Negative Human Papillomavirus Research Articles

Unveiling Hidden Risks: Intentional Molecular Screening for Sexually Transmitted Infections and Vaginosis Pathogens in Patients Who Have Been Exclusively Tested for Human Papillomavirus Genotyping.

This analytical, prospective, cross-sectional study included 408 males and females. Eligible participants had positive and negative HPV genotyping test results and agreed to early detection or had HPV antecedents. They provided the same urogenital samples used for HPV detection and, through our multiplex in-house PCR assay, we screened for Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2 (HSV), Mycoplasma spp., molluscum contagiosum virus (MCV), Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. The subsequent statistical analysis aimed to reveal correlations between HPV genotypes and the identified pathogens. Of the participants, 72.1% (n = 294) tested positive for HPV genotypes. HR-HPV (high-risk HPV) genotypes comprised 51 (8.1%), 66 (7.1%), and 58 (6.1%). Haemophilus spp., Ureaplasma spp., Candida spp., Staphylococcus aureus, and Mycoplasma spp. frequently co-occurred with HPV infection (p < 0.05). Gender-based variations were notorious for Ureaplasma spp., Mycoplasma spp., and MCV (p < 0.05). Coinfections were prevalent (43.9%), with a positive HPV result elevating the risk for Trichomonas vaginalis, Mycoplasma spp., Staphylococcus aureus, HSV, and MCV (OR > 1, p < 0.05). HPV 16 correlated with HSV and Ureaplasma spp., while HPV 6 was linked with HSV and MCV (p < 0.05). This screening strategy uncovered significant coinfections and associations between HPV genotypes and pathogens, underscoring the importance of routine screening to explore clinical implications in urogenital health.

The Role of Human Papilloma Virus in the Pathogenesis of Sinonasal Inverted Papilloma; A Metanalytical Study

Abstract Background Sinonasal inverted papilloma (SNIP) is a benign and relatively rare tumor of the nasal cavity and paranasal sinuses, most commonly originates from the lateral nasal wall or maxillary sinus from the schneiderian sinonasal epithelium. There is a male predominance with a male-to-female ratio of 3.4:1. Sinonasal Squamous Cell Carcinoma (SCC) associated with IP has an incidence of approx. 0.38 cases/million persons/year. Patients with carcinoma in IP are older than those IP patients without carcinoma. Some authors assume an influence of Human Papilloma Virus (HPV) subtyping. Transcripts of HPV DNA were found in malignant IP. Objective To perform a meta-analytical study to determine the relationship between human papilloma virus and the occurrence of sinonasal inverted papilloma. Patients and Methods The review will be restricted to RCTs, clinical trials, and comparative studies, either prospective or retrospective, which studied the outcome of Negative HPV group versus Positive HPV group of patients. Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2021. Data Extraction If the studies did not fulfill the inclusion criteria, they were excluded. Study quality assessment included whether ethical approval was gained, eligibility criteria specified, appropriate controls, and adequate information and defined assessment measures. Results In our study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). HPV positive cases among malignant SNIP patients was (51.02%) (25/49). Conclusion In this meta-analytical study HPV positive cases were (23.6%) (107/ 452) among SNIP patients. Malignant SNIP rate was (10.8%) (49/ 452). Though the etiology of SNIP remains controversial, the studies reviewed in this study indicate a role for HPV infection. Further studies in the future regarding the impact of other risk factors on the occurrence of SNIP would be of value, these factors include angiogenic factors, environmental factors, genetic, viral and chronic sinonasal inflammation.

P16INK4a and pRb expression in laryngeal squamous cell carcinoma with and without infection by EBV or different genotypes of HPV: a retrospective study

BackgroundLaryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein–Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC.MethodsTumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry.ResultsOf the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05).ConclusionOur results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC.

