Human Papillomavirus Detection Methods Research Articles

Dual lateral flow assay based on PdRu nanocages for human Papillomavirus detection

Cervical cancer is one of the most common gynecological malignancies, with the vast majority of which being caused by persistent infection with Human Papillomavirus (HPV) 16 and 18. The current available HPV detection methods are sensitive and genotyped but are restricted by expensive instruments and skilled personnel. The development of an easy-to-use, rapid, and cost-friendly analysis method for HPV is of great need. Herein, hollow palladium-ruthenium nanocages modified with two oligonucleotides (PdRu capture probes) were constructed for genotyping and simultaneous detection of target nucleic acids HPV16 and HPV18 by dual lateral flow assay (DLFA). PdRu capture probes were endowed with bi-functions for the first time, which could be used to output signals and hybridize target nucleic acids. Under optimized conditions, the PdRu based-DLFA with detection limits of 0.93 nM and 0.19 nM, respectively, exhibited convenient operation, and high sensitivity. Meanwhile, the DLFA achieved excellent rapid detection within 20 min, which was attributed to capture probes that can be directly bound to amplification-free target nucleic acids. Therefore, the development of PdRu-based DLFA can be utilized for rapid, sensitive, and simultaneous genotyping detection of HPV16 and HPV18, showing great application for nucleic acid detection.

Anal human papillomavirus (HPV) disagreement by Linear Array compared to SPF10 PCR-DEIA-LiPA25 system in young sexual minority men

IntroductionYoung sexual minority men (SMM) bear the greatest burden of anal human papillomavirus (HPV) infections. We assessed anal HPV genotype discordance between the Linear Array (LA) and SPF10 PCR-DEIA-LiPA25 (LiPA25). MethodsDiscordance was assessed between LA and LiPA25 using self-collected anal swabs from 120 SMM aged 18–29 who were recruited in 2014–2016. Multiple-type infection was explored as a potential confounder of testing agreement, along with clinical and behavioral factors such as HIV status, syphilis status, incarceration history, health insurance coverage, having 3 or more sex partners in the past 6 months, and co-infection with HPV-16. ResultsSignificant discordance was found for HPV-6, -11, -16, -31, -42, -54, and -59. Exploratory analyses suggest higher prevalence of genotype discordance in those living with HIV, those with 3 or more sex partners, and those who were positive for 4 or more HPV types. ConclusionsOur results highlight the importance of HPV detection methods which may inform different interpretations of research assessing anal HPV natural history among SMM at highest risk for HPV.

Prevalence of human papillomavirus in oral cancer in Asia: A systematic review and meta-analysis.

To determine the prevalence of human papillomavirus (HPV) in oral squamous cell carcinoma (OSCC) across Asian countries, focusing on South and Southeast Asia. A systematic search of four databases-MEDLINE/PubMed, EMBASE, Scopus, and ProQuest-was conducted to identify observational studies published between January 2013 and December 2023. The pooled prevalence of HPV was estimated using random-effects models, and subgroup analysis was performed to investigate the source of heterogeneity. A total of 77 studies were included, comprising 7289 OSCC cases from 11 countries. The pooled HPV prevalence in OSCC was 23.1% (95% CI 17.9-28.7, I2 = 96.7%). South Asia had the highest prevalence (27.1%), followed by East Asia (19.4%), and Southeast Asia (16.7%). Two subtypes were commonly reported: HPV-16 (9.1%) and HPV-18 (5.1%). Anatomical subsites, buccal mucosa (34.0%), and floor of the mouth (33.2%) had similar ranges of HPV prevalence. All studies exhibited a high degree of heterogeneity, with the OSCC location and risk of bias identified as potential sources of heterogeneity. Due to the high HPV prevalence in OSCC in Asia, HPV detection in routine pathology practice is recommended. Future studies should be conducted in multicentre settings using similar HPV detection methods and reporting detailed demographic and clinical information on oral sub-sites.

