High-risk Human Papillomavirus DNA Research Articles

Concurrent HPV DNA testing and a visual inspection method for cervical precancer screening: A practical approach from Battor, Ghana.

Cytology-based cervical cancer screening programs have been difficult to implement and scale up in developing countries. Thus, the World Health Organization recommends a 'see and treat' approach by way of hr-HPV testing and visual inspection. We aimed to evaluate concurrent HPV DNA testing and visual inspection in a real-world low-resource setting by comparing the detection rates of concurrent visual inspection with dilute acetic acid (VIA) or mobile colposcopy and hr-HPV DNA testing to standalone hr-HPV DNA testing (using the careHPV, GeneXpert, AmpFire, or MA-6000 platforms). We further compared their rates of loss to follow-up. This retrospective, descriptive cross-sectional study included all 4482 women subjected to cervical precancer screening at our facility between June 2016 and March 2022. The rates of EVA and VIA 'positivity' were 8.6% (95% CI, 6.7-10.6) and 2.1 (95% CI, 1.6-2.5), respectively, while the hr-HPV-positivity rate was 17.9% (95% CI, 16.7-19.0). Overall, 51 women in the entire cohort tested positive on both hr-HPV DNA testing and visual inspection (1.1%; 95% CI, 0.9-1.5), whereas a large majority of the women tested negative (3588/4482, 80.1%) for both and 2.1% (95% CI, 1.7-2.6) tested hr-HPV-negative but visual inspection 'positive'. In total, 191/275 (69.5%) participants who tested hr-HPV positive on any platform, as a standalone test for screening, returned for at least one follow-up visit. In light of factors such as poor socioeconomic circumstances, additional transportation costs associated with multiple screening visits, and lack of a reliable address system in many parts of Ghana, we posit that standalone HPV DNA testing with recall of hr-HPV positives will be tedious for a national cervical cancer prevention program. Our preliminary data show that concurrent testing (hr-HPV DNA testing alongside visual inspection by way of VIA or mobile colposcopy) may be more cost-effective than recalling hr-HPV-positive women for colposcopy.

Human Papillomavirus Infection and EGFR Exon 20 Insertions in Sinonasal Inverted Papilloma and Squamous Cell Carcinoma.

This study aimed to clarify the roles of high-risk human papillomavirus (HR-HPV) infection and epidermal growth factor receptor (EGFR) exon 20 mutations in sinonasal inverted papilloma (IP) and sinonasal squamous cell carcinoma (SNSCC). Samples were collected from 20 cases with IP, 7 with IP and squamous cell carcinoma (IP-SCC), and 20 with SNSCC and examined for HPV infection and EGFR exon 20 mutations. Low- or high-risk HPV DNA was observed in 25% of IP, 57.1% of IP-SCC, and 35% of SNSCC cases. Transcriptionally active HR-HPV infections in IP-SCC and SNSCC, accompanied by p16 overexpression, were observed in 28.5% and 25% of cases, respectively. Heterozygous EGFR exon 20 amino acid insertions (ex20ins), located between amino acids 768-774, were observed in 45% of IP, 28.5% of IP-SCC, and 0% of SNSCC and chronic sinusitis cases. EGFR phosphorylation sites were located at tyrosine (Y) 845, Y1068, Y1086, and Y1197 and induced PI3K/AKT/mTOR activation. The phosphorylation pattern of EGFR with ex20ins resembled that of HPV-related SNSCC and oropharyngeal cancer. The transcriptionally active HR-HPV infection and ex20ins might be responsible for the pathogenesis of IP-SCC cases with different fashions. Since IP-SCC might be a multifactorial disease, further investigation is needed to understand IP-SCC etiology.

Meta-analysis on the Diagnostic Performance of p16/Ki-67 Dual Immunostaining for Cervical Cancer Screening