Programmed death-ligand 1 and p53 as a biomarker in predicting oropharyngeal squamous cell carcinoma

Introduction. Currently, the pathogenetic role of the human papillomavirus (HPV) in carcinogenesis is well studied, that most cases of oropharyngeal squamous cell carcinoma are associated with the persistence of this infection. In addition to HPV infection, the involvement of programmed death-ligand 1 (PD-L1) and p53 proteins in the initiation and progression of oropharyngeal squamous cell carcinoma provides their formation as additional biomarkers in predicting the disease.Aim. To study the prognostic role of PD-L1 and p53 expression in oropharyngeal squamous cell carcinoma depending on HPV status.Materials and methods. The study included 62 patients with oropharyngeal squamous cell carcinoma T1–4N0–3M0 (Tumor, Nodus and Metastasis, (TNM), 7th edition) treated in 2015–2020 at the Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology and in the Tashkent and Samarkand city branches. All patients underwent immunohistochemical analysis for the presence of p16INK4a, PD-L1 and p53 protein expression in formalin-fixed and paraffin-embedded tumor tissue samples.Results. Based on the results of the assessment, it was found that positive HPV status, low and medium levels of PD-L1 expression and positive regulation of wild-type p53 are associated with favorable outcomes in patients with oropharyngeal squamous cell carcinoma. Negative HPV status, high and very high levels of PD-L1 expression, loss of wild type p53 function with upregulation of p53 mutant type leads to worse disease outcomes.Conclusion. Thus, the assessment of the expression of the onco-suppressor protein p53 helps to determine the biology of cancer cells in patients with oropharyngeal squamous cell carcinoma and suggest sensitivity to ongoing therapy, and by studying the regulation of the PD-L1 protein, antitumor immune regulation can be suggested in these patients.

Risk of decreased ovarian reserve in women with HPV infection and cervical lesions.

Human papillomavirus (HPV) infection has been considered an important involved factor for infertility. Since one of the causes of decreased ovarian reserve is oophoritis due to viral infections, this study aimed to evaluated the association between HPV infection and ovarian reserve. This case-control study was performed on 219 women aged 25-35 years who were referred to the gynecologic oncology clinic during 2019-2020. The positive or negative HPV infection was confirmed by cervical biopsy and polymerase chain reaction (PCR) test. Cervical lesions or abnormalities in the cervix were assessed by colposcopy and histopathological analysis. Serum anti-Mullerian hormone (AMH) levels were measured for all participants to assess ovarian reserve. The results of this study showed that in patients who were HPV positive, decreased ovarian reserve was more common than in the HPV negative group (p = 0.0001). Also, there was a significant difference between Cervical intraepithelial neoplasia (CIN) I and CIN III sub-groups in AMH level (p = 0.0001). Traces of HPV have been observed in various aspects of infertility, but no study has been performed on its association with ovarian reserve. According to the results of this study, decreased ovarian reserve was more common in patients who were HPV positive.

Association of pretreatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

6052 Background: Lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer (HNC) was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of pre-radiation LMR with survival outcomes in North American patients with HNC. Methods: A single-institution database was queried for patients with non-metastatic HNC who underwent curative-intent definitive chemoradiation from 6/2007 to 4/2021 at the Roswell Park Comprehensive Cancer Center. Patients were excluded if they underwent induction chemotherapy or postoperative radiation. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS), Cox multivariable analysis (MVA), and Kaplan-Meier method. LMR was stratified into high and low based on its median. Logistic MVA was performed to identify variables associated with low LMR. Propensity scored matching was used to reduce selection bias. Subgroup analyses were performed among those with available human papillomavirus (HPV) status. Results: A total of 476 patients (391 male [82.1%], median [interquartile range] age, 61 [55-67] years) met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model using RCS showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau and crossed the hazard ratio of 1 at LMR 3.4 for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.82-1.00, p = 0.04) and CSS (aHR 0.81, 95% CI 0.70-0.94, p = 0.005). The median value of LMR was 3.8. On logistic MVA, patients with other racial background (adjusted odds ratio [aOR] 0.85, 95% CI 0.74-0.97, p = 0.02) and positive HPV status (aOR 0.82, 95% CI 0.72-0.94, p = 0.005) were less likely to have low LMR. Higher T staging was associated with low LMR (aOR 1.15, 95% CI 1.04-1.27, p = 0.005). A total of 186 pairs were matched with well balanced baseline characteristics. LMR lower than 3.8 remained associated with worse OS (HR 1.60, 95% CI 1.13-2.28, p = 0.009) and CSS (HR 1.69, 95% CI 1.07-2.67, p = 0.03). In the subgroup of 319 patients (67.0%) with available HPV data, LMR status was not associated with both OS and CSS regardless of HPV status. Conclusions: Low LMR was associated with worse OS and CSS. Low LMR was also associated with higher T staging, negative HPV status, and White race. Further studies are warranted to evaluate the role of such prognostic marker to tailor interventions.

