High-risk Human Papillomavirus DNA Research Articles

Genetic characteristics of human papillomavirus type 16, 18, 52 and 58 in southern China

Persistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 338 viral genomes of four major HPV types, including HPV 16 (n = 82), 18 (n = 35), 52 (n = 121) and 58 (n = 100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 sublineages associated with potentially high oncogenicity. These findings expanded our knowledge of the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.

Prevalence of high-risk human papillomavirus DNA and mRNA and its association with abnormal anal cytology in the Czech male anal cancer screening cohort.

Anal cancer (AC) screening is justified in high-risk populations, particularly HIV-positive men having sex with men (MSM). HR-HPV testing could improve the efficiency of cytologically based screening of AC, as in the screening of biologically analogical cervical cancer. The specificity of HR-HPV testing is influenced by the prevalence of HR-HPV infection in the screened population. Reported anal HR-HPV DNA prevalence in MSM is high, but HR-HPV mRNA reflects rather long-term infections and is more specific for high-grade lesions. However, no data were published about HR-HPV DNA and mRNA prevalence in the Czech AC screening population. Results of liquid-based anal cytology of 203 predominantly HIV-positive MSM from the Czech AC screening cohort were correlated with results of DNA and E6/E7 mRNA testing of 14 HR-HPV types, and HPV16 genotyping. Eighty-one MSM underwent a standard anoscopy. A total of 109 (53.7%) samples had abnormal cytology, with 12 (5.9%) ASC-H/HSIL, 67 (33.0%) samples cytologically negative, and 27 (13.3%) unsatisfactory. HR-HPV DNA was detected in 134 (66.0%) and HR-HPV RNA in 72 (35.5%) anal smears. HR-HPV mRNA and HPV16 mRNA positivity were associated with abnormal cytology (p= .0037, p= .0021). No significant association was found between HR-HPV DNA or HPV16 DNA positivity and abnormal cytology. No high-grade lesions were revealed by anoscopy. Prevalence of anal HR-HPV DNA among Czech MSM is high, however, the prevalence of HR-HPV mRNA is half and associated with abnormal cytology. Our results indicate an increased efficiency of cytological screening when combined with HR-HPV mRNA testing.

Genotyping of human papillomavirus DNA in Wielkopolska region.

Human papillomavirus infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV leads to development of high-grade squamous intraepithelial lesions that can eventually transform into cervical cancer. The aim of the study was to assess the HPV genotype distribution in patients with abnormal pap smear and provide prospective study. We obtained material from 674 women who registered to Specialist Medical Practice in the years 2008-2020. The sample for the molecular test was collected using combi brush and forwarded to the independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and reverse hybridization line probe assay for virus genotyping. Sequence analysis was performed to characterize virus genotypes in HPV - positive samples. We found that 53% of patients tested positive for HPV. The percentage decreased with age. The following HPV types were the most common: HPV - 16 (24.5%), HPV - 53 (13.1%), HPV - 31 (10.3%), HPV - 51 (9.7%), HPV - 56 (9.5%). To our knowledge, this study is the largest assessment of HPV genotypes in Poland. Our results suggest that type-specific, high-risk HPV DNA - based screening should focus on HPV types 16, 31, 51, 56.

Prognostic value of high-risk human papillomavirus DNA and p16INK4a immunohistochemistry in patients with anal cancer: An individual patient data meta-analysis

