Human Papillomavirus Type 16 DNA Research Articles

Enhanced CRISPR/Cas12a-based quantitative detection of nucleic acids using double emulsion droplets

Pairing droplet microfluidics and CRISPR/Cas12a techniques creates a powerful solution for the detection and quantification of nucleic acids at the single-molecule level, due to its specificity, sensitivity, and simplicity. However, traditional water-in-oil (W/O) single emulsion (SE) droplets often present stability issues, affecting the accuracy and reproducibility of assay results. As an alternative, water-in-oil-in-water (W/O/W) double emulsion (DE) droplets offer superior stability and uniformity for droplet digital assays. Moreover, unlike SE droplets, DE droplets are compatible with commercially available flow cytometry instruments for high-throughput analysis. Despite these advantages, no study has demonstrated the use of DE droplets for CRISPR-based nucleic acid detection. In our study, we conducted a comparative analysis to assess the performance of SE and DE droplets in quantitative detection of human papillomavirus type 18 (HPV18) DNA based on CRISPR/Cas12a. We evaluated the stability of SEs and DEs by examining size variation, merging extent, and content interaction before and after incubation at different temperatures and time points. By integrating DE droplets with flow cytometry, we achieved high-throughput and high-accuracy CRISPR/Cas12a-based quantification of target HPV18 DNA. The DE platform, when paired with CRISPR/Cas12a and flow cytometry techniques, emerges as a reliable tool for absolute quantification of nucleic acid biomarkers.

HPV testing versus p16 immunohistochemistry in oropharyngeal squamous cell carcinoma: results from the DAHANCA 19 study

Introduction The prognosis after primary (chemo-)radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) is affected by Human Papillomavirus (HPV) status, with a better prognosis in HPV-positive OPSCC. HPV-status is routinely assessed by p16 immunohistochemistry (IHC), but additional HPV DNA testing is debated. Also, there are numerous HPV genotypes, which prognostic role may need clarification. The purpose of this study was: (1) to test a custom-made targeted HPV next generation sequencing (NGS) panel in OPSCC, (2) to determine correlation with p16 IHC, and (3) to assess the impact of HPV DNA testing on outcome in the prospectively randomized clinical trial DAHANCA 19. Materials and methods We included 271 patients with OPSCC treated with primary (chemo-)radiotherapy in the DAHANCA 19 trial. Of these, 199 (73%) were p16-positive. HPV-status was determined by targeted HPV next generation sequencing (NGS), using a custom-made HPV genotyping panel. Results HPV was detected in 194 tumor samples. p16 IHC and NGS HPV status were concordant in 265 (98%) of 271 patients, whereas we did not detect HPV DNA in 5 p16-positive tumors. HPV16 accounted for 169 of 194 HPV-positive cases (87%). HPV genotypes 18, 31, 33, 35, and 59 were also detected. Loco-regional failure and overall survival were similar whether patients were separated by p16 IHC, or HPV DNA status (p < 0.0001 for all) and did not depend on HPV genotype (p = 0.9 and p = 0.7). Conclusion In the present study, HPV DNA testing or typing in a Danish OPSCC cohort did not add additional information to p16 IHC, the most widely used and accepted prognostic indicator.