Background: This article discusses cervical cancer and its higher incidence in LMIC compared to HIC due to limited resources and poor prevention strategies. It is preventable through early detection of persistent high-risk HPV infection, which is a critical promoter. Screening methods have evolved from pap smear cytology to HPV-DNA testing and currently to co-testing, but these methods still result in false positives and high colposcopy referrals. p16/Ki-67 dual immunostaining was proposed as a biomarker for cervical cancer triage due to its ability to detect HPV-mediated neoplastic transformation. The aim of the study was to evaluate the sensitivity and specificity of this dual staining method through a review and meta-analysis of published data.Material and Methods: The search was based on PRISMA guidelines using specific MeSH terms and keywords. The search was limited to publications that compared p16/Ki-67 dual immunostaining to Pap cytology and/or high-risk HPV-DNA and included colposcopy biopsy results as the diagnostic standard. The study focused on diagnostic performance outcomes such as sensitivity, specificity, and diagnostic odds ratio. To be eligible for meta-analysis, a publication must report the diagnostic performance at predicting CIN2+. Results: A total of 24 studies were included in the review and 21,450 samples were used for dual immunostaining. The results showed that dual immunostaining was significantly more sensitive than pap cytology (75.9% compared to 71.1%) and had a higher specificity (79.7% compared to 64.3% for pap cytology and 48.9% for HPV-DNA). A meta-analysis showed that dual immunostaining had a higher pooled diagnostic odds-ratio compared to pap cytology and HPV-DNA, indicating a better test power. Conclusions: The study suggested that dual immunostaining is a better approach for detecting HPV-induced cervical cancer compared to traditional screening methods. The authors suggest that despite its reduced sensitivity, dual immunostaining should be considered as a promising alternative, especially in large-scale testing.

Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region

Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUPHNSCC), much less is known. We assessed a consecutive cohort of CUPHNSCC diagnosed from 2000-2018 for HPV DNA, mRNA, p16INK4a (p16) expression, and risk factors to identify prognostic classification markers. In 32/103 (31%) CUPHNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUPHNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. Despite obvious differences, CUPHNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUPHNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles.

The Impact of Human Papilloma Virus on Human Reproductive Health and the Effect on Male Infertility: An updated Review.

It is believed that human papilloma virus infection (HPV), which is caused by the DNA virus, is the most prominent factor contributing to sexually transmitted disease (STD) in the world, with males having a prevalence rate of 3.5-45% while that women are 2-44%. Infertility is a rising problem on a global basis, affecting anywhere from 10-30 % of couples who have reached reproductive age. This study aims to investigate the existing research on HPV, its connection to male infertility, and how it could be a helpful tool for medical professionals managing HPV in the context of reproductive health care. Infection with HPV has been identified as a risk factor for several spontaneous abortions; however, there is a lack of evidence on how HPV influences individuals undergoing assisted reproductive technology (ART) in terms of live births. The significance of the immune response to HPV-infected male reproductive system cells and its effect on embryos, as well as the oxidative stress generated by high-risk HPV DNA damage and genomic instability, is discussed in this review. Further, the association between male individuals infected with HPV and asthenozoospermia should provide a compelling case for vaccinating young people against HPV. This article is protected by copyright. All rights reserved.

Human papillomavirus testing on self-collected samples to detect high-grade cervical lesions in rural Bhutan: The REACH-Bhutan study.

"REACH-Bhutan" aimed to evaluate the feasibility and clinical performance of a community-based screening program for cervical cancer in rural Bhutan using self-collected samples for high-risk human papillomavirus (HR-HPV) testing. In April/May 2016, 2590 women aged 30-60 years were screened across rural Bhutan by providing a self-collected sample for careHPV testing. All careHPV-positive women, plus a random sample of careHPV-negative women, were recalled for colposcopy and biopsy. Self-samples also underwent GP5+/6+ polymerase chain reaction (PCR)-based HR-HPV DNA detection and genotyping. Cross-sectional screening indices were estimated against histological high-grade squamous intraepithelial lesions or worse (hHSIL+), including imputation of hHSIL+ in women without colposcopy. HR-HPV positivity was 10.2% by careHPV and 14.8% by GP5+/6+ PCR. Twenty-two cases of hHSIL+ were histologically diagnosed, including one invasive cancer; an additional 7 hHSIL+ were imputed in women without colposcopy. HR-HPV testing by GP5+/6+ showed higher sensitivity for hHSIL+ (89.7%, 95% CI 72.6-97.8) than careHPV (75.9%, 95% CI 56.5-89.7). Negative predictive value was also slightly higher for GP5+/6+ (99.9%, 95% CI 99.6-100) than careHPV (99.7%, 95% CI 99.4-99.9). Specificity, however, was lower for GP5+/6+ (86.1%, 95% CI 84.6-87.4) than careHPV (90.6%, 95% CI 89.4-91.7), as was positive predictive value (6.9%, 95% CI 4.5-9.9 vs. 8.5%, 95% CI 5.4-12.6). Of 377 HR-HPV-positive women by GP5+/6+, 173 (45.9%) were careHPV-positive, including 54.7% HPV16-positive and 30.2% HPV18-positive women. The final REACH-Bhutan results show that screening for cervical cancer with self-collection of samples and HR-HPV testing, in addition to our previous report of achieving high participation, can also perform well to detect women with hHSIL+.

