. We embarked on a prospective observational study enrolling over 200 individuals who received strong advice for consistent condom use after undergoing local surgical CIN treatment. We assessed in the mid and long term (six and twenty-four-month post-op intervals, respectively) rates of CIN recurrence and the expression of HPV dependent and other biomarkers (HPV DNA, HPV mRNA E6 & E7, p16) in correlation with consistency of use. A favorable effect of routine condom use in rates of CIN relapse and biomarker expression was evident at the 6-month follow up; this was more pronounced at the 2-year assessment. In conclusion, consistent condom use following cervical local excisional treatment might influence favorably rates of CIN recurrence and biomarkers of HPV expression. Background: Several factors contribute in the cervical healing process following local surgical treatment; in a previous work our group has documented a beneficial mid-term role of regular condom use immediately postoperatively in terms of CIN relapse prevention and expression of active viral biomarkers. Materials and Methods: Aiming to investigate whether the favorable contribution of consistent condom use could be extrapolated in the longer term, we conducted a prospective single center observational study including women scheduled to undergo conservative excisional treatment for CIN (LLETZ procedure). In all women a strong recommendation for consistent use for the first 6 months was given. For 204 women who underwent the procedure and completed successfully the two-year follow up a complete dataset of HPV biomarkers' results obtained six months and two years postoperatively was available. Patients were asked to complete a questionnaire to assess condom use compliance. A 90% compliance rate represented the threshold for consistent use. An LBC sample was obtained and tested for HPV genotyping, E6 & E7 mRNA by NASBA technique as well as flow cytometry, and p16 at 0 (pre-treatment), 6 and 24 months. HPV DNA and other related biomarkers status at 6 and 24 months, treatment failures at 24 months and condom use compliance rates represented study outcomes. Results: Six months post-operatively we documented a reduction in the rates of HPV DNA positivity, which was detected in only 23.2% of compliant condom users in comparison to 61.9% in the non-compliant group (p < 0.001, OR: 0.19, 95%CI: 0.1–0.36). For the HPV mRNA test, either assessed with the NASBA method or with flow cytometry, reduced positivity percentages were observed in the compliant group, in particular 1.6% vs. 8% for NASBA and 7.1% vs. 16.4% using flow cytometry, although these differences were not statistically significant (p = 0.1039 and 0.0791, respectively). Finally, reduced p16 positivity rates were documented in the compliant group. At the two year follow up, a more pronounced difference in HPV DNA positivity rates was observed, specifically only 13% positivity among the compliant women compared with 71% of the non-compliant (p < 0.0001); this illustrates a further decreasing trend compared with the 6th month in the compliant group as opposed to an increasing tendency in the non-compliant group, respectively (difference: 9.0%, 95% CI: 0% to 20.6%, p = 0.1523). At that time, 80% of the failed treatments were HPV mRNA positive compared to 10% positivity for the cases treated successfully (OR: 34, 95%CI: 6.8–173, p < 0.0001), a finding indicative that HPV mRNA E6 & E7 positivity accurately predicts treatment failure; p16 positivity was also observed at higher rates in cases with treatment failure. Conclusions: Consistent condom use following conservative excisional CIN treatment appears to significantly reduce rates of CIN recurrence and biomarkers of HPV expression. Additional HPV vaccination at the time of treatment could further enhance the positive effect of consistent condom use. [ABSTRACT FROM AUTHOR]

Abstract Background It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. Methods We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA. Results HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90. Conclusion The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.

Introduction Cervical cancer is the fourth most common cancer among women. It is related to persistent HPV infection. In order to improve diagnostic methods, a lot of research has been focused on detecting HPV DNA. A test known as a high-risk HPV test or HPV primary screening provides very encouraging results. Objective The aim of this review is to present the actual knowledge about the possibilities of cervical cancer screening methods. Particular attention is paid to the question concerning the effectiveness of detecting viral DNA as a screening programme, compared to pap smear. State of knowledge The HPV primary screening has higher sensitivity than the cervical smear test and it is able to detect lower-stage lesions, which are considered clinically irrelevant. Nonetheless, many HPV infections recede naturally. Therefore, relying only on the results of this test may expose women to unnecessary colposcopies and stress. Due to this fact, women under 30 years should not be screened with the hrHPV test. In view of its limitations, the HPV primary screening strategy is still tested worldwide as a pilot project. In Poland in 2019, a pilot project with the hrHPV test started at the National Institute of Oncology. Conclusions Detecting viral DNA has its advantages and disadvantages. Further research is still required, but the hrHPV test has a great opportunity to become one of the main screening programmes worldwide, or at least, a valuable addition to cervical smear test.