Is Concentrated Urine PCR Test Valuable to Detect Genital HPV Infection [ID 2683587

INTRODUCTION: Human papillomavirus (HPV) is the leading cause of cervical cancer and early detection is crucial for effective prevention. The standard HPV detection method, cervical smear PCR, entails discomfort and deters many women. Therefore, it is challenging to screen large populations for HPV from cervical smear samples. In this study, we investigated the sensitivity of detecting HPV by PCR in concentrated urine samples. METHODS: Urine and cervical smear samples were collected from 126 patients (ages 20–35) at Acibadem Altunizade Hospital. Urine samples were concentrated by a tool (MyMagiCon). The presence of HPV DNA in cervical smear and urine samples was determined by PCR. RESULTS: Among 126 patients, HPV was detected in 57 either in at least one of the sample types (cervical smear, urine, and concentrated urine). Among all HPV-positive patients, HPV was identified in 87.7% of swab samples, 86% of concentrated urine samples, and only 73.7% of unconcentrated urine samples. The χ2 test comparing cervical smear and concentrated urine samples yielded a Kappa value of 0.78 (95% confidence), indicating strong statistical correlation within this study. Additionally, PCR from concentrated urine samples, identified six HPV-positive samples that were HPV negative in cervical smear samples of the same patients. CONCLUSION: It was possible to identify HPV in concentrated urine samples by PCR with a sensitivity almost equal to cervical smear sampling. Since obtaining urine is much easier than obtaining cervical smear samples, this may enable easy screening of large populations for HPV. This may have a big effect in the prevention of cervical cancer.

Human Papillomavirus (HPV16 and HPV18) Infection; Pathogenesis, Vaccination, and Detection by Loop-Mediated Isothermal Amplification with Lateral Flow Dipstick Tests: A Review

Context: Human papillomavirus (HPV) infections contribute to the cause of 15% - 20% of all human cancers. This review aims to examine and provide updated information on various aspects, with a particular focus on topics that are of interest to dermatologists. Evidence Acquisition: Using published studies, the pathogenicity of HPV was investigated. Subsequently, the existing vaccines were explored, followed by a review of the loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) method. Results: For HPV detection, the polymerase chain reaction (PCR), self-sustained sequence replication (3SR), strand displacement amplification (SDA), and nucleic acid sequence-based amplification (NASBA) were used. These methods can have good detection but still have problems. In comparison with nested PCR, the detection of HPV16 and HPV18 using LAMP-LFD has higher sensitivity. Conclusions: Loop-mediated isothermal amplification-lateral flow dipstick is a simple and rapid method for the specific and sensitive detection of HPV. Thus, along with the previous HPV16 and HPV18 diagnostic tools, LAMP-LFD might be useful in field studies or local hospitals.

The establishment of a multiplex fluorescent polymerase chain reaction coupled with capillary electrophoresis analysis technology enables the simultaneous detection of 16 genotypes of human papillomavirus.

The detection and accurate genotyping of human papillomavirus (HPV) infection is critical for preventing and effectively treating cervical cancer. A multiplex fluorescent polymerase chain reaction (PCR) coupled with a capillary electrophoresis method was developed for the simultaneous detection of the 16 most prevalent HPV genotypes. Twenty-five pairs of primers were ultimately selected to ensure that both E and L regions of nine HPV genotypes, as well as the Eregions of seven HPV genotypes could be accurately amplified. This method enables the simultaneous detection and differentiation of 16 HPV genotypes in a single closed-tube reaction, accurately distinguishing products with molecular weight differences >1 bp through capillary electrophoresis. This method demonstrated exceptional accuracy, specificity, and repeatability with a detection limit of 10 copies/μL for all 16 HPV genotypes. Furthermore, 152 cervical swab specimens were obtained to compare the disparities between this approach and Cobas 4800 HPV detection method. The concordance rate and κ value were 90.1% and 0.802, respectively, indicating a high level of agreement. The established detection method was successfully applied to cervical swab specimens for determining HPV genotypes across all levels of cervical lesions, HPV52, 56, 16, and 59 were found to be most prevalent with infection rates of 10.8%, 9.1%, 6.5%, and 6.2%, respectively. This study has successfully established a detection method capable of simultaneously identifying 16 HPV genotypes. This approach can be further applied to HPV vaccine research and surveillance, with the potential for broad applications.

Development and validation of real-time recombinase polymerase amplification-based assays for detecting HPV16 and HPV18 DNA.