BackgroundHigh-risk human papillomavirus (hrHPV) types represent the aetiological agents in a major proportion of anal squamous cell carcinomas (ASCC). Several studies have suggested a prognostic relevance of HPV-related markers, particularly hrHPV DNA and p16INK4a (p16) protein expression, in patients with ASCC. However, broader evaluation of these prognostic marker candidates has been hampered by small cohort sizes and heterogeneous survival data among the individual studies. We conducted an individual patient data (IPD) meta-analysis to determine the prognostic value of hrHPV DNA and p16 in patients with ASCC while controlling for major clinical and tumour covariates. Patients and methodsA systematic literature search was conducted to identify all published studies analysing p16 alone or in combination with hrHPV DNA and reporting survival data in patients with ASCC. Clinical and tumour-related IPD were requested from authors of potentially eligible studies. Survival analyses were performed with a proportional hazard Cox model stratified by study and adjusted for relevant covariates. The study-specific hazard ratios (HRs) for the exposures were pooled using a random-effects model. Kaplan-Meier curves from different studies were pooled per exposure group and weighted by the study's total sample size. ResultsSeven studies providing IPD from 693 patients with ASCC could be included in the meta-analysis. Seventy-six percent of patients were p16+/hrHPV DNA+, whereas 11% were negative for both markers. A discordant marker status was observed in 13% of cases. Patients with p16+/hrHPV DNA+ ASCC showed significantly superior overall survival (OS) compared with patients with p16-/hrHPV DNA- tumours (pooled adjusted HR = 0.26 [95% confidence interval {CI}, 0.14–0.50]) with pooled three-year OS rates of 86% (95% CI, 82–90%) versus 39% (95% CI, 24–54%). Patients with discordant p16 and hrHPV DNA status showed intermediate three-year OS rates (75% [95% CI, 56–86%] for p16+/hrHPV DNA- and 55% [95% CI, 35–71%] for p16-/hrHPV DNA+ ASCC). ConclusionThis first IPD meta-analysis controlling for confounding variables shows that patients with p16+/hrHPV DNA+ ASCC have a significantly better survival than patients with p16-/hrHPV DNA- tumours.

The Genotype Distribution of Human Papillomavirus among HIV-Infected Women Planning Pregnancy in Irkutsk, Russia

The purpose of our research was to determine the detection frequency of 12 high-risk types of human papillomavirus (HPV) in women with human immunodeficiency virus (HIV) who are planning pregnancy and to assess the results of colposcopy and the state of the cervix in these women, depending on the presence of HPV. Methods and Results: We examined 31 women with HIV infection who sought pregnancy-planning advice at Scientific Center for Family Health and Human Reproduction Problems in Irkutsk during 2014-2015. All HIV-infected women were tested for the presence of high-risk HPV DNA in the epithelium of the cervical canal by PCR. Material for cytological examination (PAP test) was collected during gynecological examination. PAP tests were assessed according to the Bethesda system. All changes were divided into two types: ASCUS and SIL, the last was in its turn divided into two categories: LSIL and HSIL. The frequency of HPV detection in HIV-infected women planning pregnancy was 71%. HPV 16 was found in 16(51.6%) HIV-infected women and ranked first in frequency among 12 types of HPV. HPV 33 and HPV 35 were found in 15(48.4%) and 12(38.7%) HIV-infected women, respectively, and ranked the second and third in frequency among 12 HPV types. We compared abnormal colposcopy results in two groups of patients with HIV infection: Group 1 (n=22) included women with HPV and Group 2 (n=9) included women without HPV. ASCUS was detected in all patients of Group 1 (100%) and in 6(66.7%) women of Group 2. Two women (9.1%) from Group 1 were diagnosed with LSIL and 10(45.5%) women with HSIL. Conclusion: HIV-infected women planning pregnancy and living in Irkutsk form a group at high-risk of HPV infection.

Preliminary study of the use of E6/E7mRNA detection in screening and triage management of HR-HPV infection during pregnancy.