Significant outcomes associated with high-risk human papillomavirus negative Papanicolaou tests.

The 2020 American Cancer Society guidelines preferred primary human papillomavirus (HPV) screening for cervical cancer prevention. Studies investigating the role of cytology in detection of cervical precancer/cancer have focused on high-grade squamous intraepithelial lesion (HSIL) or worse interpretations. Here, we have examined the significance of all those cytology results that require histologic follow-up as per the current management guidelines, regardless of the HPV test result. A database search (September 2010 to December 2019) retrieved cervical Papanicolaou tests with any of the following interpretations: ≥ atypical squamous cells - cannot exclude HSIL or low-grade squamous intraepithelial lesion, HSIL cannot be excluded, and ≥ atypical glandular cells, not otherwise specified and its subcategories. Of these, those with concurrent negative HPV test result were included for further analysis. For this cohort, relevant clinical history and histologic follow-up (within 1year) were recorded. The study cohort comprised 763 patients. Of them, 586 (76.8%) patients had histologic follow-up: 53 (9.0%) had ≥ HSIL/adenocarcinoma in situ; of which, 43 (81.1%) had prior abnormal cytology/histology/not otherwise specified history and/or HPV positivity, and 66 (11.3%) had HPV-unassociated neoplasia; of which, 60 (90.9%) had a known diagnosis or clinical signs/symptoms of the disease. With widespread adoption of risk-based approach to management, the role of cytology, by itself, will likely diminish in the detection of HPV-associated lesions. Additional data regarding the role of cytology in the screening of patients with no/unknown/limited history and in the detection/management of HPV-independent lesions may be helpful for designing future screening guidelines.

HPV Cotesting of Unsatisfactory Papanicolaou Tests: Implications for Follow-up Intervals.

The 2019 American Society of Colposcopy and Cervical Pathology management guidelines recommend that patients with an unsatisfactory Papanicolaou (Pap) test (UPT) and negative human papillomavirus (HPV) cotest undergo repeat age-based screening in 2 to 4 months. The rationale is that a negative HPV test in the setting of an UPT may reflect an inadequate sample and therefore should not be interpreted as truly "negative." For patients 25 years and older who are cotested, if HPV is positive for the 16 or 18 genotypes, direct referral for colposcopy is recommended. Our study aimed to determine if a negative HPV cotest result is predictive of the absence of a high-grade squamous intraepithelial lesion (HSIL) and whether these patients may be called back for repeat testing at an interval longer than 2 to 4 months. Follow-up cervical cytology and biopsy results in women with UPT and HPV cotests from January 2017 to December 2021 were collected. Original UPT and HPV cotest results were correlated with the follow-up Pap and biopsy results. There were 1,496 (2.28%) UPT cases out of 65,641 total Pap tests. Among the 1,496 UPT cases, 1,010 (67.5%) had HPV cotesting; 676 (45.1%) were followed by repeat Pap or biopsy within 4 months and 850 (56.8%) within 12 months. The total follow-up rate was 81%, with a range of 3 days to 36 months. The HSIL rate in HPV-positive cases was 5.7% (3/53) vs 0.4% (2/539) (P = .006) in HPV-negative cases. In UPT, HPV cotesting showed negative predictive values for low-grade and high-grade squamous intraepithelial lesion detection of 98.5% and 99.6%, respectively, while positive predictive values were 19% and 5.7%. A negative HPV cotest in individuals with UPT predicted the lack of HSIL in our study. Compliance with the recommended follow-up time of 2 to 4 months for women with UPT was low (45.1%). Our study suggests that women with UPT and negative HPV cotest may be safely called back at an interval longer than 4 months.