Cervical cancer is the fourth leading cause of cancer-related death among women worldwide. Persistent human papillomavirus (HPV) infection is the principal cause of cervical cancer, with HPV16 and HPV18 accounting for about 70% of cases worldwide. Cervical screening is an effective secondary measure for preventing cervical cancer. Testing for HPV DNA is becoming increasingly important in cervical cancer screening. The existing PCR-based HPV detection technology has several disadvantages: the assays are time-consuming, and sophisticated equipment is required to control the temperature cycles. These drawbacks have led to the development of detection technologies based on isothermal amplification. Here, we present real-time recombinase polymerase amplification (RPA-exo)-based assays for single genotyping of either the E7 or the L1 segment of HPV16 or HPV18. These assays were highly sensitive, able to detect HPV in all clinical samples with Ct values below 34, and yielded results within 25 min. A dual-detection system capable of detecting both HPV16 and HPV18 in a single reaction was also developed based on the L1 gene. It has a limit of detection of approximately 10,000 copies of each genotype per reaction. The assays were validated with DNA extracted from 36 biopsy specimens and 42 exfoliated cell samples from 43 patients with cervical lesions at different stages. The RPA-exo system is a promising clinical detection platform with the advantages of yielding results rapidly and operating at a constant temperature, while being cost-effective and easy to use. IMPORTANCE HPV DNA screening is an effective approach for the prevention of cervical cancer. The novel real-time recombinase polymerase amplification-based HPV detection systems we developed constitute an improvement over the HPV detection methods currently used in clinical practice and should help to extend cervical cancer screening in the future, particularly in point-of-care test settings.

Human papillomavirus prevalence in pregnant women living with human immunodeficiency virus infection: a scoping review of the literature.

Studies already pointed out the increased risk of human papillomavirus (HPV) positivity and the implied risk of cervical dysplasia and even cervical carcinoma inpregnant women with human immunodeficiency virus (HIV) infection. Nevertheless, due to less data there is still no standardised and expanded screening for this high-risk group. Two online databases (PubMed, EMBASE) were used to identify eligible studies. Results are shown in percentages. Wherever useful the arithmetic mean was calculated. Seven studies were included. Pregnant WLWH showed HPV prevalence between 34 and 98.4 %. Different sensitivity and specificity among PCR methods for HPV detection could be a reason for the large range concerning HPV prevalence. Risk factors like Age, Smoking, Sexuality, HIV status and education level should always be taken into account. Association between HPV prevalence and level of CD4 cells or HIV virus load was seen. In which way use of Antiretroviral Therapy (ART) could decries the risk for HPV infections is still discussed. When cytology was performed only few high-grade squamous intraepithelial lesion (HSIL) were found. Standardisation and expansion of preventive screening for cervical dysplasia and carcinoma for pregnant WLWH is necessary. Then better comparability of the data will also be achieved.

Coupling CRISPR/Cas12a and Recombinase Polymerase Amplification on a Stand-Alone Microfluidics Platform for Fast and Parallel Nucleic Acid Detection.

Timely identification of human papillomavirus (HPV) infection is crucial for the prevention of cervical cancer. Current HPV detection methods mainly rely on polymerase chain reaction (PCR), which often requires bulky equipment and a long assay time. In this work, we report a heating-membrane-assisted multiplexed microfluidics platform that couples recombinase polymerase amplification (RPA) and CRISPR technology (termed M3-CRISPR) for fast and low-cost detection of multiple HPV subtypes. The heating membrane can provide convenient temperature control for the on-chip RPA and CRISPR assays. This stand-alone system allows simultaneous detection of HPV16 and HPV18 with high specificity and detection sensitivity (0.5 nM and 1 × 10-18 M for unamplified and amplified plasmids, respectively) in 30 min with a fluorescence-based readout. Furthermore, we introduced an optimized lateral flow dipstick (LFD) into the portable system to allow visualized detection of HPV DNA. The LFD-based readout also reached a detection sensitivity of 1 × 10-18 M for amplified plasmids and realized successful detection of HPV subtypes in the clinical samples. Finally, we established an automatic microfluidic system that enables the sample-in-answer-out detection of HPV subtypes. We believe that this fast, convenient, and affordable molecular diagnostic platform can serve as a useful tool in point-of-care testing of HPV or other pathogens.