BackgroundDetection of E6 and E7 mRNA load of high-risk human papillomavirus (HR-HPV) infection during pregnancy was compared with conventional cytopathology and DNA detection by pathological examination as colposcopy to evaluate the application of E6 and E7 mRNA detection in the diagnosis and management in HR-HPV infection for high -grade cervical lesions during pregnancy.MethodsFrom January 2014 to June 2019, 1,058 pregnant women of childbearing age who were filed for regular obstetrics in the Department of Obstetrics and Gynecology, Xuanwu Hospital of Capital Medical University, were separately assessed using cervical liquid-based cytology and HPV DNA detection. If the results were abnormal, colposcopy was performed as a follow-up. The presence of HR-HPV E6/E7 mRNA fragments was detected through the HR-HPV E6/E7 mRNA test, and monitored at the same time as colposcopy. The diagnostic efficacy of the HR-HPV DNA test versus the HR-HPV E6/E7 mRNA test for high-grade cervical lesions during pregnancy was compared.ResultsThe positive rate of HR-HPV E6/E7 mRNA detection in the overall cervical intraepithelial neoplasia (CIN) and above during pregnancy was lower than that with HR-HPV DNA detection, and there was a significant statistical difference between the two methods. In CIN I and normal or inflammatory results, the positive rate of HR-HPV E6/E7 mRNA detection was lower than that of HR-HPV DNA detection, while in the results of CIN II and CIN III, the positive rate of the two was not significantly different. HR-HPV E6/E7 mRNA detection is the same as HR-HPV DNA detection, both of which increased with the severity of cervical lesions, and the positive rate increased. In cases of maintenance or progression of cervical lesions, the positive rate of HR-HPV E6/E7 mRNA detection during pregnancy can reach 81.8%. High-grade cervical lesions during pregnancy had a higher rate of reversal to a lower level after delivery.ConclusionsThe results suggested that the use of HR-HPV E6/E7 mRNA detection in cases of positive HR-HPV DNA detection can significantly improve the diagnostic specificity of CIN II and above high-grade cervical lesions.

Comparison of Cepheid Xpert HPV test and Hybrid capture 2 high risk HPV DNA test for detection of high risk HPV

Comparison of Cepheid Xpert HPV test and Hybrid capture 2 high risk HPV DNA test for detection of high risk HPV

Servikal kanser taramasında saptanan önemi belirlenemeyen atipik skuamoz hücrelerin klinik değerlendirmesi: Eskişehir deneyimi

Purpose : Aim of our study is to compare the colposcopic findings with the histopathologic results of atypical squamous cells of undetermined significance (ASCUS) diagnosed during cervical cytological screening in patients applied with various complaints and evaluated with co-test so as to to determine the clinical value of it. Materials and Methods: In this retrospective analysis 177 patients who attended between January 2011 and may 2020, aged between 24-74 years, with the result of ASCUS in their Pap smear tests, were enrolled. Colposcopic findings of cases were classified according to Reid Colposcopic Index (RCI) and compared with the histopathologic results. Results: 177 patients were analyzed and the mean age of them was 37,1±1,41 (24-74), parity 2,8±1.07 (0-11) and mean smoking was found to be 6 cigarettes/day (0-40 cigarettes/day). 148 (%83,6) of cases were in premenapouse, 29 (%16,3) of them were in postmenapousal period. 68 (%38,4) patients were diagnosed as chronic cervicitis by colposcopy assisted cervical biyopsy, rest 108 (%61,0) were determined as cervical intraepithelial lesions (CIN) [85 (%48) CIN 1, 16 (%9) CIN 2, 7 (%3,9) CIN 3] and 1(%0,5) patient was found to be cervical carcinoma (CX CA). Comparison between HPV DNA types and RCI with biopsy results was analyzed with Pearson Exact Chi-square test and found to be statistically significant between groups (p<0.001). Conclusion: Our results put forth that colposcopic evaluation is needed in patients with cytologic ASCUS results even if HR-HPV DNA test is negative. That's why Pap smear test cannot be replaced by screening only with HR-HPV DNA, co-test requirement showed to be more suitable because of cytologic evaluation involvement.