Expression signature and molecular basis of CDH11 in OSCC detected by a combination of multiple methods

Oral squamous cell carcinoma (OSCC) is one of the most common malignancy in the oral cancer threatening human health and the survival rate of OSCC has not been effectively improved in recent decades, so more effective biomarkers for the targeted therapy of OSCC are needed. Moreover, the role of CDH11 in OSCC has not been intensively investigated. We here show that the CDH11 protein and mRNA expression levels in the OSCC tissues were all significantly higher than in the non-cancerous tissues using RT-qPCR and western blot. This study also revealed that patients with higher CDH11 levels showed a higher incidence of perineural invasion and lymph node metastasis. By using data available from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases, overexpressed CDH11 in OSCC that associated with patients’history of alcohol, negative Human Papilloma Virus (HPV) status, perineural invasion, infiltration of multiple immune cells, and Single-cell functional states including quiescence and angiogenesis, possessed an excellent discriminatory capability in the OSCC patients. Moreover, the majority of the biological processes or pathways were significantly clustered by co-expressed genes, including extracellular matrix organization, the epithelial to mesenchymal transition, carbon metabolism, and the PI3K-Akt signaling pathway, and the upstream transcriptional regulation mechanism of CDH11 in OSCC was showed on a transcription factor/miRNA-mRNA network with the online tool NetworkAnalyst. Finally, frequent mutation of CDH11 was observed on a mouse OSCC model through whole-genome sequencing. CDH11 might serve as a valuable biomarker in OSCC, as it was identified to be overexpressed in OSCC and related to its clinical progression.

Evaluation of anal cytology and human papillomavirus infection in high-risk women: a cross-sectional study

BACKGROUND Anal cancer incidence has been on the rise over the past few decades. This study aimed to assess anal Papanicolaou (Pap) smear changes in women with high risk for dysplasia and human papillomavirus (HPV) infection.&#x0D; METHODS This cross-sectional study was conducted on 121 patients referred to the Gynecology Oncology Clinic of Imam Hossein Medical Center between 2020 and 2021 in Tehran, Iran, who had cervical and vulvar dysplasia, cervical HPV infection, and abnormal cervical cytology results and were over 21 years old. Data analysis was performed using SPSS software version 21 (IBM Corp., USA) at a significance level of 0.05.&#x0D; RESULTS 121 women, with a mean age of 39.69 years, were included in this study. Overall, 23.1% of women had positive anal HPV results, and 35.5% were over 40 years old. Younger age was associated with an increased risk of anal HPV (p = 0.045). 33.9% of women were single and had a higher risk of anal HPV. Multiple sexual partnerships and anal sex were the significant risk factors for anal cancer (p&lt;0.001). Women with positive anal HPV results had significantly more genital warts (p&lt;0.001). No significant difference was observed in smoking, educational level, and cervical Pap smear results between women with negative and positive rectal HPV results.&#x0D; CONCLUSIONS Younger age at diagnosis, being single, having multiple sexual partnerships, having anal sex, and having genital warts were associated with anal HPV infection in women. Abnormal anal cytology was only associated with being single and having multiple sexual partners.