Integrating CRISPR-Cas12a into a Microfluidic Dual-Droplet Device Enables Simultaneous Detection of HPV16 and HPV18.

Fast, simplified, and multiplexed detection of human papillomaviruses (HPVs) is of great importance for both clinical management and population screening. However, current HPV detection methods often require sophisticated instruments and laborious procedures to detect multiple targets. In this work, we developed a simple microfluidic dual-droplet device (M-D3) for the simultaneous detection of HPV16 and HPV18 by combining the CRISPR-Cas12a system and multiplexed recombinase polymerase amplification (RPA) assay. A new approach of combining pressure/vacuum was proposed for efficient droplet generation with minimal sample consumption. Two groups of droplets that separately encapsulate the relevant Cas12a/crRNA and the fluorescent green or red reporters are parallelly generated, followed by automatic imaging to discriminate the HPV subtypes based on the specific fluorescence of the droplets. The M-D3 platform performs with high sensitivity (∼0.02 nM for unamplified plasmids) and specificity in detecting HPV16 and HPV18 DNA. By combining the RPA and Cas12a assay, M-D3 allows on-chip detection of HPV16 and HPV18 DNA simultaneously within 30 min, reaching a detection limit of 10-18 M (∼1 copy/reaction). Moreover, the outstanding performance of M-D3 was validated in testing 20 clinical patient samples with HPV infection risk, showing a sensitivity of 92.3% and a specificity of 100%. By integrating the dual-droplet generator, CRISPR-Cas12a, and multiplexed RPA, the M-D3 platform provides an efficient way to discriminate the two most harmful HPV subtypes and holds great potential in the applications of multiplexed nucleic acid testing.

Evaluation of the Novaplex II HPV28 Detection Assay for HPV Typing in Formalin-Fixed, Paraffin-Embedded Tissues

Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed, paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. Results of the Novaplex II HPV28 Detection (Novaplex) assay were compared with those from the reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. Novaplex showed high type-specific concordance with the reference method for HPV16/18, 9 types targeted by the Gardasil 9 vaccine, 14 high-risk types, and 21 types covered by comparison assays. The rate of inadequate samples was low in both approaches (reference, 3.4%; Novaplex, 1.7%). The proportion of discrepant types was less than 3.5% and positive concordance was greater than 75.0%. Furthermore, the type-specific positive agreement (92.0% to 98.0%), negative agreement (96.0% to 99.0%), and accuracy (97.0% to 99.0%) was high. Cohen's κ ranged from 0.86 to 0.89, indicating excellent agreement between Novaplex and reference assays. The results show that Novaplex is a suitable method for detection of HPV in FFPE tissues.

QUANTITATIVE AND QUALITATIVE ANALYSIS OF P16 IN HPV POSITIVE AND HPV NEGATIVE ORAL SQUAMOUS CELL CARCINOMA- AN IMMUNOHISTOCHEMICAL STUDY

Diagnosing and prognosis of oral cancer precursors is challenging. This study investigates the correlation quantitative and qualitative expression of p16 in HPV positive and HPV negative OSCC cases .Human Papillomavirus (HPV) is believed to promote the oncogenic process and the correlation between viral oncoproteins and dysfunction of p16 tumour suppressor protein in oral lesions has been established in many studies .Concerning involvement of risk factors ,clinical course of the disease ,and prognosis there are strong indications arguing that the HPV positive OSCC may represent a separate tumour entity. Looking for a surrogate marker ,which in further epidemiological studies could replace the laborious and expensive HPV detection methods this study was conducted which include 30 cases of HPV positive and 30 HPV negative OSCC and 10 controlled cases of HPV colon were taken and p16 was evaluated according to distribution extent and degree of intensity.Based on the staining intensity among the HPV negative cases the staining intensity score was 1 in 80 percent of the subjects whereas in the HPV positive cases 63.3% were having Score 3 and 26.7% were having Score 2. The difference between HPV+ and HPV- was statistically significant and was analyzed using chi square test.Based on the semi quantitative analysis among the HPV negative cases the staining was negative in 80 percent of the subjects whereas in the HPV+ 63.3% were having diffuse staining and 30.0% were having focal staining. The difference between HPV positive and HPV negative was statistically significant when analyzed using chi square test.These data indicated that p16 is technically simple immunohistological marker applicable for routine pathological histology.