Background: It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina.Methods: We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA.Results: HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90.Conclusion: The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Various etiological factors have been described in laryngeal carcinogenesis. Tobacco and alcohol play a major role in the development of laryngeal cancers. However, recently there has been an overshadowing of association of human papillomavirus infection in laryngeal cancers. The aim of this study is to assess the prevalence of human papillomavirus (HPV) in malignant laryngeal lesions. This is a case control study. We conducted this study using tumor tissue specimens from 30 laryngeal squamous cell carcinoma patients and benign laryngeal tissue specimens from 30 cancer-free controls. The specimens from the lesion were sent to histopathological analysis as well as DNA extraction (DNeasy® Tissue kit) and polymerase chain reaction for detection of HPV. Positive samples underwent sequencing to detect the HPV serotype. Statistical analysis was performed using SPSS software. All 30 benign laryngeal lesion specimens were negative for the HPV DNA, while 4 of the 30 (7.5%) squamous cell carcinoma lesions were positive. One was HPV 16 and another one HPV 11. Two positive cases were not able to be sequenced probably due to low viral load. Our study suggests that the proportion of laryngeal squamous cell carcinomas attributable to infection by HPV seems to be low. Further prospective studies should be conducted with a larger group of patients to confirm the role of HPV in laryngeal cancers especially in treatment response and survival. [ABSTRACT FROM AUTHOR]

Dan Pan,1,* Chan-Qiong Zhang,1,* Qi-Lian Liang,2 Xiao-Cui Hong21Department of Pathology, the Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, Zhejiang, People’s Republic of China; 2Oncology Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workBackground: Cervical cancer is strongly associated with persistent human papillomavirus (HPV) infections. The ThinPrep cytologic test (TCT), HPV DNA detection, and E6/E7 mRNA testing are widely used to screen for cervical abnormalities.Purpose: This study aimed to find a suitable method for cervical cancer diagnosis (but not for cervical cancer distant metastasis), especially among women whose TCT results are atypical squamous cells of undetermined significance (ASCUS) or worse (including ASCUS).Patients and methods: A total of 301 samples from Wenzhou People’s Hospital from June 2014 to September 2017 were collected, we conducted comparative analysis of the diagnostic performance of several conventional screening methods both individually and in combination.Results: We compared the sensitivity, specificity, positive predictive value, negative predictive value, and Youden index retrospectively estimated not only by single TCT, HPV DNA detection, or E6/E7 mRNA testing but also by combination methods, such as TCT+HPV DNA, TCT+E6/E7 mRNA, or TCT+HPV DNA+E6/E7 mRNA. Screening under TCT+E6/E7mRNA was confirmed with relatively higher sensitivity of 76.1% (95% CI: 0.659–0.841), specificity of 74.6% (95% CI: 0.681–0.803), and the highest Youden index of 0.507.Conclusion: The joint screening methods showed relatively reliable specificity and sensitivity for cervical disease screening, and detection by TCT+E6/E7 mRNA has the potential to be a widely used clinical method for cervical cancer screening.Keywords: ThinPrep cytologic test, human papillomavirus DNA, E6/E7 mRNA, cervical cancer

Infection with high-risk (HR) Human Papillomavirus (HPV) is associated with the development of precancerous lesions or invasive carcinoma of the uterine cervix. Thus, the high viral load (VL) of HR-HPV DNA currently serves as a representative quantitative marker for cervical cancer. However, the clinical significance of low HPV DNA VL remains undetermined. This study aimed to evaluate the clinical association between the low HPV DNA VL and cytology/histologic diagnosis of cervical samples. We searched the electronic medical databases for the resultant analyses of HPV genotyping among patients who underwent treatment for any cervical lesion or who had undergone gynecological examinations with any positive HPV results according to the national cancer screening service between 2015 and 2016. HPV testing with genotyping and semi-quantitative VL measurement was conducted using an AnyplexTM II H28 Detection assay (H28 assay, Seegene, Seoul, Republic of Korea). The H28 assay is a multiplex semi-quantitative real-time PCR test using the tagging of oligonucleotide cleavage and extension (TOCE) technology. The VL was semi-quantified as high (3+; positive signal before 31 PCR cycles), intermediate (2+; positive between 31 and 39 PCR cycles), or low (1+; positive after 40 PCR cycles). Out of 5940 HPV VL analyses, 356 assays (5.99%) were reported as low VL (1+) of HPV DNA. Matched cytology diagnoses were mostly negative findings (n = 347, 97.5%), except for seven cases of atypical squamous cells of undetermined significance (1.9%) and two cases of atypical glandular cells (0.6%). During the follow-up periods, abnormal cytologic diagnoses were identified, including one case of high-grade squamous intraepithelial lesion (HSIL) and two low-grade squamous intraepithelial lesions (LSILs). The matched, confirmative histologic diagnosis of HSIL cytology was compatible with chronic inflammation, wherein the two LSILs had regular check-ups. None revealed clinically concerned outcomes associated with HPV-related squamous lesions. The cytology was most likely negative for malignancy when the VL of HPV DNA was low (1+). Additional strategic monitoring and management may thus be unnecessary.