The impact of the COVID-19 pandemic on the prevalence and genotype distribution of HPV infection in Beijing, China.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. The COVID-19 pandemic has greatly influenced on the HPV prevention project. The objective of this study was to examine the influence of the pandemic on HPV prevalence and genotype distribution in Beijing, China. A total of 44 401 genital swabs were obtained from outpatients at Peking Union Medical College Hospital during two distinct periods: the prepandemic stage from January 2017 to December 2019 and the pandemic stage from January 2020 to December 2022. During the prepandemic and pandemic stages, a total of 33 531 and 10 870 swabs were respectively collected. Fifteen high-risk HPV(HR-HPV) DNA type and a combination of two low-risk (LR-HPV) types (6/11) of genital swabs were detected to compare the HPV infection rates and genotype distributions in two stages. The results showed that the pandemic period witnessed a decrease in the overall HPV infection rate from 33.43% (11 245/33 531) to 29.43% (5527/18 780) compared to the prepandemic. There were statistically significant differences in infection rates between females and males (p < 0.05). Single infection was the predominant type while multiple infection was more prevalent in males than females in both prepandemic and pandemic periods. HR-HPV infection constituted the majority of infections and cannot be disregarded. The distribution of HR-HPV genotypes exhibited little variation before and after the outbreak, but there were some differences between females and males. HPV 16, 52, 58, 56, and 66 were the most commonly detected genotypes in females, whereas HPV 16, 52, 51, 58, and 18 were frequently detected in males. Additionally, HPV 6/11 exhibited a higher prevalence in males than in females. Notably, the age group of 31-40 years old exhibited the highest prevalence of HPV and the lowest infection rate was detected among individuals aged ≤20 years (p < 0.05), which remained relatively consistent before and during the pandemic. These findings underscore the importance of monitoring the trend of HPV epidemic and offer valuable insights for the prevention, treatment, and scientific investigation of HPV in the post-COVID-19 era.

A human papillomavirus whole genome plasmid repository: A resource for HPV DNA quality control reagents.

Well characterized reference reagents are useful for assay validation, proficiency/competency assessment, daily run controls, and to improve inter-laboratory comparisons. Synthetic human papillomavirus (HPV) DNA fragments and plasmid clones are available, but synthetic fragments include limited segments of the HPV genome and many HPV plasmids have interrupted coding regions or contain partial genomes. As a result, they are not compatible with all HPV DNA detection and typing assays. To address this need, we are establishing an HPV plasmid repository of HPV clones containing the whole genome of each type with no interruptions in coding regions. To date, HPV plasmid clones for 16 HPV types, (including all vaccine types and 14 types in clinical assays: HPV6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) have been constructed using a Gibson assembly method and validated by sequencing and the Novaplex HPV typing assay. The newly constructed HPV whole genome plasmids can serve as a quality control reagent resource for HPV DNA assays and are available for public health and research laboratories.

Prevalence of oral and blood oncogenic human papillomavirus biomarkers among an enriched screening population: Baseline results of the MOUTH study.

Human papillomavirus (HPV)-related oropharyngeal cancer screening is being explored in research studies, but strategies to identify an appropriate population are not established. The authors evaluated whether a screening population could be enriched for participants with oncogenic HPV biomarkers using risk factors for oral HPV. Participants were enrolled at Johns Hopkins Hospitals and Mount Sinai Icahn School of Medicine. Eligible participants were either men aged 30 years or older who had two or more lifetime oral sex partners and a personal history of anogenital dysplasia/cancer or partners of patients who had HPV-related cancer. Oral rinse and serum samples were tested for oncogenic HPV DNA, RNA, and E6 or E7 antibodies, respectively. Participants with any biomarker were considered at-risk. Of 1108 individuals, 7.3% had any oncogenic oral HPV DNA, and 22.9% had serum antibodies for oncogenic HPV E6 or E7. Seventeen participants (1.5%) had both oral and blood biomarkers. HPV type 16 (HPV16) biomarkers were rarer, detected in 3.7% of participants, including 20 with oral HPV16 DNA and 22 with HPV16 E6 serum antibodies (n=1 had both). In adjusted analysis, living with HIV (adjusted odds ratio, 2.65; 95% CI, 1.60-4.40) and older age (66-86 vs. 24-45years; adjusted odds ratio, 1.70; 95% CI, 1.07-2.70) were significant predictors of being at risk. Compared with the general population, the prevalence of oral HPV16 (1.8% vs. 0.9%), any oncogenic oral HPV DNA (7.3% vs. 3.5%), and HPV16 E6 antibodies (2.2% vs. 0.3%) was significantly elevated. Enrichment by the eligibility criteria successfully identified a population with higher biomarker prevalence, including HPV16 biomarkers, that may be considered for screening trials. Most in this group are still expected to have a low risk of oropharyngeal cancer.