Prediction value with a novel and accurate tissue-based human papillomavirus detection method in low-grade squamous intraepithelial lesions.

BackgroundThe progression rate from CIN1 to CIN3 is 9.0% and that for invasive cancer is 1.0%. The large majority of CIN1 lesions regress spontaneously, and the treatment of CIN1 is still controversial.AimsThe aim of this study is to investigate the responsible HPV genotype in the low‐grade SILs, then to predict the presence of high‐grade SILs, and determine whether further treatment is needed.MethodsWe use the methods of manual microdissection with FFPE tissue specimens and the E6/E7 uniplex polymerase chain reaction (PCR) to detect HPV in the lesions.ResultsThe HPV test was performed on 72 biopsy tissue specimens, and 55 (76.4%, 55/72) of them were HPV positive. Nine (16.4%, 9/55) of them escalated to CIN2 after LEEP or cervical conization, and 46 (83.6%, 46/55) were still CIN1. There were 17 (23.6%, 17/72) cases with HPV‐negative results in cervical biopsy tissues.HPV test of cervical biopsy diagnosed with CIN1 has a positive predictive value of 16.4% in the presence of CIN2 or higher lesions, a negative predictive value of 94.1%, a specificity of 25.8%, and a sensitivity of 90.0%. HPV test of cervical biopsy tissues for the prediction of HPV infection in LEEP or cone surgery tissues had a positive predictive value of 80.0%, a negative predictive value of 82.3%, a specificity of 56.0%, and a sensitivity of 93.6%.ConclusionsIt is the first time that we have detected HPV genotype in the low‐grade SILs by the methods of manual microdissection with FFPE tissue specimens and the E6/E7 uniplex PCR. Patients with cervical biopsy tissue diagnosed with CIN1 and with a negative or only low‐risk HPV type result can be considered for follow‐up. Conversely, in cases of cervical biopsy tissue diagnosed with CIN1 positive for high‐risk HPV, surgery or a close follow‐up program can be selected.

Decreased CD1a + and CD83 + cells in tonsillar squamous cell carcinoma regardless of HPV status.

Dendritic cells (DCs) are specialized antigen-presenting cells that play a critical role in the immune response against human papillomavirus (HPV) infection, and represent a therapeutic target in cancer.Objective:To identify and quantify DCs in tonsillar squamous cell carcinoma (TSCC) under the influence of HPV infection.Methodology:CD1a and CD83 antibodies were used to identify immature dendritic cells and mature dendritic cells by immunohistochemistry in 33 primary TSCC and 10 normal tonsils (NTs), respectively. For the TSCC samples, the number of DCs per area was evaluated in the intra- and peritumoral compartments. For the NTs, the quantification of DCs was evaluated in the intra- and peritonsillar compartments. HPV detection methods were determined according to the ASCO Clinical Practice Guidelines from the College of American Pathologists Guideline (2018).Results:There were fewer intratumoral CD1a+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.05). In the peritumoral compartment, there were fewer CD83+ DCs in the HPV-positive and HPV-negative TSCC groups than in the NT group (p<0.001). The quantification of DCs subtypes showed no statistical differences between HPV-positive and HPV-negative TSCC groups (p>0.137). Patients with HPV-positive TSCC had significantly better overall survival rate than those with HPV-negative TSCC (p=0.004).Conclusion:Tumor activity contributes to DC depletion regardless of intralesional HPV positivity. An improved prognosis has been reported in patients with HPV-positive TSCC.