Association Between E6 and E7 Human Papilloma Virus Type 16 Oncogen Mutations and P21 Protein Expression in Cervical Cancer

Cervical cancer is a disease characterized by the growth of abnormal cells in the cervical tissue. Cervical cancer is mostly caused by Human Papillomavirus (HPV) types 16 and 18. The role of genetic factors in the development of cervical malignancy is mediated by the presence of a mutation in the HPV 16 oncogene, especially oncogenes E6 and E7. Oncogenic proteins E6 and E7 in HPV initiate dysregulation of cellular proliferation and apoptotic mechanisms by targeting tumor suppressor proteins, such as the p21 protein. The purpose of this study was to assess the association between mutations in the E6 and E7 oncogenes of HPV-HR Type 16 and the pattern of p21 protein expression. This cross-sectional study was conducted at the Obstetrics and Gynecology Polyclinic of Prof. Dr. I.G.N.G. Ngoerah Hospital, from September 2020 to September 2021. The material taken was cervical cancer tissue from cervical cancer patients and then put into a preservative solution and then put in a cooler. DNA isolation was performed, and PCR was performed to determine positive and negative HPV. The amplification of the E6 and E7 genes was carried out before the sequencing and analysis of the E6 and E7 gene mutations was carried out. Then, immunohistochemical staining of p21 was carried out, followed by data analysis using SPSS for windows version 22.0. There were no significant differences in characteristics between the two groups. There was no association between mutations in the E6 and E7 HPV Type 16 oncogenes with p21 protein expression in cervical cancer cases (p-value 0.22).

Prevalence of higher-grade dysplasia in persistently high-risk human papillomavirus positive, cytology negative women after introduction of the new cervical cancer screening in Germany

PurposeAccording to the recently implemented organized cervical cancer screening program in Germany, women older than 35 years with negative cytology but persistent high-risk human papilloma virus (hrHPV) infection > 12 months should be referred to colposcopy for further evaluation. This study aimed to present and dissect colposcopic and histopathological findings with particular focus on associated hrHPV genotypes.MethodsThis study is a retrospective analysis of clinical data from 89 hrHPV positive patients with normal cytology who underwent colposcopic examination at a certified dysplasia outpatient clinic in Germany in 2021.ResultsWhile 38 (43%) women had a normal colposcopic finding, 45 (51%) had minor and 6 (7%) major changes. Thirty-one (35%) of the women were HPV 16 and/or HPV 18 positive and 58 (65%) women were positive for other hrHPV only. Among patients who underwent colposcopy with biopsies (in case of an abnormal finding or type 3 transformation zone, n = 68), eight (12%) had cervical intraepithelial neoplasia (CIN) 3 and six (9%) had CIN 2. The proportion of women diagnosed with CIN 3 varied among different hrHPV genotypes (HPV 16: 11%, HPV 18: 33%, HPV 31: 27%, HPV 33: 33%, HPV 52: 33%).ConclusionPersistently hrHPV positive women with negative cytology are at increased risk of being diagnosed with CIN 3. As CIN 3 prevalence seems to differ with regard to hrHPV strain, immediate HPV genotyping for risk stratification and subsequent early referral for colposcopy might constitute a feasible strategy.

Oral health in HPV-positive and HPV-negative patients with oropharyngeal squamous cell carcinoma.