HPV DNA pozitif olguların servikal smear ile korelasyon sonuçları her zaman uyumlu mudur?

Aim: Cervical cancer is a type of genital cancer which come second after breast cancer in women and may cause death. However, it can be prevented with screening tests by ensuring early diagnosis. Most of cervical cancers (99.7%) are associated with Human Papilloma Virus (HPV) and it is known that HPV must be present for the generation of cervical cancer. Thus, 70% of the patients have been found to be positive for HPV-16 and HPV-18. Both the association with cervical cancer and HPV and data related to development of cancer and dysplasia was researched retrospectively in this study. It was aimed to analyze and use the results by examine if the smear results of the patients and the HPV results are compatible in all HPV positive cases.
 Material and Method: 1050 patients who were examined by gynecologist and taken Pap smear test at the end of the examination during July 2020 and March 2022, were included in our study. In all cases the Pap test was re-evaluated by the same pathologist using the 2014 Bethesda System. High-risk HPV (HR HPV) DNA (HPV types 16,18,31,33,35,39,45,51,52,56,58,59,66,68) tests results, applied to the patients at an external center, were reviewed. Results of patients diagnosed as LSIL, HSIL and cervical cancer by Pap smear test were evaluated again beside HPV DNA analyses and their clinical information. Chi-square test was used for statistical analysis. p

Association between human papillomavirus and oral cancer: a literature review.

HPV plays a vital role in the development of cervical cancers and oropharyngeal cancers, but it is controversial whether HPV is involved in oral cancer development and to what extent. In this review, the clinical characteristics, diagnosis, treatment, and prognosis of HPV-positive oral cancers are summarized, and the mechanisms of HPV-related oral cancer development are discussed. HPV DNA positivity rates are 20-30% in oral squamous cell carcinoma (OSCC), and HPV16 is the most common high-risk HPV. E6/E7 mRNA positivity rates are 2-6% in OSCC. Detection of both high-risk HPV DNA and E6/E7 mRNA is recommended to determine the presence of active HPV, in agreement with high-risk HPV infection in OSCC. Surgical treatment is the first-line therapy for HPV-positive and -negative oral cancer, but there is no unified view about the prognosis of HPV-positive OSCC patients. HPV16 may play a vital role in malignant transformation in oral epithelial dysplasia, and a model of synergistic carcinogenic impact of HPV and tobacco smoking is predicted. Additionally, it is hypothesized that there are different HPV-associated oral cancers, such as integrated HPV DNA-positive OSCC with stable E6/E7 expression and episomal HPV DNA-positive OSCC. In summary, the role of HPV in oral carcinogenesis seems to be limited because of the low E6/E7 positivity in OSCCs; however, episomal HPV DNA may play a vital role in the malignant transformation of HPV-positive oral premalignant lesions. Further investigation is required to promote new insights into the role of episomal HPV DNA in oral carcinogenesis.

Comparison of the AmpFire and MA-6000 polymerase chain reaction platforms for high-risk human papillomavirus testing in cervical precancer screening

High-risk human papillomavirus (hr-HPV) testing for primary cervical precancer screening offers an opportunity to improve screening in low-middle income countries (LMICs). This study aimed to compare the analytic performances of the AmpFire and MA-6000 platforms for hr-HPV DNA testing in three groups of women screened for hr-HPV types in Ghana: group 1 with 33 GeneXpert-archived ThinPrep/liquid-based samples subjected to both tests, group 2 with 50 AmpFire-archived dry brush samples subjected to MA-6000 testing, and group 3 involving 143 cotton swab samples simultaneously subjected to both tests without archiving. The overall agreement rates were 73 %, 92 %, and 84 %, for groups 1–3, respectively, and 84 % (95 % CI, 78.6–88.6) for the entire group. Neither AmpFire nor MA-6000 was more likely to test hr-HPV positive in all three groups and the combined group. Group 1 showed fair agreement without statistical significance (κ = 0.224, 95 % CI, −0.118 to 0.565), while group 3 showed significant moderate agreement (κ = 0.591, 95% CI, 0.442–0.741). Group 2 showed an almost perfect significant level of agreement (κ = 0.802; 95 % CI, 0.616–0.987). Thus, both platforms showed statistically significant moderate to near-perfect agreement for detecting hr-HPV in cervicovaginal samples, with variation according to archiving conditions and duration between sample collection and retesting. For LMICs using these platforms for COVID-19 testing, as the COVID-19 pandemic subsides, the platforms can become available for running other tests such as hr-HPV DNA testing for cervical precancer screening.