Comparison of oral human papilloma virus detection methods among Hispanic adults

ObjectivesOral human papilloma virus (HPV) infection is associated with nearly three‐quarters of all oropharyngeal cancers in the United States. Research also suggests its association with periodontal disease. There are limited studies evaluating differences in HPV detection methods; however, oral rinse is considered the most sensitive detection method. We compared HPV detection by self‐collected oral rinse versus self‐collected cytobrush and assessed whether the strength of association between periodontitis and HPV is modified by the collection method.Materials and MethodsData from a cross‐sectional study of Hispanic adults in Puerto Rico (n = 346) who provided oral rinse and cytobrush samples for oral HPV detection and were clinically evaluated for periodontitis. The agreement between the oral mouthwash and cytobrush methods was assessed using the Kappa (κ) statistic. Logistic regression models were used to determine if the association between HPV infection and other risk factors varied by oral sample collection method.ResultsHPV prevalence was slightly higher using cytobrush than oral rinse (5.8% vs. 4.3%). The sensitivity of cytobrush to detect oral HPV was 64.7%, and the specificity was 97.4%. We observed a κ of 0.61 (95% confidence interval [CI]: 0.45–0.78), indicative of fair to good agreement between the two collection methods. The association between oral HPV infection and periodontitis severity was stronger when using the oral rinse collection method (odds ratio [OR] = 3.23, 95% CI: 1.06–9.84); the association was not statistically significant for cytobrush (OR = 1.96, 95% CI: 0.68–5.65).ConclusionsThese findings support the significance of choosing the most suitable collection method in oral HPV‐related studies. Selecting the most appropriate collection method is an essential criterion in oral HPV‐related studies.

Low Frequency of Human Papillomavirus in Strictly Site-Coded Oral Squamous Cell Carcinomas, Using the Latest NHI/SEER-ICD Systems: A Pilot Observational Study and Critical Review.

Simple SummaryThe incidence of oropharyngeal squamous cell carcinomas (OPSCCs) has increased in the last decades, and this seems to be correlated to the infectious epidemiological trend of human papillomavirus (HPV). The prevalence of HPV-positive OPSCCs is approximately 70%, with involvement mainly of the tonsillar area. On the role of HPV in oral squamous cell carcinoma (OSCC), very few studies have investigated the prevalence of HPV in strictly site-codified OSCC, excluding the base of the tongue as distinct oropharyngeal entity. As a result, an inappropriate estimation of HPV infection in OSCC has been observed. We investigated HPV status, using a combination of detection methods, in a sample of 40 subjects with OSCC coded by the latest site classifications. Moreover, we performed a critical review of the studies with the same outcomes. The main finding of our investigation was a low frequency of HPV-positive OSCC, suggesting no significant HPV role in strictly oral carcinogenesis.The aim of this study was to evaluate HPV status in oral squamous cell carcinoma (OSCC), as coded by the latest classifications and applying a combination of detection methods used in clinical practice. Forty-two patients with suspect OSCC were consecutively recruited. Patients underwent an incisional biopsy for histological OSCC diagnosis and HPV identification by PCR DNA and p16 IHC. All lesions were coded by the latest ICD-0-3.2 site/histology classifications, as proposed for OSCC by the National Cancer Institute Surveillance, Epidemiology and End Results Programs. Moreover, a comparative analysis review, critically evaluated by the same site-coded systems and HPV detection methods, was performed. In 40 confirmed cases of OSCC, the frequency of HPV infection was 10% (4/40). Among positive patients, two cases were PCR DNA/p16 IHC positive (high-risk HPV 51, high-risk HPV 67), two cases were PCR DNA positive/p16 IHC negative (high-risk HPV 31 + 68, high-risk HPV 66). Applying the latest site coding systems for OSCC, the frequency of HPV infection in this study and in similar, reviewed investigations was low (from 3.3% to 12.5%). These results suggested no significant HPV role in oral carcinogenesis, particularly where an updated site-coded classification of OSCCs (categorically excluding the base of the tongue) had been performed.

Diagnostic Accuracy of HPV Detection in Patients with Oropharyngeal Squamous Cell Carcinomas: A Systematic Review and Meta-Analysis.