AuPt nanoalloy with dual functionalities for sensitive detection of HPV16 DNA.

Human papillomavirus type 16 (HPV16), one of the high-risk types, is responsible for 53% of cervical cancers. The development of an early diagnostic approach with high sensitivity, low-cost, point-of-care testing (POCT) for HPV16 is urgent. In our work, a novel dual-functional AuPt nanoalloy-based lateral flow nucleic acid biosensor (AuPt nanoalloy-based LFNAB) was established with excellent sensitivity for detecting HPV16 DNA for the first time. The AuPt nanoalloy particles were prepared by a one-step reduction method, which was simple, rapid, and green. The AuPt nanoalloy particles retained the performance of initial Au nanoparticles owing to the catalytic activity enabled by Pt. Such dual-functionalities offered two kinds of detection alternatives (i.e., normal mode and amplification mode, respectively). The former is produced just by the black color from the AuPt nanoalloy material itself, and the latter is more color sensitive from its superior catalytic activity. The optimized AuPt nanoalloy-based LFNAB exhibited satisfactory quantitative ability in detecting the target HPV16 DNA in the range of 5-200 pM with a LOD of 0.8 pM at the "amplification mode". The proposed dual-functional AuPt nanoalloy-based LFNAB displayed great potential and promising opportunity in POCT clinical diagnostics.

Assesment Of Hpv Dna Positive İndividuals İn Sivas Province İn Terms Of Some Variables

Background: Cervical cancer is one of the most common cancers in women and causes death. Revealing the distribution of HPV prevalence and types in cervical cancer remains important for both treatment and vaccination strategies. The goal of this study is to determine the HPV DNA subtypes of women who are positive for Human Papilloma Virus (HPV) screening, and to evaluate their sociodemographic characteristics and cervical smear results. &#x0D; Methods: The study was conducted on 215 women who were directed to Sivas Cumhuriyet University Obstetry and Gynocology outpatient clinic by her gynocologists or family physicians between 2015-2018 years. A questionnary containing datas of patients about age, education levels and jobs of both spouses, smoking status, obstetric history and age of first sexual intercourse was filled out by the researcher. The data were analysed with SPSS (vers 23.0) program and significance level was taken as 0.05.&#x0D; Results: The most prevalent HPV types were type 16 and category of the others; with the rates of respectively 47% (n: 101), 40% (n: 86). The frequencies of ASCUS (undetermined atypical squamous epithelial cells), LGSIL (low-grade squamous intraepithelial lesion) and HGSIL (high-grade squamous intraepithelial lesion) were respectively found to be 7.9% (n: 17), 23.7% (n: 51) and 1.9% (n: 4). The relationship between HPV types and Pap Smear results was statistically significant (p: 0.011). There was no difference between patients and their spouses about education levels and occupations; and among patients on smoking status, menstrual patterns, age at first sexual intercourse and family planning methods and HPV types (p&gt; 0.05). In women above aged 55, only two types of HPV DNA were observed; which were type 16 and category of the others (p: 0.005). The relationship between abortion history and HPV types was found out to be significant (p: 0.016). &#x0D; Conclusion: This study has contributed to the literature by revealing the types of HPV which observed in Sivas province over a period of 3 years.