This study compared oral health in oropharyngeal squamous cell carcinoma (OPSCC) patients with positive or negative human papillomavirus (HPV) status and analysed whether oral health was associated with survival. Patients referred for dental assessment prior to radio(chemo)therapy between 2009 and 2019 were included. Patient-related risk factors for OPSCC (alcohol, tobacco, HPV status), age, sex, treatment (primary treatment, intent), performance status, tumor/node/metastasis (TNM) staging, and oral health parameters (DMFT, periodontal status, teeth with/without root canal treatment and with/without periodontitis apicalis) were compared between HPV-negative and HPV-positive patients. Survival was assessed using Kaplan-Meier statistics. The effect of patient-related risk factors and oral health parameters was analysed by cox regression analyses (α=5%). A total of 119 patients (n=50 HPV-negative, n=69 HPV-positive) was included. HPV-positive patients showed more present teeth, a higher number of filled teeth, were less often edentulous and presented a lower DMFT compared to HPV-negative patients (padj.≤0.003). Among dentulous patients, HPV-positive patients showed more present teeth and fewer teeth with periodontitis apicalis lacking a root canal treatment (padj.≤0.036). Survival probability differed between groups (p=0.006) and trended towards being associated with HPV status, tobacco exposure, performance status, T stage, N stage, and the number of missing or filled teeth as well as the number of root canal treated teeth with periodontitis apicalis and the number of teeth with periodontitis apicalis lacking a root canal treatment (p≤0.077). However, only tobacco exposure, performance status, and the number of teeth with periodontitis apicalis lacking a root canal treatment in dentulous patients remained significant in the multivariate analyses (p≤0.047). HPV-negative patients with OPSCC showed a poorer oral health compared to HPV-positive patients, but survival was not associated with oral health.

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.

Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Three-dimensional wavelet decomposition-based radiomics analysis for tumor characterization in patients with oropharyngeal squamous cell carcinoma

Background: We investigated the potential predictive value along with interpretability of the three-dimensional wavelet decomposition (3D-WD)-based radiomics analysis for characterization of gross-tumor-volumes (GTVs) for patients with Human Papilloma Virus (HPV) oropharyngeal squamous cell carcinoma (OPSCC). The goal was to characterize and identify the spatial frequencies and regions of primary tumor that are responsible for classifying the HPV status. Methods: One-hundred twenty-eight OPSCC patients (60-HPV+ and 68-HPV-, confirmed by immunohistochemistry-P16-Protein) were retrospectively studied. 3D-WD analysis was performed on the contrast-enhanced-CT images of patients’ primary tumor-GTVs to decompose information into three decomposition levels explained by a series of high-pass and low-pass wavelet coefficients (WCs). Log-Energy-Entropy of the WCs was calculated as radiomics features. A Least-Absolute-Shrinkage-and-Selection-Operation (Lasso) technique combined with a Generalized-Linear-Model (Lasso-GLM) was applied on the feature space to identify and rank the frequency sub-bands associated with the HPV status. The classifier was validated using a nested-cross-validation technique. Average of Area Under ROC (AUC), and Positive and Negative Predictive values (PPV and NPV) were computed to estimate the generalization-error and performance of the classifier. The significant features were used to weight tumor sub-band frequencies to reconstruct the tumor zones with highest information towards characterization of HPV. Results: Among 22 frequency-based features, two low-frequency and two high-frequency features were statistically discriminant between the two cohorts. Results (AUC/PPV/NPV=0.798/0.745/0.823) imply that tumor’s high-frequency and low-frequency components are associated with its HPV positivity and negativity, respectively. Conclusions: This study suggests that compared to the central zones of tumor, peritumoral regions contain more information for characterization of the HPV-status. Albeit subject to confirmation in a larger cohort, this pilot study presents encouraging results in support of the role of frequency-based radiomics analysis towards characterization of tumor microenvironment in patients with OPSCC. By associating this information with tumor pathology, one can potentially link radiomics to underlying biological mechanisms.

Patterns and risk factors of recurrence in low-risk early-stage cervical adenocarcinoma treated with surgery alone: implications on risk group stratification

ObjectiveCervical adenocarcinoma has poorer outcomes compared with squamous cell carcinoma; however, treatment is identical irrespective of histologic sub-types. This study aimed to investigate the patterns and risk factors of recurrence...

Development of an Algorithm for Cervical High-Grade Squamous Intraepithelial Lesion Based on Breath Print Analysis.