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To evaluate the Turkey's nationwide HPV DNA screening program on the basis of first 4 million screened women. Women over age 30 were invited for screening via HPV DNA and conventional cytology. Single visit screen strategy was used to collect for both screening and triage (extended genotyping and conventional pap-smear). A total of 4,099,230 patients had attended to HPV DNA cancer screening. 4.39% were found to be HPV DNA positive. The most common HPV type was 16, followed by 51, 31, 52, 56 and 18 at all age intervals and geographic regions. Cytology results were reported as "normal" in (69.2%), "inadequate sampling" in (16.6%) and as "abnormal (≥ASC-US)" in the remaining. Current Turkish screening with HPV DNA (referral to colposcopy with HPV 16 or 18 or any smear abnormality ≥ASC-US) gives overall PPV of 24.3% for ≥CIN2. Only Pap-Smear triage revealed PPV of 26.4% for ≥ASC-US thresholds. Comparison of different triage methods for ≥CIN2+ according to different HPV genotype revealed a PPV of 32,6% for HPV 16; 15,3% for HPV 18. This figure was 34.4%, 19.3%, 15.3% and 14.0% for HPV 33, 31, 45 and 35; respectively. This study involves the largest series in the world summarizing a real-world experience with primary HPV DNA screening and triage with a single visit. The results show the feasibility and applicability of such screening method in developing countries with acceptable colposcopy referral rates. Among triage tests, only pap-smear seems to be effective without a need for extended genotyping. • HPV epidemiology with the largest sample size reported up to now from a primary screening population is analyzed. • Single visit strategy with concomitant primary screening plus double triage was feasible in developing countries. • The yield of extended genotyping in addition to Pap-Smear triage was not so much effective for detecting CIN2+ lesions. • With respect the WHO cervical cancer elimination program, the study reported best available real life country model. [ABSTRACT FROM AUTHOR]

Introduction: Cervical cancer is the fourth most common cancer among women. It is related to persistent HPV infection. In order to improve diagnostic methods, a lot of research has been focused on detecting HPV DNA. A test known as a highrisk HPV test or HPV primary screening provides very encouraging results. Objective: The aim of this review is to present the actual knowledge about the possibilities of cervical cancer screening methods. Particular attention is paid to the question concerning the effectiveness of detecting viral DNA as a screening programme, compared to pap smear. State of knowledge: The HPV primary screening has higher sensitivity than the cervical smear test and it is able to detect lower-stage lesions, which are considered clinically irrelevant. Nonetheless, many HPV infections recede naturally. Therefore, relying only on the results of this test may expose women to unnecessary colposcopies and stress. Due to this fact, women under 30 years should not be screened with the hrHPV test. In view of its limitations, the HPV primary screening strategy is still tested worldwide as a pilot project. In Poland in 2019, a pilot project with the hrHPV test started at the National Institute of Oncology. Conclusions: Detecting viral DNA has its advantages and disadvantages. Further research is still required, but the hrHPV test has a great opportunity to become one of the main screening programmes worldwide, or at least, a valuable addition to cervical smear test. [ABSTRACT FROM AUTHOR]