Detection and Genotyping of Papillomavirus by Real-Time PCR in Iraqi Patients

Background: Cervical cancer (CC) is linked to human papillomavirus (HPV). Globally, the prevalence and genotype distribution differ significantly. Objectives: The goal of this study was to find HPV 14, 16, 18, and 45 genotypes in urogenital swabs by using a real-time PCR amplification test for quantitative genotyping of HPV DNA types 16, 18, and 45 and for simultaneous quantitative detection of HPV DNA types 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68, for a total of 14 HPV genotypes. Methods: This case-control study included 86 cervical swabs from Iraqi women referred by the Al-Yarmook teaching hospital in Baghdad, Iraq. The ages of cases varied from 23 to 70 years and specimens were obtained between March 2020 and March 2021. The DNA was extracted for molecular assay. Fourteen HPV genotypes were detected using real-time PCR (16, 18, 45, 31, 33, 35, 39, 51, 52, 56, 58, 59, 66, and 68). The detection protocol was based on the commercial Kit V31-100/F FRT as follows. For each sample reaction, 10х(N+1) μL of PCR-mix-1-FRT HPV 14 was added into a new tube. Then, 5.0х(N+1) μL of PCR-mix-2 buffer and 0.5х(N+1) μL of TaqF DNA polymerase were added. The tubes were vortexed. Finally, the prepared tubes added 10 μL of DNA samples from test or control samples. The statistical analysis was conducted using the statistical package for SPSS and Excel 2016 software. Results: Genotype 16 had the highest frequency, followed by genotypes 45 (22%), 18 (14%), 35 and 59 (6%), 52 and 58 (4%), and 31 (2%), while genotypes 33, 39, 51, 56, 66, and 68 had the lowest frequency (1%). Conclusions: The real-time PCR was efficient for detecting and genotyping HPV-DNA and could help in earlier detection and clinical care of HPV-infected patients by reducing costs and workload.

A rare case of condyloma acuminatum caused by HPV73 and HPV33 infection

Condyloma acuminatum (CA) is a sexually transmitted disease caused by human papillomavirus (HPV) infection, mainly by HPV DNA types 6 and 11. Except for HPV16 and HPV18, CA caused by other intermediate or high-risk subtypes is rare in clinical settings. Here, we report a case that was positive for HPV73 and 33 and negative for other common subtypes. This case highlights that caution should be taken in cases that are negative for common HPV subtypes but have typical clinical manifestations. That the detection of other subtypes and tissue biopsy should not be ignored.

Vulvar neuroendocrine carcinoma that is independent of merkel cell polyomavirus and human papillomavirus suggests endometrial cancer recurrence: a case report

BackgroundVulvar neuroendocrine carcinomas with small cell morphology need an appropriate differential diagnosis with respect to primary Merkel cell carcinomas, primary small cell neuroendocrine carcinomas, and secondary/metastatic carcinomas. Herein, we report a woman with a history of endometrial carcinoma led to neuroendocrine vulvar carcinoma.Case presentationAn 82-y-old woman with right vulvar swelling was transferred to our hospital. Computed tomography scan showed a 75 mm irregular mass in her right vulva. Three years ago, she had been diagnosed with endometrial endometrioid carcinoma stage IA and had undergone surgery. Vulvar biopsy revealed neuroendocrine carcinomas with small cell morphology. Immunohistochemical staining showed that the vulvar tumor was positive for CD56 and chromogranin A, but negative for Merkel cell polyomavirus and cytokeratin 20. Incidentally, her endometrial carcinoma was also positive for CD56 and chromogranin A. Human papillomavirus DNA typing analysis of vulvar tumor was negative. Hence, the vulvar tumor seemed to be a recurrence of the endometrial cancer rather than a primary vulvar neuroendocrine carcinoma. The patient died of the disease within a month.ConclusionWe report a case of vulvar neuroendocrine carcinoma that is independent of Merkel cell polyomavirus and human papillomavirus, thereby suggesting a recurrence of endometrial cancer. Immunohistochemical and virological analyses helped in the differential diagnosis of the neuroendocrine carcinoma.

Cutaneous β HPVs, Sun Exposure, and Risk of Squamous and Basal Cell Skin Cancers in Australia.