Utilizing first void urine for high-risk HPV testing for cervical cancer screening in HIV-positive women in Katete, Zambia

BackgroundThe World Health Organization targets to screen 70% of women worldwide twice for cervical cancer by the year 2030, first by age of 35, and again by the age of 45. However, with the current low screening coverage in many developing countries, this may not be achieved because the invasive sampling method is unacceptable to some. In Zambia, for instance, despite the availability of free cervical cancer screening through the establishment of the Cervical Cancer Prevention Programme, some women are still reluctant to go for screening. First void urine sampling is non-invasive and thus has the potential to increase screening coverage. We aimed to determine the performance of first void urine for high-risk human papillomavirus DNA detection, the prevalence of high-risk HPV, and the acceptability of first void urine sampling.Materials and methodA comparative cross-sectional study was conducted among 100 HIV- infected women at St Francis’ Hospital in Zambia, attending the routine HIV/AIDS services and cervical cancer screening. 17 mL of first void urine sample collected by each participant was immediately mixed with 3 mL of 0.5 M EDTA preservative solution before cervical sample collection by the clinician. For testing, 2 mL of first void urine and 1 mL of the cervical sample were tested using the GeneXpert platform. An interview-based questionnaire was used to gather data on the acceptability of first void urine sampling. Data was analyzed using Stata version 17.ResultsThe mean age of the participants was 42.58 years (95% CI 40.98–44.19; SD 8.01). High-risk HPV prevalence was 34% (95% CI 24%-43.9%) in both cervical and first void urine samples. Sensitivity and specificity were 84.8% (95% CI 68.1%–94.9%) and 92.3% (83%–97.5%), respectively. There was 89.80% agreement between the samples (κ = 0.77; 95% CI 0.64–0.91). First void urine sampling was highly accepted.ConclusionHigh-risk HPV DNA can be detected in first void urine samples using the GeneXpert, with a substantial agreement with cervical samples. An affordable preservative such as Ethylenediamine tetraacetic acid can prevent DNA degradation. With optimization, first void urine sampling has the potential to increase screening coverage.

Causal Link of Human Papillomavirus in Barrett Esophagus and Adenocarcinoma: Are We There Yet?

Esophageal cancer is a relatively common malignancy worldwide with a high mortality (5-year survival of <15%). Despite screening, surveillance, improved imaging and treatment, the exponential rise in OAC continues. The strongest risk factors for OAC are chronic heartburn and metaplastic transformation of the lower third of the esophagus (Barrett's esophagus). The risk profile includes Caucasian race, male gender older age, obesity and smoking. Although the tumor risk in BO has been progressively revised downwards, the exponential rise in OAC remains unchecked. This paradox points to an unidentified missing link. Relatively recently, we provided the world's initial data for a strong association of biologically relevant hr-HPV with BD and OAC. Since then, systematic reviews and meta-analysis have documented HPV DNA prevalence rates in OAC of between 13 to 35%. In this review, we provide some evidence for a probable causal relationship between hr-HPV and OAC. This is challenging given the multifactorial etiology and long latency. Increasingly, high-risk HPV (hr-HPV) is regarded as a risk factor for OAC. This discovery will aid identification of a sub-group of high-risk progressors to esophageal cancer by surveillance and the development of effective preventive strategies including vaccination.