Objective: Cervical cancer (CC) is the 4th most common cause of cancer-related deaths in women all over the world. The most important etiologic cause is HPV, and this allows tumor to have high chance of curing with early diagnosis by screening programs. However, information about long-term survival data of CC is limited in our country. In our study; we wanted to reveal the survival times of our patients with CC and the factors that predict these times. Methods: Seventy-three patients with CC, followed between 2000 and 2017 were analyzed retrospectively. Associations between clinical and histopathological parameters with overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan- Meier curves and compared by the log-rank test. Univariate and multivariate analysis were used to assess their prognostic values for PFS and OS. Results: The median age of the patients was 56 years. The most common histological subtype was squamous cell carcinoma (79.5%) followed by adenocarcinoma (16.4%).According to FIGO staging system, 31 (43.8%) of the patients were diagnosed as stage 1-2 and 42 (56.2%) were as stage 3-4.The median PFS and OS are 44 months and 78 months. The 5-year survival rate is 37.5% (12%-75%). Although there was no difference in length of life between histological subtypes, both PFS and OS were longer in patients with good ECOG performance score (0-1), early FIGO stage (1-2), tumor size <4 cm, and without parametrial and lymph node involvement. Multivariate analysis showed that ECOG performance score, parametrial involvement and lymph node involvement were independent prognostic factors for PFS and OS. Conclusion: The stage at time of diagnosis of CC patients in our region is more advanced and their 5-year survival rates are below the world average, so our women need to be better informed about this subject. [ABSTRACT FROM AUTHOR]

Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women

Despite the significant scientific evolution in primary and secondary cervical cancer prevention in the battle started by George Papanicolaou in the previous century, global cervical cancer mortality rates remain disappointing. The widespread implementation of HPV-related molecular markers has paved the way to tremendous developments in cervical cancer screening, with the transition from cytological approach to the more accurate and cost-effective HPV testing modalities. However, the academic audience and different health systems have not yet adopted a universal approach in screening strategies, and even artificial intelligence modalities have been utilized from the multidisciplinary scientific armamentarium. Combination algorithms, scoring systems as well as artificial intelligent models have been so far proposed for cervical screening and management. The impact of sexual lifestyle inherently possesses a key role in the prevalence of HPV-related biomarkers. This study aimed to investigate any possible influence of sexual behavior and demographic characteristics in the expression of HPV-related biomarkers in a colposcopy population from October 2016 to June 2017, and corroborated the determining role of age at fist intercourse; the older the age, the lower the probability for DNA positivity. Multivariate analysis illustrated additionally that a number of sexual partners exceeding 4.2 was crucial, with women with ≤5 partners being approximately four times less likely to harbor a positive HPV DNA test (p < 0.0001). Similarly, a reported partner change during the last year before HPV DNA assessment contributed to 2.5 times higher odds for DNA positivity (p = 0.0006). From this perspective, the further development and validation of scoring systems quantifying lifestyle factors that could reflect cervical precancer risk seems paramount.

Background: High-risk (HR) Human Papillomavirus (HPV) has been shown to play an important role in men in various locations in Turkey. This study aims to screen the male persistent infection with the high-risk human papillomavirus (HPV) genotype status in Turkey to provide a reference basis for formulating prevention strategies for the development of genitourinary tract neoplasia., Methods: The HPV QUANT-21 Quantitative RT-PCR Kit® was used to identify and quantify low-risk HPV (HPV 6, 11, 44) and high-risk (HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82) from male individuals in Turkey., Results: Of the total 1304 samples, 473 were positive for at least one HPV genotype, with an overall frequency of 36.2%. Two-hundred fifty-four patients were positive only for one or more LR   HPV genotypes (54%), and 219 patients were positive for one or more HR HPV genotypes (46%). The LR HPV genotype frequency was 53.7%, while the HR HPV genotype frequency was 46.3%. Our technology had the positive advantage of being able to calculate concentrations for each genotype. Genotype 51 was second in frequency but had the highest average concentration of 5.38 log (copies/sample)., Conclusion: The presence and genotype of the virus before HPV vaccination are also of increasing importance. The data obtained will serve as a guide for prevention strategies, especially vaccination. Based on our findings there is a need of new estimates of the efficacy of currently available HPV vaccines and to develop a screening program to prevent and reduce the incidence of genitourinary tract neoplasias in Turkey. Further studies are planned to measure and define the high levels of infection that may lead to the development of cervical tumors. Using this technique, it may be possible to make clinical decisions about the extent of cytological alterations.