Sun exposure causes cutaneous squamous (SCC) and basal cell (BCC) carcinomas. Human papillomavirus (HPV) infection might cause SCC. We examined associations of β and γ HPV infection in skin-swab DNA and serum antibodies with skin cancer risk, and modification of the carcinogenic effects of sun exposure by them, in case-control studies of 385 SCC cases, 832 BCC cases, and 1,100 controls nested in an Australian prospective cohort study (enrolled 2006-2009). Presence of β-1 and β-3 HPV DNA appeared to increase risks for SCC and BCC by 30% to 40% (P adjusted <0.01). BCC was also associated with genus β DNA, OR = 1.48; 95% confidence interval (CI), 1.10 to 2.00 (P adjusted <0.01). Associations were strengthened with each additional positive β HPV DNA type: SCC (OR = 1.07; 95% CI, 1.02-1.12) and BCC (OR = 1.06; 95% CI, 1.03-1.10), Ptrend<0.01. Positivity to genus β or γ in serology, and genus γ in DNA, was not associated with either cancer. There was little evidence that any β HPV type was more strongly associated than others with either cancer. A weaker association of sun exposure with SCC and BCC in the presence of β-3 HPVs than in their absence suggests that β-3 HPVs modify sun exposure's effect. Our substantive findings are at the level of genus β HPV. Like SCC, BCC risk may increase with increasing numbers of β HPV types on skin. The consistency in our findings that HPV infection may moderate the effects of sun exposure, the main environmental cause of SCC and BCC, merits further investigation.

Cervical Precancers and Cancers Attributed to HPV Types by Race and Ethnicity: Implications for Vaccination, Screening, and Management.

Racial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management. Pooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. For all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70). The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types.

Predominance of genomically defined A lineage of HPV16 over D lineage in Indian patients from eastern India with squamous cell carcinoma of the cervix in association with distinct oncogenic phenotypes

Human papillomavirus type-16 (HPV16) is classified into lineages, A, B, C and D and 10 sub-lineages portraying variable infectivity, persistence, and cytological outcomes, however, with geographical variations. Our objective was to delineate the distinctive features of lineages among cervical squamous cell carcinoma (SCC) in the eastern region of India. A total of 145 SCC cases and 24 non-malignant specimens, harboring episomal HPV16, were included. The presence of higher proportion of lineage A over D was observed among SCC cases (86.89% A1, 8.97% D1 and 4.14% D2), while only A1 sub-lineage viruses were found among control specimens. Among the A1 viruses, an association of variants in the E5 (Y44L, I65V), E6 (L83V) genes and LCR: C7577T with SCC, with combined Odd's ratio (95% CI) of 20.5(4.61–91.25) was observed. Network analyses revealed the presence of 10 clades of lineage A viruses comprising of 64 HPV16 genomes harboring the risk alleles. High episomal HPV16 DNA copy numbers (adjusted p-value= 0.0271) and E7 mRNA expression (p-value=0.000017) predominated in SCC with lineage A, over D. Our study highlights the distinctive modalities of oncogenicity among different HPV16 lineages.

Prevalence and Genotype Distribution of Human Papillomavirus Infection among 12 076 Iranian Women

Introduction: Human papillomavirus (HPV) infection is one of the major health concerns of women in developing countries. This study gives an insight into the prevalence and genotype distribution of HPV infection and compares it with Pap smear results among Iranian women.Methods: In this study, 12 076 Iranian women underwent routine examination from November 2016 to November 2018 using HPV Direct Flow CHIP System for HPV DNA typing. Cytology was undertaken for 5138 samples.Results: Overall HPV prevalence was calculated at 38.68%. The most frequent HPV types were HPV 6, 16, 11, 62/81, 52 and 54. The most high-risk HPV (HR-HPV) types were HPV 16, 52, 18, 39, 31 and 51. These 2 groups represent approximately half of all HPV types detected, 47% and 55%, respectively. Among individuals who underwent cytological tests, 135 individuals (2.63%) were cytologically positive. In this group, 81 individuals (60%) were HPV positive, 62 (76%) of whom were HR-HPV positive, most frequently with HPV 16 (34%).Conclusion: This study highlights the urgent need for public education and early diagnosis using HPV screening tests to prevent cervical cancer.

Correlation of the ALA-PDT Treatment Efficacy and the HPV Genotype Profile of Genital Warts after Cryotherapy Failure and Podophyllotoxin Therapy in Male Patients.