Usefulness of high-risk human papillomavirus mRNA silver in situ hybridization diagnostic assay in oropharyngeal squamous cell carcinomas

AimsThe transcriptional activity of high-risk human papillomaviruses (HR-HPV) within oropharyngeal squamous cell carcinomas (OPSCC) has been linked to improved survival of patients. HR-HPV mRNA silver in situ hybridization (SISH) was evaluated on a cohort of OPSCC and compared with viral HPV DNA tests and p16 expression. Clinical outcomes of HPV-driven OPSCC and non-HPV related OPSCC were also studied. MethodsWe evaluated 67 OPSCC and 3 papillomas, obtained from 62 patients, for detection of HR-HPV DNA by PCR tests. The positive samples were additionally studied by the SISH method using three probes of HPV16, HPV18, and HP33, and for p16 expression detected by immunohistochemistry. SISH assays were evaluated for the presence/number and intensity of signals in cancer cells. Prognostic significance of HPV status in our cohort was evaluated with univariate and multivariate statistics. ResultsAccording to the HR-HPV PCR tests, 46 (69%) OPSCC cases were HPV positive, while three papillomas were negative. Of total 46 HPV-positive OPSCCs, 43 cases were also SISH-positive, while p16 overexpression was found in 45 of 46 HPV positive OPSCC cases. In OPSCC specimens, the sensitivity and specificity of the combined SISH probes (HPV16 and 33) were both 100.00%, when compared to HPV PCR. HPV positivity of the tumors appeared significant for predicting progression-free survival, cause specific survival and overall survival in a multivariate setting. ConclusionsThe recently developed mRNA SISH methodology can detect HPV-driven OPSCCs without any additional test in 79% of cases. Positive SISH signals enable the visualization of viral transcripts required to recognize clinically relevant HPV infection. However, rare and tiny signals require an experienced pathologist to establish a consensus interpretation of results. The currently applied HR-HPV mRNA SISH analysis may serve as a groundwork for additional studies.

Salivary High-Risk Human Papillomavirus (HPV) DNA as a Biomarker for HPV-Driven Head and Neck Cancers

High-risk human papillomavirus (HR-HPV) infection is a major risk factor of head and neck cancers (HNCs). Despite the rising prevalence of HPV-driven HNC (HPV-HNC), biomarkers for detection, prognostication, and disease monitoring are lacking. To evaluate the capacity of salivary HR-HPV DNA as a biomarker of HPV-HNC, the salivary HR-HPV statuses of 491 and 10 patients with primary and recurrent HNC, respectively, were determined at diagnosis, using quantitative real-time PCR and MassARRAY. Tumor cyclin-dependent kinase inhibitor 2A (p16) expression was determined by IHC analysis. Patients with oropharyngeal cancer (OPC) (n=215) were followed up for ≤5 years. Survival characteristics were evaluated in terms of event-free and cause-specific survival. Of the primary-HNC cohort, 43.2% were positive for salivary HR-HPV DNA, with most having OPC. Salivary HR-HPV DNA was detected in 81.4% of tumor p16-positive OPC patients at diagnosis. Prognosis in salivary HR-HPV-positive OPC patients was favorable compared with that in salivary HR-HPV-negative patients (event-free survival, hazard ratio = 0.42 [95% CI, 0.21-0.81, P=0.010]; cause-specific survival, hazard ratio = 0.39 [95% CI, 0.18-0.86, P=0.019]). In therecurrent-HNC cohort, salivary HR-HPV DNA was detected in 83.3% of those who previously had tumor p16-positive HNC. These findings indicate that this liquid biopsy-based, noninvasive biomarker can play an essential role in the detection and management of HPV-HNC.

Evaluation of HPV-Related Biomarkers in Anal Cytological Samples from HIV-Uninfected and HIV-Infected MSM.