Objective: To examine the feasibility of implementing a high-risk HPV (hrHPV) DNA-based screening program for cervical cancer and the prevalence of hrHPV DNA-positive women in a community setting in rural India.Methods: A cross-sectional study was conducted at the community level in the Hunsur taluk of the Mysore district from January to August 2016. Cervical cancer screening was conducted with self-collected vaginal samples that were analyzed using the Hybrid Capture 2 (HC2) assay (Qiagen, USA).Results: The majority of participants were aged 30-39 years, with no formal schooling, from a lower caste, and lived below an annual household income of US$1499. After group health education and one-on-one counseling, a total of 473 women underwent self-sampling. Of these, 36 (7.6%) were positive for hrHPV and only 24 (66.6%) underwent follow-up diagnostic triaging. Cancer was detected in two women, who were referred to appropriate healthcare facilities for further treatment.Conclusion: Implementation of hrHPV DNA-based screening tests using self-sampling can be feasible in rural settings in India. However, substantial resources are required for providing health education and one-on-one counseling to inform asymptomatic women about the benefits of testing and, more importantly, to improve compliance with follow-up. [ABSTRACT FROM AUTHOR]

Background In the era of precision medicine and HPV-related oropharyngeal squamous cell carcinoma (OPSCC), it is relevant to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure. The UICC 8th edition uses the surrogate marker p16 to stratify for HPV association but discordance between p16 status and HPV association has been shown. The purpose of this study was to develop a prognostic model to predict the risk of local, regional, and distant metastases and non-cancer-related death for patients with OPSCC, test the prognostic relevance of adding HPV DNA and p16 status, and validate the findings in an independent external dataset. Patients and methods Consecutive patients diagnosed with OPSCC and treated with curative radiotherapy with or without cisplatin in eastern Denmark from 2000 to 2014 were included. Characteristics included age, gender, TNM stage, smoking habits, performance status, and HPV status assessed with p16 and HPV DNA. The information was used to develop a prognostic model for first site of failure with four competing events: recurrence in T-, N-, and M-site, and death with no evidence of disease. Results Overall 1243 patients were eligible for the analysis. A prognostic model with the four events was developed and externally validated in an independent dataset with a heterogeneously treated patient population from another institution. The individual prognostication from the competing risk analysis is displayed in a user friendly online tool (https://rasmussen.shinyapps.io/OPSCCmodelHPV%5fp16/). Replacing p16 status with the combined variable HPV/p16 status influenced the HR and patients with HPV−/p16+ had significantly higher HR of M-site recurrence than HPV+/p16+ with a HR = 2.56; CI [1.30; 5.02]; P  = 0.006 (P  = 0.013 in the validation cohort). Conclusion Patients with HPV−/p16+ have significantly higher risk of M-site recurrence and could potentially be relevant candidates for clinical trials testing systemic treatments in combination with conventional treatments. [ABSTRACT FROM AUTHOR]

Objectives: Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments.Methods: 1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16.Results: HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p < 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value < 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value < 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(-) p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value < 0.005). Furthermore, patients with L1(-) p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(-) p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(-) p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value < 0.005) (Table 6).Conclusion: With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) is a known causative factor in the etiology of cervical cancer.Methods: HPV DNA genotyping was performed in menstrual blood (MB) collected in napkins from patients with cervical intraepithelial neoplasia (CIN), HPV infection and sexually active apparently normal subjects. In the same patient cohort, MB TAP1 I333V and TAP1 D637G gene polymorphisms were examined.Results: The sensitivity, specificity, and positive and negative predictive values of HPV DNA in the detection of CIN or HPV infection were 83% (223 of 268), 98% (131 of 134), 99% (223 of 226), and 74% (131 of 176), respectively. Moreover, HPV DNA was found in 24% (28/118) patients who had loop electrosurgical excision procedure treatment and 0% (0/76) HPV infected or CIN1 patient with proven recovery. On the other hand, the risk of developing high-grade CIN was significantly reduced for AG and GG genotypes compared with AA genotype and for carriers with a G allele compared with those with an A allele for both polymorphisms.Conclusions: MB HPV DNA is a potential noninvasive marker for screening and monitoring of squamous intraepithelial lesion. Together with TAP1 I333V and TAP1 D637G gene polymorphisms, the combined test may be useful for stratifying high-risk patients for better follow-up strategies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The multiple visits required for an effective Pap smear screening program is difficult to replicate in many developing countries. This precludes early diagnosis and care for patients with cervical cancer and contributes to its high mortality in these countries. HPV screening has higher specificity and high negative predictive value and has the advantage that materials can be self-collected, which permits the screening of women who for various cultural and religious reasons would be reluctant to come to the clinic to expose themselves for screening. The aim of the study was to assess the degree of agreement between self sampling for HPV DNA with samples collected by a health provider. METHODS: each respondent selected from women presenting for cervical cancer screening underwent both self- and provider sampling for HPV DNA testing using Hybribio GenoArray. RESULTATS: of the 194 women screened, 12 (6.2%) and 19 (9.8%) had HPV on self sampling and provider col-lected samples respectively. The commonest HPV type seen using both techniques was HPV 58 (2.6%). Multiple HPV genotypes were seen in 1 (0.5%) and 5 cases (2.6%) of provider and self-collected samples respectively. The high risk-HPV detection rate was 7.2% when self sampled and 6.8% when sampled by the provider. There was moderate correlation between both sampling techniques (K = 0.47, 95% CI: 21.3 - 72.3%, P = 0.05). CONCLUSION: our study shows moderate correlation between both sampling techniques. Larger multicentre studies will be needed to provide results generalisable to the Nigerian population. Keywords: Pap smear, HPV screening, cervical cancer, sample collection, self-sampling, provider collected, PCR, HPV DNA, Ile-Ife Nigeria.