HPV Molecular Genotyping as a Differential Diagnosis Tool in Cervical Cancer Metastasis

Differentiating metastatic cervical cancer from another primary tumor can be difficult in patients with a history of cervical cancer and a distant lesion. The use of routine HPV molecular detection and genotyping tests could help in these cases. The objective of this study was to identify if an easy-to-use HPV molecular genotyping assay would allow differentiating between HPV tumor metastasis and a new independent primary non-HPV-induced tumor. Between 2010 and 2020, we identified patients with a primary cervical carcinoma who also had another secondary lesion. This identification included a clinical and histologic differential diagnosis of metastatic cervical cancer versus a new primary cancer or metastatic cancer from another site. We used a routine multiplex real-time PCR (rt-PCR) AnyplexTM II HPV28 (Seegene, Seoul, Republic of Korea) to detect the high-risk (HR)-HPV genome in the distant lesions in these patients. Eight cases of cervical cancer with a new secondary lesion were identified. In seven, HR-HPV DNA was detected in the biopsy of the distant lesion, which confirmed the diagnosis of cervical cancer metastasis. In the remaining case, no HPV was detected in the secondary lung biopsy, confirming the diagnosis of new primary lung cancer. Our results pave the way for HPV molecular genotyping use in cases of newly diagnosed distant lesions in patients with a history of HPV cervical neoplasia by using a routine diagnosis process to complete the clinical and histologic differential diagnosis when confronted with ambiguous situations.

Comparison of Self- to Provider-Collected Cervical Screening with HPV DNA Test at Roi Et Province, Thailand during COVID-19 Pandemic

Objective: The authors evaluated the concordance of positivity of self- and provider-sampling collection for high-risk human papillomavirus (hrHPV) DNA assay. Acceptance towards self-collection was also explored. Materials and Methods: Five hundred thirty-five paired self- and provider-sampling cervical specimens were obtained from 30 to 59-year-old women enrolled at the gynecologic clinic at Phanomphrai Hospital, Roi Et Province, Thailand. Women performed self- and then received providersampling collection by trained nurse. Each sample was tested by COBAS® 4800 assay. Concordance in hrHPV detection between sample types was determined using Kappa (k) statistics. Sensitivity and specificity of hrHPV detection by self-collection were calculated. A hundred women were randomly invited to answer satisfaction survey afterward. Results: Twenty-seven or 5.0% of the women were positive for hrHPV DNA, which 5, 4, and 18 were HPV-16, 18, and other pooled hrHPV genotypes, respectively. Self-collection showed good concordance to provider-collection (k=0.89; p&lt;0.001). Self-collection of hrHPV detection had sensitivity of 81.5% (95% CI 61.9 to 93.7) and specificity of 100% (95% CI 99.3 to 100). Ninety-five percent of randomly selected 100 women were satisfied with self-collection. Conclusion: Self-collected cervical sampling was comparable to provider-collected HPV DNA testing and was well-accepted. The present modality may help accelerate achieving the goal of elimination of cervical cancer campaign during the recovery phase of covid-19 pandemic. Keywords: Cervical screening; HPV DNA Test; Self-collection; Covid-19

Study to Determine Concordance between High-Risk Human Papilloma Virus DNA Detection in Self Collected First Voided Urine Samples and Health-Care Worker Collected Cervical Samples in a Subset of Women with Proven Histopathological Precancerous and Cancerous Lesions of the Cervix.

The objective of our study was to assess whether urinary samples for human papilloma virus (HPV) detection are a good predictive marker of cervical cancerous and precancerous lesions, by comparing against results from cervical scrapings as the gold standard test. The study is a hospital-based cross-sectional study wherein symptomatic women were screened at the colposcopy clinic. Paired samples-cervical scrapings/washings and urine samples were tested for hr-HPV for women who were found to harbor premalignant and malignant lesions of the cervix in histopathological lesions, by multiplex real-time polymerase chain reaction and HPV genotyping. Diagnostic accuracy was tested by calculating concordance with Cohen's kappa with hr-HPV detection in cervical samples as the gold standard. A total of 295 patients undergoing colposcopy were recruited in the study, out of which 54 had histopathological-proven premalignant and malignant lesions of the cervix. Overall, positivity rate in urinary samples for both HPV 16 and 18 combined is 64.81%, whereas for cervical samples is 68.51%. HPV 16 was seen in 30 (55.5%) and 32 (59.3%) cervical and urinary samples, respectively, whereas HPV 18 was seen in 7 (12.9%) and 6 (11.1%) samples, respectively. There was substantial concordance between the cervical samples and first-void urinary samples results with Cohen's k: 0.6988 (95% confidence interval: From 0.507 to 0.891). There was 85.96% agreement among all the tests that were performed with only 14.04% disagreement. The study showed that HPV DNA detection from the urine and cervical samples showed significant agreeability for the detection of precancerous and cancerous lesions of the cervix among women with abnormal histology results. Thus, urinary sampling can be done as a potential replacement for cervical sampling methods with the added benefit as it can be used in females reluctant to provide cervical samples, if there is no availability of skilled workforce for collecting samples, for mass screening, and for the follow-up of vaccination programs.