Men who have sex with men (MSM) harbor the highest risk for anal carcinoma, mainly caused by Human Papillomavirus (HPV). The use of HPV-related biomarkers in the screening for this neoplasia is still debated. We assessed the association between high-risk (hr)HPV DNA, HPV16/18 DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 with cytological abnormalities (any grade) and high-grade intraepithelial lesions (HSIL) in HIV-uninfected and HIV-infected MSM. Overall, 150 cytological samples in PreservCyt (Hologic), with a negative to HSIL report, were analyzed for hrHPV DNA, hrHPV E6/E7 mRNA, and p16/Ki-67 using the Linear Array (Roche), Aptima (Hologic), and CINtec® PLUS (Roche) assays. In HIV-infected MSM, positivity for all the biomarkers significantly increased with the cytological grade. In both populations, the association of hrHPV E6/E7 mRNA and p16/Ki-67 positivity with HPV16 did not differ significantly compared to hrHPVs other than HPV16. In HIV-uninfected MSM, the odds of having an HSIL increased approximately six times for the p16/Ki-67 positive cases. In HIV-infected individuals, all the biomarkers showed a significant association with HSIL, except for hrHPV DNA, with the strongest association observed for p16/Ki-67. The odds of HSIL increased almost 21 times in those positive for this biomarker. Our results encourage further investigation on the use of p16/Ki-67 dual staining in anal cancer screening for HIV-uninfected and HIV-infected MSM.

The Integration Pattern of Human Papillomavirus in the Host Genome as a Promising Guide for Precise Radiation Therapy in Cervical Cancer

Context: Cervical cancer (CC) is one of the most common cancers among women worldwide. Infection with high-risk human papillomavirus (HPV) is the leading risk factor for this cancer. Currently, concurrent chemotherapy and radiotherapy are the standard of care for patients with locally advanced CC. However, the response to radiotherapy varies widely among patients, underscoring the need to identify biomarkers to predict patients’ treatment outcomes. Evidence Acquisition: In order to find relevant articles, we performed a systematic search using ISI Web of Science, Scopus, PubMed, and Embase, with a combination of the keywords “human papillomaviruses”, “cervical cancer”, “radiotherapy”, “biomarkers”, “viral integration”, and “episome”. All types of studies, including observational or retrospective studies, clinical trials, congress abstracts, and case reports or case series, were examined to find relevant data. No time limitation was considered for the studies. Results: The integration of HPV DNA into the host genome is considered to be a critical step in HPV carcinogenesis. The HPV integration pattern has been investigated as a potent prognostic factor for the tailored treatment of CC. Conclusions: It is indicated that the integration state of the HPV genome in host DNA is a potential prognostic or predictive biomarker for CC response to radiotherapy.

Persistence and clearance patterns of cervical high risk human papillomavirus (Hr-HPV) infections in women with negative cytology results in Harare, Zimbabwe

Background: Persistent Hr-HPV infection is a prerequisite for cervical carcinogenesis. Knowledge of the persistence or clearance patterns of specific Hr-HPV genotypes can help clinicians to formulate interventions to prevent the development of cervical cancer. Objectives: To determine the persistence and clearance patterns of Hr-HPV infections in Zimbabwean women and to compare the persistence or clearance rates of different Hr-HPV genotypes.Design: Cross sectional descriptive study. Setting: Cimas Medical Laboratories and KAVI molecular laboratory. Subjects: Women with Hr-HPV infections and NILM cytology results on baseline assessment. Materials and Methods: The women were followed up for 24 months and retested for the presence of Hr-HPV DNA. Hr-HPV testing was done using the HPV Genotypes 14 Real-TM Quant test kit. The Hr-HPV persistence rates in women <30 years and those ≥30 years old was compared using an independent t-test. A p-value <0.05 was regarded as statistically significant. Results: A total of 52 women met the study inclusion criteria. The mean (SD) age of the study participants was 33.5 (5.5) years. Persistence and clearance rates were 34.6% [18/52] and 65.4% [34/52] respectively. The Hr-HPV clearance rates of women <30 years and those ≥ 30 years old were comparable (53% [18/34] vs. 47% [16/34], respectively; p=0.642). HPV 16 and 52 were the most persistent genotypes: 53.8% and 37.5% respectively. HPV 35 and 51 had the highest clearance rates of 100%. Conclusion: HPV 16 and HPV 52 were the most persistent Hr-HPV genotypes; and HPV 35 and HPV 51 had the highest clearance rates in Zimbabwean women.