Abstract Preoperative discrimination of solitary cervical branchial cleft cysts from cystic lymph node metastasis often is challenging. Surgical excision of the cystic formation and consecutive histopathological examination of tissue specimens are the only means resulting in the correct diagnosis. However, in case of malignancies surgery on the lateral neck prior to the definitive treatment is considered to negatively influence the patients' outcome. The rate of cystic lymph node metastasis in patients presenting with a lateral branchial cleft cyst, localization of the primary tumour and oncological outcome were investigated. Retrospective chart review of 131 patients presenting clinically with solitary lateral cervical cysts between. A malignant tumour was detected in 12 patients (9.2%). Malignant tumours were significantly more frequent in patients older than 40 years of age (22.0%; p = 0.0001). In patients older than 40 years of age with solitary lateral cervical cysts a malignancy should be presumed. [ABSTRACT FROM AUTHOR]

Background: The detection of human papillomavirus (HPV) E6/E7 mRNA indicates a risk of further deterioration in cervical lesions. We explored the clinical value of HPV E6/E7 mRNA detection in cervical cancer screening in women positive for HPV or with abnormal thin-prep cytology test (TCT) results in the Xinjiang region of China. Methods: A total of 6,800 women were screened in our hospital for cervical cancer by both TCT and HPV DNA testing from August 2013 to June 2015. Of these, 197 had abnormal cytological or HPV test results and subsequently underwent HPV E6/E7 mRNA detection and histopathological examination, while 101 underwent an HPV DNA typing test. Using pathological results as the gold standard, we compared the accuracies of HPV E6/E7 mRNA detection or HPV DNA type testing alone, in parallel, and in series for diagnosing high-grade cervical lesions. Results: Pathological examination revealed 80 cases of chronic cervicitis, 16 cases of cervical intraepithelial neoplasia (CIN)-I, 50 cases of CIN-II-III, and 51 cases of cervical cancer. The area under the receiver operating characteristic (ROC) curve (AUC) for diagnosing high-grade cervical lesions by HPV E6/E7 mRNA detection was 74.95% (sensitivity, 85.15%; specificity, 66.67%; Youden index, 0.139; positive predictive value, 72.9%; negative predictive value, 81.0%; positive likelihood ratio, 2.555; negative likelihood ratio, 0.222; and post-test probability, 72.9%). Conclusions: HPV E6/E7 mRNA detection is superior to HPV DNA type testing for diagnosing high-grade cervical lesions. [ABSTRACT FROM AUTHOR]

HPV‐16 and −18 account for about 80% of cervical cancers. We evaluated the performance of HPV‐16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy‐confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid‐Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage. [ABSTRACT FROM AUTHOR]