Prevalence of HPV infection and cervical intraepithelial lesions in HIV positive and negative women in the city of Florianopolis

Introduction: The human papillomavirus (HPV) is the most common sexually transmitted infection among women. The HPV of high oncogenic risk, associated with other factors, presents a risk of progressing to a precancerous lesion of the uterus and even cancer. Such an evolution is related to the persistence of the infection and other factors, mainly those that interfere with women’s immunity. The immunosuppression caused by HIV infection is an important factor for viral persistence and the onset of these lesions. Objectives: To compare the prevalence of HPV infection and cervical intraepithelial lesions in HIV-positive and negative women and describe the possible associated risk factors. Methods: The sample consisted of 50 HIV positive women (study group) and 50 HIV negative women (control group) recruited from the public health system of Florianópolis from January to April 2022. Cervical samples were collected for cytological analysis and for the detection of high-risk oncogenic HPV DNA by polymerase chain reaction (PCR). Categorical variables were compared using the chi-square test, with a significance level set at 5% Results: HPV infection was more prevalent in the control group; however, HIV positive women presented higher frequency of intraepithelial lesions diagnosed on cytology. Factors such as higher number of sexual partners, depression and smoking were more frequent in the group of HIV positive women. CD4 T cells lower than 200 cells/mm3 was associated with a higher number of altered Pap smears and a positive HPV DNA test. The use of combination antiretroviral therapy and undetectable viral load were associated with more frequent normal cytology and undetected HPV DNA. Conclusion: The prevalence of cervical intraepithelial lesions in HIV-infected women is higher than among women without the infection. The presence of HIV infection was the most important risk factor associated with the development of cervical lesions.

Oral Human Papillomavirus Infection among Smokeless Tobacco-using Tribal Women in Mysuru, India.

Smokeless tobacco (SLT) is consumed by more than 300 million people worldwide. Studies show high use among Indian indigenous women who are also at high risk for oral cancers. Both human papillomavirus infection (HPV) and SLT have been associated with oral cancer, this study examined the presence of high-risk HPV in oral samples collected from tribal smokeless tobacco users in Mysuru, India. Between June and August 2019, 100 tribal females (50 SLT-users and 50 non-users) from rural Mysuru District, Karnataka, were enrolled in a cross-sectional study. Following informed consent, demographic data and oral samples were collected and processed using a digene HC2 High-Risk HPV DNA test (Qiagen, USA). On average participants were 45.5 (SD: ±6.6) years. Chronic SLT users were mostly married (73%), Hindu (100%), illiterate (62%), and employed (90%). One woman was positive for high-risk HPV infection. Oral HPV infection was low in this sample and this is consistent with the literature from other low and middle-income countries. SLT use is high in this group so interventions to reduce tobacco use are warranted.

A low-cost, paper-based hybrid capture assay to detect high-risk HPV DNA for cervical cancer screening in low-resource settings.

Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of <$3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ("Xpert"), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.

Evaluation of the clinical performance of OncoPredict HPV® SCR assay within the VALGENT-2 framework.

Human papillomavirus (HPV) assays used in cervical cancer screening should be clinically validated according to international criteria. OncoPredict HPV® Screening (SCR) is a partial genotyping multiplex real-time PCR assay targeting E6/E7 genes of 13 high-risk (hr) HPVs. OncoPredict HPV® SCR (index assay) identifies HPV-16 and HPV-18 separately, 11 other hrHPV in aggregate and includes quality controls for sample adequacy, DNA extraction efficiency and PCR inhibition. 1300 VALGENT-2 study samples (from women aged 20-60 attending the Scottish cervical cancer screening program) were tested with the index assay and the GP5+/6+ PCR enzyme immunoassay (standard comparator assay). Non-inferior accuracy detecting cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) of the index versus comparator was verified. Intra- and interlaboratory reproducibility of the index was evaluated by overall concordance and Cohen's kappa, using a sub-population (n = 526). Relative sensitivity and specificity for CIN2+of the index versus comparator were 1.01 (95% confidence interval [CI]: 0.99-1.03) and 1.02 (95%CI: 1.0-1.04), respectively. Noninferiority pvalues were all ≤0.05, except for CIN3+in patients ≥30 years. Excellent intra- and interlaboratory reproducibility was shown with concordance >98% and kappas >0.95. OncoPredict HPV® SCR fulfills the three international validation criteria for hrHPV DNA tests in cervical cancer screening.