Viral and cellular biomarkers used for improving prevention and management of cervical cancer

Cervical cancer remains one of the preventable cause of women’s death, the second most common cause of death in Europe. Several screening tests for precancerous lesions are available, including cervicovaginal cytology and screening of high-risk human papillomavirus (HPV) strains – 16, 18, 31, 33. Cervical cytology (Babeş-Papanicolau smear test) remains the elected method for cervical cancer screening in many countries. Last decades, HPV DNA sequence was identified, including gene number and encoded proteins. HPV DNA gene expression involves the use of multiple promoters and complex patterns of splicing, which served as a model for the elaboration of cellular and molecular biomarkers for the identification. Herein, we present the usefulness and efficiency of viral and cellular biomarkers in improving the diagnosis and managing precursor lesions of cervical cancer. Viral and cellular biomarkers can help differentiating low-grade lesion leading to a better diagnosis. HPV DNA tests, although a primary screening method in actual guidelines, can serve as a better screening test method. Other viral biomarkers that include E6 and E7 mRNA testing and determining the methylation of viral genes have good test screening results. Cellular biomarkers such as the immunocytochemical staining of p16INK4a, alone or combined with the proliferation marker Ki-67, can reveal anomalies in the cell cycle. The E4 protein, strongly expressed in productive infections, can prove a transforming infection when it is absent. In recent years, detection of the TERC gene and oncogenetic microRNAs expressed early in carcinogenesis before clinical findings show great promise in differentiating lesions likely to progress to cancer. In conclusion, biomarkers are more powerful instruments to enhance early pre-cervical cancer lesions diagnosis, which allow better prognosis and more reliable treatment.

Concordance in HPV Detection Between Self-Collected and Health Provider-Collected Cervicovaginal Samples Using careHPV in Tanzanian Women.

PURPOSECervical cancer screening is one of the strategies to prevent the disease among women at risk. Human papillomavirus (HPV) DNA testing is increasingly used as the cervical cancer screening method because of its high sensitivity. Self-collection of cervical specimens has the potential to improve participation. However, there is only limited information on comparison between self-collected and provider-collected samples with regard to detection of high-risk HPV using the careHPV method. The study aimed to compare HPV detection by careHPV in self-collected and provider-collected cervical samples and to assess the acceptability of self-collection techniques.MATERIAL AND METHODSWomen attending cervical cancer screening clinics at Ocean Road Cancer Institute, Kilimanjaro Christian Medical Centre or Mawenzi Hospital in Tanzania were included in the study. They underwent a face-to-face interview, HIV testing, and collected a self-sample using Evalyn Brush. Subsequently, they had a cervical sample taken by a health provider. Both samples were tested for high-risk HPV DNA using careHPV.RESULTSOverall, 464 women participated in the study. The high-risk HPV prevalence was 19.0% (95% CI, 15.6 to 22.9) in the health provider samples, but lower (13.8%; 95% CI, 10.9 to 17.3) in the self-collected samples. There was a good overall agreement 90.5% (95% CI, 87.5 to 93.0) and concordance (κ = 0.66; 95% CI, 0.56 to 0.75) between the two sets of samples. Sensitivity and specificity were 61.4% (95% CI, 50.4 to 71.6) and 97.3% (95% CI, 95.2 to 98.7), respectively, varying with age. Most women preferred self-collection (79.8%).CONCLUSIONOverall, self-sampling seems to be a reliable alternative to health-provider collection and is acceptable to the majority of women. However, instructions on proper procedures for sample collection to the women are important.