Background: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. Methods: Twenty-one male patients (age range: 22–58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. Results: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types—76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. Conclusion: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation.

Diagnostic Efficacy of DNA Ploidy in Liquid Based Cervical Cytology using DNA Cytometry

Worldwide cervical cancer is the fourth most common cancer in women and high incidence is reported from India. Liquid Based Cytology (LBC) provides good morphology for detection of cellular abnormalities. We, therefore, reviewed diagnostic efficacy of conventional Pap staining, flow cytometry and Human Papilloma Virus (HPV) testing in cervical pre cancer and cancer. Narrative review of cervical pre cancer and cancer candidate biomarkers including Pap staining, HPV and flow cytometry from cervical cytology fluids, is based on a detailed review of the literature. Based on the so far conducted studies, a promising conclusion can be drawn, that cytometry when coupled with HPV DNA typing or the conventional cytology gives better results as compared to that of conventional cytology or DNA cytometry alone. Liquid cytology provides a good and stable source of cervical cells to carry out ploidy studies using DNA cytometry. The procedure should be used in conjunction with LBC and HPV detection.

Association of oral HPV16 infection with periodontal inflammation and the oral microbiome in older women.

The present preliminary study aimed to investigate the association between oral human papillomavirus type 16 (HPV16) DNA prevalence and periodontal inflammation in older women. The association between oral HPV16 infection and oral health status has not been fully elucidated in older Japanese women. The present study investigated older women aged ≥60 years who visited Hiroshima University Hospital. The present study excluded subjects with clinical factors affecting HPV infection, such as current smoking, oral cancer and pre-malignant lesions, and immunodeficiency. Finally, 46 female patients (mean age, 74.6 years) were analyzed. Quantitative PCR analysis was performed to detect HPV16 DNA in oral rinse samples. A total of 4 participants (8.7%) were HPV16 DNA positive. There was a significant association between the HPV16 DNA positivity rate and bleeding on probing (P=0.03). Additionally, Prevotella intermedia positive cases exhibited a significantly higher HPV16 DNA positivity rate than negative cases (33.3 vs 3.8%). Furthermore, analysis of 16S ribosomal RNA in bacterial flora was performed to examine microbiome diversity in participants with ≥6 mm periodontal pockets and bleeding on probing. Importantly, the average percentage of Porphyromonas was significantly higher in HPV16 DNA positive cases compared with in HPV16 DNA negative cases (5.57 vs. 1.44%). By contrast, the average percentage of Veillonella was significantly lower in HPV16 DNA positive cases than in HPV16 DNA negative cases (2.43 vs. 8.51%). Prevotella was also lower in HPV16 DNA positive cases than in HPV16 DNA negative cases (4.0 vs. 8.23%). These results indicated that people with both deep periodontal pocket inflammation and oral HPV16 infection may not have Prevotella- or Veillonella-dominant oral microbiomes, and their microbiomes may exhibit their own distinctive characteristics. In conclusion, the results suggested that oral HPV16 infection may be associated with periodontal inflammation in older Japanese women. Further research is required to clarify the detailed association between oral HPV infection and the oral microbiome.

Circulating tumor HPV DNA complements PET-CT in guiding management after radiotherapy in HPV-related squamous cell carcinoma of the head and neck.