Cobas® 4800 HPV test is accurate for detecting high risk Human Papillomavirus from urine samples at dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia

HIGHLIGHTS 1. The presence of Human Papillomavirus (HPV) can be detected using urine samples, as compared to cervical samples, by means of Cobas® 4800 HPV test.2. The concordance between cervical and urine samples for HPV DNA was found as much as 84.72%.3. Urine samples subjected to Cobas® 4800 HPV test is helpful to treat HPV infection. ABSTRACT Objective: To find the accuracy, sensitivity, specificity, as well as predicted values, both positive and negative, of urine samples using Cobas® 4800 in detecting high risk Human Papillomavirus. Materials and Methods: This study was a cross-sectional study with a total of 72 samples taken from medical records of hrHPV DNA examination with Cobas® 4800 in 2017-2020. Study subjects were called for re-examination of urine samples and cervical samples using Cobas® 4800. Samples with positive hrHPV DNA in the cervix, urine, or both were examined for cervical fluid-based cytology (LBC). Data were analyzed using Chi-square. Results: Overall, 84.72% agreement was detected through specimens of urine and cervical mucus tested of hrHPV DNA with Cobas® 4800. In all samples, a significant rate of concordance detection of hrHPV DNA with Cobas® 4800 was reported (ka = 0.62; 95% IC: 39-84). In this population, in determining the presence of hrHPV DNA in cervical and urine specimens, it was found that the sensitivity, specificity, positive predictive value and negative predictive value were respectively 87.5% (95% IC: 64–97%), 84% (95% IC: 72–91%), 60.9% (95% IC: 40.8–77.8%), and 96 % (95% IC: 86.3–98.9%). Conclusion: The presence of hrHPV infection in the cervix can be determined by detecting hrHPV DNA in the urine. According to these findings, urine samples subjected to the Cobas® 4800 HPV test may be helpful for the clinical treatment of HPV infection.

High-risk HPV testing vs liquid-based cytology for cervical cancer screening among 25- to 30-year-old women: A historical cohort study.

High-risk human papilloma virus (hrHPV) DNA testing is more sensitive than cytology screening, achieving greater protection against cervical cancer. Controversy exists regarding the preferred screening method for women 25-30 years of age. At this age, infection with HPV is common and usually transient. Consequently, hrHPV screening in this age group is fraught with high false-positive screening results, leading to more colposcopies and unnecessary treatments with the potential for harm. In the present study, we aimed to compare the results of two screening methods in relation to high-grade cervical intraepithelial lesion detection rate in the young age group of 25-30 years. Retrospective information on cervical cytology, hrHPV testing, colposcopy referrals and histologic results, from one screening round, were retrieved from the Maccabi HealthCare Health Maintenance Organization centralized database during the study period from March 1, 2017 to April 1, 2019 for 25- to 30-year-old women. Screening with hrHPV testing for types 16, 18 and 12 other hrHPV types was compared with the conventional PAP liquid-based cytology (LBC) test. Odds ratio (OR) of detection with 95% confidence interval (CI) was calculated for cervical intraepithelial neoplasia (CIN) grade 3 or higher (CIN 3+). During the study period, 42 244 women 25-30 years old underwent cervical cancer screening; of them, 20 997 were screened with LBC between March 1, 2017 and March 1, 2018 and compared with 21 247 who were screened with hrHPV between April 1, 2018 and April 1, 2019. Testing for hrHPV resulted in a higher colposcopy referral rate compared with primary LBC screening: 9.8% vs 7.8%, respectively; (OR 1.28; 95% CI 1.2-1.37; p< 0.001). Screening with hrHPV led to significantly higher detection of CIN 3+ lesions (OR 1.4; 95% CI 1.2-1.6; p< 0.001) compared with LBC. HPV infections with non-16/18 hrHPV (other hrHPV) were the most prevalent (84.8%). In women 25-30 years old, primary hrHPV screening was associated with a higher detection rate of CIN 3+ compared with cytology screening and should be considered for primary screening in this age group.