Reduction of HPV16/18 prevalence in young women after eight years of three- and two-dose vaccination schemes

BackgroundRecommendations for human papillomavirus vaccination have relied on immunogenicity studies and efficacy results derived from adult women. Insufficient information exists regarding HPV effectiveness in vaccinated girls as they become sexually active, regardless of dose scheme. We aimed to compare the prevalence of high-risk HPV between unvaccinated and vaccinated young women eight years after immunization. MethodsAfter eight years, we recontacted women who received two-dose of bivalent or three-dose—either bivalent or quadrivalent—, HPV vaccine when aged 9–10 years-old as part of a clinical trial. Additionally, we recruited a contemporaneous unvaccinated woman group for comparison. Only those sexually active were included. High-risk HPV DNA was determined in urine samples and compared across groups. ResultsThe prevalence of HPV16/18 types was 6.8% (95 %CI 3.2–14.1%) in the unvaccinated (n = 6/88), 1.1% (95 %CI 0.2–5.8%) in the three-dose (n = 1/93), and 0.0% (95 %CI 0.0–7.0%) in the two-dose group (n = 0/51). ConclusionHPV vaccination, with two-dose of bivalent or three-dose schemes—either with the bivalent or quadrivalent vaccine—, was associated with a lower prevalence of HPV16/18 types eight years after primary immunization.

CLINICOPATHOLOGIC FEATURES OF HUMAN PAPILLOMAVIRUS–ASSOCIATED ORAL EPITHELIAL DYSPLASIA

<h3>Background</h3> There has been growing acceptance by the oral pathology community that high-risk human papillomavirus (HPV) is associated with a subset of oral epithelial dysplasias (OEDs), but there is lack of consensus on the diagnostic criteria for HPV OED. This study describes the clinicopathologic features of this disease with the intention of adding to the current pool of knowledge to clarify diagnostic criteria and elucidate its clinical significance. <h3>Method</h3> Automated p16 and viral capsid immunohistochemistry, as well as high-risk HPV DNA and RNA in situ hybridization were undertaken in 71 archival samples from 40 patients diagnosed with HPV OED and 11 samples demonstrating similar histomorphological features. Ploidy analysis was undertaken on a subset of samples. <h3>Results</h3> The male:female ratio was 3.4:1. Five patients presented with adjacent associated invasive carcinoma, and in 4 patients there was subsequent malignant transformation. Histologic features of viral infection did not consistently colocalize with p16, and DNA or RNA in situ hybridization and were also present at varying degrees in the cases deemed HPV-negative. Capsid protein was present in 11 cases. Seven cases were DNA negative but assessed RNA positive. Of the cases subject to ploidy analysis, 9 were diploid and 6 were aneuploid. Two cases were reclassified as papillomas. <h3>Conclusions</h3> Standardized diagnostic criteria are required to differentiate HPV OED from histologic mimics. Further research is necessary to determine the histologic and ancillary factors that may be useful in predicting malignant transformation.

Long-term cervical precancer outcomes after a negative DNA- or RNA-based human papillomavirus test result