Positron emission tomography and computed tomography (PET-CT) is widely used to assess the response to radiotherapy. However, the ability of PET-CT to predict treatment failure in human papillomavirus (HPV)-related squamous cell carcinoma of the head and neck (HNSCC) is unsatisfactory. We quantified circulating tumor HPV type16 DNA (ctHPV16DNA) using optimized droplet digital PCR in 35 patients with HPV16-related HNSCC, who received radiotherapy with or without chemotherapy, and prospectively correlated ctHPV16DNA and metabolic response with treatment failure. After a median follow-up of 21 months, ctHPV16DNA and PET-CT had similar negative predictive values (89.7% vs 84.0%), whereas the positive predictive value was much higher in ctHPV16DNA than in PET-CT (100% vs 50.0%). Notably, six patients who had detectable posttreatment ctHPV16DNA all had treatment failure irrespective of metabolic response, whereas none of five patients who had partial metabolic response without detectable posttreatment ctHPV16DNA had treatment failure. The risk of treatment failure was high in patients who had incomplete metabolic response with detectable posttreatment ctHPV16DNA (hazard ratio [HR], 138.8; 95% confidence interval [CI], 15.5-3366.4; P < .0001) and intermediate in patients who had discordant results between metabolic response and posttreatment ctHPV16DNA (HR, 4.7; 95% CI, 0.8-36.2, P = .09) as compared with patients who had complete metabolic response without detectable posttreatment ctHPV16DNA. One-year event-free survival rates of each risk group were 0%, 88% (95% CI, 46-98) and 95% (95% CI, 72-99), respectively (P < .0001). In conclusion, posttreatment ctHPV16DNA complements PET-CT and helps guide decisions managing patients with HPV16-related HNSCC after radiotherapy.

Detection of HPV16 E6 DNA in periodontal pockets of middle‐aged and older people

AbstractBackgroundThis study was conducted to investigate the association between oral human papillomavirus type 16 (HPV16) DNA prevalence and periodontitis.Materials and MethodsWe analyzed 89 patients (mean age 71.9 years, range 48‐90 years) who visited the Department of Oral Health of Hiroshima University Hospital. Samples were collected by inserting sterilized paper points into each patient's deepest periodontal pocket to obtain gingival crevicular fluid. Real‐time PCR was performed using type‐specific primers to detect HPV16 DNA. PCR‐targeted bacterial 16S rRNA genes were used to detect periodontal disease‐related bacteria.ResultsOf the 89 participants, four women (4.5%) were HPV16 DNA‐positive. Three of the four HPV16 DNA‐positive participants (75.0%) exhibited bleeding after the paper point was inserted, indicating periodontal tissue inflammation. However, no significant association was found between bleeding and the HPV16 DNA‐positive rate. Importantly, HPV16 DNA positivity was significantly associated with Treponema denticola and Fusobacterium nucleatum (P = 0.01 and P = 0.02, respectively).ConclusionsHuman papilloma virus localizes in periodontal pockets. Inflamed periodontal pockets may indicate oral HPV infection. Periodontitis‐related bacteria may be involved in HPV infection of the periodontal tissues.

Prevalent and persistent oncogenic HPV types in a cohort of women living with HIV prior to HPV vaccination.

To describe prevalent and persistent oncogenic human papillomavirus (HPV) types detected in women living with HIV (WLWH) in Canada, including women with cervical dyskaryosis, and to determine predictors of type-specific HPV persistence. Women and girls living with HIV, recruited from 14 sites of HIV care across Canada, were included in a sub-analysis of a prospective vaccine immunogenicity cohort study (two HPV DNA results, at least one cervical cytology result pre-vaccination). Demographic and clinical data were collected alongside cervical samples for cytology and HPV DNA typing between November 25, 2008, and May 19, 2015. Pre-vaccination, HPV16 and HPV52 were the most prevalent oncogenic HPV types. Of the 252 women and girls who met the eligibility criteria, 45% were infected with at least one oncogenic HPV type and one-third of participants had a persistent oncogenic infection. HPV16, 45, and 52 were the most frequently persistent types. Seventeen percent of women had persistent infections with oncogenic HPV types not within currently available vaccines (HPV35/39/51/56/59/68/82). Lower CD4 count significantly predicted HPV persistence (P=0.024). Cervical cytology results were normal for 82.9% of participants, atypical squamous cells of undetermined significance for 2.4%, low-grade squamous intraepithelial lesions for 11.5%, and high-grade squamous intraepithelial lesions for 2.8%. Unvaccinated WLWH were infected with a wide range of oncogenic HPV types. The findings highlighted the importance of optimal treatment of HIV and continued cervical cancer screening as key steps toward the global elimination of cervical cancer.