Background: The antibody responses against human papillomavirus type 16 (HPV-16) and HPV-18 are well known, but many genital HPV types are oncogenic. We assessed the correlation between detection of type-specific HPV DNA and antibodies for 11 HPV types.Methods: A total of 2024 women attending the organized national cervical cancer screening program in Slovenia were tested for cervical high-risk HPV DNA (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, -59, and -68) and serum anti-HPV antibodies. Of these, 1848 women were tested with the same methods 3 years earlier.Results: Type-specific antibodies against 10 of 11 HPV types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, and -58) were associated with concomitant presence of type-specific DNA (median odds ratio [OR], 7.5; 95% confidence interval [CI], 2.2-26.1). When the concomitant presence of type-specific HPV DNA at the 3-year visit was combined with the presence of the same HPV DNA type 3 years earlier, the statistical precision was greatly improved, and antibodies against all 11 types (HPV-16, -18, -31, -33, -35, -39, -45, -52, -56, -58, and -59) were associated with the presence of DNA of the same HPV type (median OR, 7.4; 95% CI, 4.2-12.8). Sensitivity had a slight tendency to increase (from 47% to 52%) when DNA positivity at the earlier time point was included, whereas specificity was the same (88%). Seroconversion was associated with previous HPV DNA positivity. Seropositivity mostly remained stable during the observation period.Conclusions: For 11 HPV types, type-specific seropositivity was associated with the presence of DNA of the same HPV type (either concomitantly or previously). Antibodies to these HPV types mark cumulative HPV exposure. [ABSTRACT FROM AUTHOR]

Introduction: The multiple visits required for an effective Pap smear screening program is difficult to replicate in many developing countries. This precludes early diagnosis and care for patients with cervical cancer and contributes to its high mortality in these countries. HPV screening has higher specificity and high negative predictive value and has the advantage that materials can be self-collected, which permits the screening of women who for various cultural and religious reasons would be reluctant to come to the clinic to expose themselves for screening. The aim of the study was to assess the degree of agreement between self sampling for HPV DNA with samples collected by a health provider. Methods: Each respondent selected from women presenting for cervical cancer screening underwent both self- and provider sampling for HPV DNA testing using Hybribio GenoArray. Results: Of the 194 women screened, 12 (6.2%) and 19 (9.8%) had HPV on self sampling and provider collected samples respectively. The commonest HPV type seen using both techniques was HPV 58 (2.6%). Multiple HPV genotypes were seen in 1 (0.5%) and 5 cases (2.6%) of provider and self-collected samples respectively. The high risk-HPV detection rate was 7.2% when self sampled and 6.8% when sampled by the provider. There was moderate correlation between both sampling techniques (κ = 0.47, 95% CI: 21.3 - 72.3%, P < 0.05). Conclusion: Our study shows moderate correlation between both sampling techniques. Larger multicentre studies will be needed to provide results generalisable to the Nigerian population. Keywords: Pap smear, HPV screening, cervical cancer, sample collection, self-sampling, provider collected, PCR, HPV DNA, Ile-Ife Nigeria. [ABSTRACT FROM AUTHOR]

Objective Although the relationship between human papilloma virus (HPV) and cervical cancer is well established, the prognostic value of HPV status has not been determined, largely because previous studies have yielded conflicting results. This study aimed to investigate the prognostic value of pre-treatment HPV DNA for predicting tumor recurrence in cervical cancer. Methods The study included 248 eligible patients who provided cervical cell specimens for HPV genotyping before surgery or concurrent chemoradiotherapy (CCRT). Of these 248 patients, 108 were treated with radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage IB1–IIA cervical cancer, and 140 were treated with CCRT for FIGO stage IB2–IV cervical cancer. Results HPV 16 and 18 were the two most common HPV types detected, with prevalence rates of 52.4% and 12.5%, respectively. The pre-treatment HPV DNA test showed that 18.5% of cervical cancers were HPV negative. Multivariate analysis showed that HPV negativity was associated with poorer disease-free survival (DFS) than HPV-positive status (hazard ratio [HR], 3.97; 95% confidence interval [CI], 1.84–8.58; p = 0.0005), and patients with HPV 16-positive cancers had better DFS (HR, 0.41; 95% CI, 0.23–0.72; p = 0.0019). In the surgery group, only HPV 16 positivity was significantly correlated with DFS (HR, 0.34; 95% CI, 0.12–0.96; p = 0.0416). In the CCRT group, only HPV negativity was significantly correlated with DFS (HR, 3.75; 95% CI, 1.78–7.90; p = 0.0005). Conclusions Pre-treatment HPV DNA status may be a useful prognostic biomarker in cervical cancer. The presence of HPV 16 DNA was associated with better DFS, and HPV negativity was associated with worse DFS. However, larger sample sizes and more comprehensive studies are required to verify our findings. [ABSTRACT FROM AUTHOR]