Cervical cancer, a preventable disease associated with the human papillomavirus, is responsible for significant morbidity and mortality globally. Primary human papillomavirus testing is more sensitive in detecting precancerous cervical lesions than cytologic screening and can be conducted using either DNA- or RNA-based assays. Screening programs must select the most appropriate assay from several available assays for their population. It is not yet known whether these assays perform equivalently in the long term, particularly among women with a negative human papillomavirus test result. This study aims to compare long-term safety after a negative human papillomavirus test result across both DNA- and RNA-based testing assays. This study aimed to compare long-term high-grade cervical intraepithelial neoplasia (grade 2 or higher and grade 3 or higher) outcomes of 2 DNA-based assays (Digene Hybrid Capture 2 High-Risk HPV DNA Test and cobas 4800 HPV Test) and 1 messenger RNA-based assay (Aptima HPV Assay) using data from the Human Papillomavirus For Cervical Cancer Trial-DECADEl (FOCAL-DECADE) cohort, by first comparing the positive and negative rates between the assays and then investigating the cumulative incidence of cervical intraepithelial neoplasia grade 2 and higher and grade 3 or higher detection among participants in the FOCAL DECADE cohort over follow-up according to human papillomavirus testing assays. The FOCAL Trial was a randomized controlled trial that evaluated human papillomavirus testing for primary cervical cancer screening. The FOCAL-DECADE cohort subsequently followed FOCAL Trial participants passively through the British Columbia Cervix Screening Program Database for approximately 10 years after the FOCAL Trial study exit to examine the rates of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher. For this study, eligible participants had baseline human papillomavirus-negative results from at least 1 assay and had 1 or more cytologic screens after baseline (9509 participants for DNA-based and 3473 participants for DNA- vs RNA-based assay comparisons). We constructed cumulative incidence curves and compared the hazard ratios for cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher detection according to the assays. Over 10 years of follow-up, the cumulative incidence of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ between the DNA-based assays (hazard ratio, 0.95; 95% confidence interval, 0.84-1.06; P=.35 and hazard ratio, 0.82; 95% confidence interval, 0.66-1.01; P=.06 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively) or between the DNA- and RNA-based assays (hazard ratio, 0.97; 95% confidence interval, 0.87-1.06; P=.48 and hazard ratio, 0.94; 95% confidence interval, 0.79-1.13; P=.52 for cervical intraepithelial neoplasia grade 2 or higher and cervical intraepithelial neoplasia grade 3 or higher, respectively). Among participants who tested negative for human papillomavirus at baseline, the long-term risk of cervical intraepithelial neoplasia grade 2 or higher and grade 3 or higher did not significantly differ regardless of whether DNA- or RNA-based human papillomavirus testing assays were used. Screening program decision makers can be confident that for women who test negative for human papillomavirus, DNA- and RNA-based assays exhibit similar cervical intraepithelial neoplasia grade 2 or higher outcomes over several years.

Assessment of alternative approaches of primary cervical cancer screening among women in low-income environments

Alternative techniques for detecting cancer of the cervix uteri alongside its early precancerous lesions still remain necessary for low income environments since morbidity and mortality due to cervical cancer continues to be on the rise. We recruited one thousand and seventy-seven women aged 15-55 years from selected study hospitals in Eastern Uganda and examined them using Papanicolaou (Pap) smear, direct visual inspection with 5% acetic acid solution (VIA), and human papillomavirus (HPV) DNA testing. Study participants detected with high-grade lesions (HSIL) or cancer cells on Pap smear test, positive VIA test (acetowhite lesions, cervical ulcer or growth), and positive high-risk HPV DNA (relative light units (RLU) were immediately scheduled for colposcopy and cervical biopsy. Of the forty percent of the women confirmed with pap smear positive, 43 of the 63 women had invasive carcinoma (68.3%), while 89 out of 137 women with confirmed biopsy were diagnosed with high grade CIN (CIN2,3) (65%). DVI identified 46 of 63 carcinomas (73%) as well as 47 of 74 high grades CIN (CIN 2, 3) (64%). There was a variation in HPV DNA results due to the cutoff value considered in defining the final result. HPV DNA of high-risk HPV types was detected 39 (61.9%) out the 63 women diagnosed invasive cervical cancer, while 66 (73.3%) or 46 (51%) was detected in the biopsy of women diagnosed with high grade CIN (CIN 2,3). Similarity in identification of high-grade cervical abnormalities was registered by the testing methods. Both VIA and HPV genetic testing methods diagnosed similar numbers of high grade CIN 2,3 and invasive cancer cases as Pap smears. Nevertheless, individual test methods categorized study participants with no cervical disease as being positive. Key words: Visual inspection with acetic acid (VIA), cervical intraepithelial neoplasia (CIN), human papillomavirus (HPV).

Identification of High-Risk Human Papillomavirus DNA, p16, and E6/E7 Oncoproteins in Laryngeal and Hypopharyngeal Squamous Cell Carcinomas.

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.