This study was designed to develop an algorithm for the diagnosis of cervical high-grade squamous intraepithelial lesions (HSIL), based on patterns of volatile organic compounds, evaluated using an e-nose. For this pilot study, the study population consisted of a group of 25 patients with histologically confirmed HSIL and a group of 26 controls. Controls consisted of women visiting the outpatient department for gynecological complaints unrelated to cancer. Women had a negative high-risk human papillomavirus and/or normal cytology (negative for intraepithelial lesions of malignancy) of their most recent test performed in the context of participation in routine cervical cancer screening. Breath tests were performed and labeled with the correct diagnosis. Machine-learning techniques were used to develop a model for predicting HSIL. Based on the receiver operating characteristics curve, both sensitivity and specificity were calculated. Individual classifications of all patients with HSIL and controls, as calculated by the model, showed a sensitivity of 0.88 (95% CI = 0.68-0.97) and specificity of 0.92 (95% CI = 0.73-0.99). The positive predictive value and the negative predictive value were 0.92 (95% CI = 0.72-0.99) and 0.89 (95% CI = 0.70-0.97), respectively. The Cohen κ coefficient was 0.80. E-nose can detect distinctive patterns of volatile organic compounds between cervical HSIL patients and controls. Validation of the algorithm in further studies is necessary before possible implementation into daily practice.

Performance of HPV testing, Pap smear and VIA in women attending cervical cancer screening in Kilimanjaro region, Northern Tanzania: a cross-sectional study nested in a cohort

ObjectiveThere is a concern about performance of the screening approaches, where information on the quality of novel and affordable screening approaches that will perform well in remote areas is warranted....

Untold story of human cervical cancers: HPV-negative cervical cancer

Cervical cancer is the fourth most common malignancy in women worldwide. Although infection from human papillomavirus (HPV) has been the leading cause of cervical cancer, HPV-negative cervical cancer accounts for approximately 3-8% of all cases. Previous research studies on cervical cancer have focused on HPV-positive cervical cancer due to its prevalence, resulting in HPV-negative cervical cancer receiving considerably less attention. As a result, HPV-negative cervical cancer is poorly understood. Its etiology remains elusive mainly due to limitations in research methodology such as lack of defined markers and model systems. Moreover, false HPV negativity can arise from inaccurate diagnostic methods, which also hinders the progress of research on HPV-negative cervical cancer. Since HPV-negative cervical cancer is associated with worse clinical features, greater attention is required to understand HPV-negative carcinoma. In this review, we provide a summary of knowledge gaps and current limitations of HPV-negative cervical cancer research based on current clinical statistics. We also discuss future directions for understanding the pathogenesis of HPV-independent cervical cancer.

HPV Test as Test of Cure After Conization for CIN2+: A Nationwide Register-Based Cohort Study.

The purpose of this study was to assess if cytology can be omitted in the follow-up after treatment for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and if human papillomavirus (HPV) test can be used alone as test of cure (TOC) after stratifying for resection margins. In this retrospective register-based study, women who had a conization performed in Denmark between January 1 and December 31, 2013, were included. Histology, cytology, and HPV test results were obtained from The Danish Pathology Data Bank for a 3-year follow-up. A total of 5,174 women were included, of whom 6.1% (318/5,174) had histological residual/recurrent disease in the follow-up period. In the group with free margins, 2.6% (73/2,780) had residual/recurrent disease in contrast to 10.2% (245/2,394) in the group with involved margins. In the group with free resection margins and negative HPV test results, residual/recurrent disease was found in 0.5% (13/2,780) compared with 0.3% (9/2,780) in the group with negative HPV test results and normal cytology at 6 months' follow-up. Based on margin status and HPV test result as follow-up, the sensitivity, specificity, and positive and negative predictive values were 95.9%, 43.2%, 10.0%, and 99.4% respectively, and for combined testing (margin status, HPV, and cytology), 97.2%, 41.2%, 9.8%, and 99.6%, respectively. Using the HPV test at the first post-treatment control as TOC for cervical intraepithelial neoplasia grade 2 or worse after stratifying for resection margins in cone resections yields an equally high sensitivity and negative predictive value as cotesting with cytology. We suggest that women with free resection margins return to the routine screening program after negative HPV test result as TOC at 6 months.