The role of human papillomavirus (HPV) in Barrett's esophagus (BE) has been examined but remains unclear. The purpose of the study is to dispute the connection between HPV and BE in a prospective case-control study. Biopsies were performed above and inside the Barrett's segment for BE patients and in the distal third of the esophagus for control patients for histological interpretation and for virological analysis. Biopsies for virological analysis were placed in a virus transport medium and immediately frozen in liquid nitrogen. Virological analysis involved real-time PC Rusing the SyBr R Δ green protocol with modified SPF10 general primers. A total of 180 patients (119 control and 61 BE, respectively) were included. In BE patients, 31, 18, and 12 patients had, respectively, no dysplasia, low-grade dysplasia, and high grade dysplasia. Overall, nine were found to be HPV positive: five were control patients and four BE patients. HPV positive status was not associated with BE. No factors were associated with HPV, in particular the degree of BE dysplasia. HPV infection appears unlikely to be significant in the etiology of BE compared with control patients. (ClinicalTrials.gov, Number NCT02549053). [ABSTRACT FROM AUTHOR]

The contribution of human papillomavirus (HPV) to the development and clinical outcome of oropharyngeal cancers has been well documented. The association of HPV in laryngeal squamous cell carcinoma (LSCC) has been examined in several studies, but controversy exists regarding its role in carcinogenesis, the outcome of the patients and thus, clinical significance of HPV testing in LSCC. In this review, we give an update of known associations between HPV-positive testing and carcinogenesis in laryngeal cancer. In an early study, the HPV-DNA detection rate in LSCC was documented being 24.0% with significant regional differences. Non-HPV-16 types were more often detected in LSCC when compared to the oropharynx. Later, single institution case series revealed markedly fewer amounts (<10%) of HPV DNA in LSCC and the results suggested that high-risk HPV infections seem to be biologically irrelevant in most LSCC. The significance of p16INK4a (p16) expression as a surrogate marker towards high-risk HPV infection and the outcome in LSCC is doubtful, since only few p16-positive LSCC samples are HPV RNA positive and accordingly there was poor correlation of p16-test results towards the outcome in LSCC. Recent meta-analysis ( n = 2739) and large case series ( n = 1042) of LSCC revealed the true rate of HPV-driven LSCC being 8.6%, respectively, <5%. In the latter the rate of DNA-, DNA/RNA-, DNA/p16, and DNA/RNA/p16 positivity was 5.7, 3.1, 1.9, and 1.5%, respectively. These results indicate relevant amounts of insignificant/transient HPV infection in LSCC specimen. However, in the same study the rate of transforming HPV infections increased since 2000, and younger patients had higher amounts of HPV-driven LSCC. Serologic testing of E6/E7 antibodies additionally revealed odds ratios between 2 and 5 as a hint for a weak contribution of high-risk HPV infection and the development of LSCC. The contribution of HPV for the development of LSCC needs future investigations, to date, routine HPV testing of LSCC specimen is not warranted. [ABSTRACT FROM AUTHOR]

The present prospective study aimed to evaluate the effects of E6/E7 protein detection by western blotting on cervical cancer (CC) early screening compared with detection by Hybrid Capture 2 (HC2) test and ThinPrep cytological test (TCT) in a Chinese population. A total of 450 cases of cervical intraepithelial neoplasia (CIN) suspected samples (positive in ≥1 indicator of TCT and HC2 test) were recruited from women who were treated at the International Peace Maternity and Child Health Hospital (Shanghai, China) from March 2014 to February 2015. Each sample was analyzed by cytological test. In addition, human papillomavirus (HPV) DNA examination by Hybrid Capture Tube test and E6/E7 protein expression detection by western blotting were performed in all samples, as well as histologic diagnosis to determine the stage of CIN. The results revealed that, for the diagnosis of CIN2+, although the sensitivity of E6/E7 protein detection was lower than that of HC2 test (71.3 vs. 96.6%, respectively), the specificity was markedly improved (67.6 vs. 5.9%, respectively). Compared with that of TCT, the sensitivity of E6/E7 protein detection was much higher (36.2 vs. 71.3%, respectively), but the specificity was lower (88.2 vs. 67.6%, respectively). In the present study, HPV E6/E7 protein expression was evaluated as a potential new biomarker for CC, with satisfactory diagnostic values for HPV types 16 and 18. The relative diagnostic value may be further improved by combination of E6/E7 messenger RNA detection. [ABSTRACT FROM AUTHOR]