The aim of the study was to evaluate the diagnostic accuracy of Human Papillomavirus (HPV) techniques in oropharyngeal cancer. PubMed, EMBASE, the Cochrane Library and clinicaltrials.org were systematically searched for studies reporting methods of HPV detection. Primary outcomes were sensitivity and specificity of HPV detection. In this case, 27 studies were included (n = 5488, 41.6% HPV+). In this case, 13 studies evaluated HPV detection in tumour tissue, nine studies examined HPV detection in blood samples and five studies evaluated HPV detection in oral samples. Accuracy of HPV detection in tumour tissue was high for all detection methods, with pooled sensitivity ranging from 81.1% (95% CI 71.9–87.8) to 93.1% (95% CI 87.4–96.4) and specificity ranging from 81.1% (95% CI 71.9–87.8) to 94.9% (95% CI 79.1–98.9) depending on detection methods. Overall accuracy of HPV detection in blood samples revealed a sensitivity of 81.4% (95% CI 62.9–91.9) and a specificity of 94.8% (95% CI 91.4–96.9). In oral samples pooled sensitivity and specificity were lower (77.0% (95% CI 68.8–83.6) and 74.0% (95% CI 58.0–85.4)). In conclusion, we found an overall high accuracy for HPV detection in tumour tissue regardless of the HPV detection method used. HPV detection in blood samples may provide a promising new way of HPV detection.

HPV in the malignant transformation of sinonasal inverted papillomas: A meta-analysis.

To date, there is still a significant debate on the role of human papilloma virus (HPV) infection in transformation of inverted papillomas (IPs) to squamous cell carcinoma (SCC). This study was designed to determine if the presence of HPV in a sinonasal IP increases the risk of malignant transformation to IPSCC. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 19 high-quality case-control and cohort studies with tissue-diagnosed IP or IPSCC and HPV diagnosis were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method with correction for random effects. Subgroup, publication bias and a sensitivity analyses were also performed. Nineteen studies with minimal bias met the inclusion criteria for quality and identified HPV infection in an IP. The pooled data revealed a strong association with progression to malignancy with an unweighted, pooled OR of 2.38 (CI95 1.47 to 3.83) and a weighted OR of 2.80 (CI95 1.42 to 5.51). Sensitivity analysis revealed that no single study contributed significantly to our pooled OR calculations (ORs 2.52 to 3.57). Subgroup analyses stratified by publication date, nucleic acid target, HPV detection method and type, sample size, and region all demonstrated a positive association of HPV with IPSCC. There appears to be a significant association between HPV infection and malignant transformation of IPs. While HPV testing is not currently the standard of care for IPs, these data suggest a link between the two and suggest further studies should be performed to identify a link between the virus and malignant transformation.

Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Simple SummaryThe causative role of human papillomavirus (HPV) in sinonasal squamous cell carcinoma (SNSCC) remains unclear and is hindered by small studies using variable HPV detection techniques. This meta-analysis aims to provide an updated overview of HPV prevalence in SNSCC stratified by detection method, anatomic subsite, and geographic region. From 60 eligible studies, an overall HPV prevalence was estimated at 26%. When stratified by detection method, HPV prevalence was lower when using multiple substrate testing compared to single substrate testing. Anatomic subsite HPV prevalence was higher in subsites with high exposure to secretion flow compared to low exposure subsites. HPV prevalence in SNSCC followed the global distribution of HPV+ oropharyngeal squamous cell carcinoma. Taken together, this meta-analysis further supports a role for HPV in a subset of SNSCCs.Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7–31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5–28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6–41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5–50.2) vs. low-exposure (15.1%, 95% CI 7.3–28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9–41.5) vs. low (Africa) (13.1, 95% CI 6.5–24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.

Detection of human papillomavirus in oropharyngeal squamous cell carcinoma.

Worldwide there has been a significant increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) etiologically attributed to oncogenic human papillomavirus (HPV). Reliable and accurate identification and detection tools are important as the incidence of HPV-related cancer is on the rise. Several HPV detection methods for OPSCC have been developed and each has its own advantages and disadvantages in regard to sensitivity, specificity, and technical difficulty. This review summarizes our current knowledge of molecular methods for detecting HPV in OPSCC, including HPV DNA/RNA polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), p16 immunohistochemistry (IHC), and DNA/RNA in situ hybridization (ISH) assays. This summary may facilitate the selection of a suitable method for detecting HPV infection, and therefore may help in the early diagnosis of HPV-related carcinoma to reduce its mortality, incidence, and morbidity.