Human Papillomavirus Infection Status Research Articles

Human papillomavirus infection in metastatic lung adenocarcinoma is associated with better outcomes with immune checkpoint inhibitor treatment.

e21569 Background: Human papilloma virus (HPV) is associated with the development of several primary tumors. Recent studies have shown that HPV-positive tumors tend to be sensitive to immune checkpoint inhibitors (ICI), owing to the presence of xenobiotic genomes in cancer cells. The objective of this study was to explore this relationship in patients with lung adenocarcinoma. Methods: A retrospective cohort analysis in patients with advanced lung adenocarcinoma treated in a reference center in Bogota, Colombia was conducted. Demographic as well as treatment variables were collected between January 2018 and December 2019. Besides clinical outcomes, HPV infection status was determined by PCR amplification and reverse line hybridization directly on formalin-fixed paraffin-embedded tumor samples. Statistical analyses included stratified survival analysis based on HPV status and response. Results: A total of 133 patients were included. Male predominance (51.1%) with Karnofsky performance scores (KPS) greater than 80, and 19% of prior cigarette exposure (26 patients) was identified in the cohort. HPV positivity was identified in 25.6% of patients (33 cases, [95%CI 17.5-32.2%]), in addition to 29.8% EGFR mutation positivity (29 cases [[95%CI 14.8-28.8%]), 6% ALK positivity (8 cases [95%CI 1.9-10]) and positive PD-L1 expression in 49 samples (36.8% [95%CI 28.6-45%]). In immune checkpoint inhibitor (ICI) exposed patients, HPV+ patients had significantly higher PD-L1 expression compared with HPV- individuals (p < 0.001). In terms of overall survival, ICI treated patients achieved an OS of 27.1 months (95%CI 22.1-NA) and a PFS of 19.4 months (95%CI 18-24.5 months). HPV infection status was associated with prolonged OS (median OS not reached, [95%CI 27.7 months – no reached], p = 0.0089) and better response to ICI (p < 0.001). Conclusions: HPV infection is prevalent in patients with lung adenocarcinoma and is associated with better response to ICIs as well as better survival outcomes. Its identification could serve as a prognostic marker, especially in female non-smoker patients.

Studying the interrelation between the HPV infection status and the morphological features of bladder cancer.

e17003 Background: The etiological role of human papillomavirus (HPV) in the development of squamous cell carcinoma of the cervix and larynx is considered proven. At the same time, there are conflicting data in the literature on the role of HPV in the development of bladder cancer (BC). The aim of the present study was to evaluate the prevalence of HPV infection in patients with BC, identifying the relationship between the status of infection and the morphological characteristics of the tumor. Methods: The study included 46 patients (10 women and 36 men) with morphologically confirmed urothelial cancer. Samples of urine, tumor tissue and a healthy bladder mucosa were examined. HPV DNA was determined by real-time PCR. Results: 28 (60.9%) patients were infected with high-risk HPV, including 6 (60.0%) women and 22 (61.1%) men. In 14 (30.4%) patients, HPV DNA was found in the tissue of the bladder mucosa: in 6 (13.0%) cases it was only in tumor tissue, in 4 (8.7%) only in healthy mucosa, in 4 (8.7%) simultaneously in healthy and tumor tissue. HPV DNA was detected in urine in 22 (47.8%) patients. The simultaneous presence of HPV DNA in the tissue of the bladder mucosa and urine was found in 8 (28.6%) HPV-positive patients. Single HPV infection was found in 20 (71.4%) patients, two types were found in 8 (28.6%). When analyzing type diversity, it was found that HPV16 infected 14 (38.9%) patients; HPV18, 31, 39 and 56 were determined in 4 (11.1%) cases each; 33, 52 and 59 types in 2 (5.6%) cases. Chronic inflammation was noted in 12 (26.1%) patients, 6 (50.0%) of them were HPV-positive. Among HPV-positive patients, invasive cancer was registered in 18 (64.3%), non-invasive cancer in 10 (35.7%) patients. Among HPV-negative patients, these rates were 14 (77.8%) and 4 (22.2%), respectively (p > 0.05). In the group of HPV-positive patients, tumors with a low degree of differentiation were found in 16 (57.1%), moderate in 6 (21.4%), high in 6 (21.4%). Among HPV-negative patients, these indicators were 4 (22.2%), 12 (66.7%) and 2 (11.1%), respectively (p > 0.05). Conclusions: HPV infection was detected in 60.9% of patients, including tumor tissue infection in 21.7% of patients. The most common HPV type was HPV16. There was no statistically significant difference between HPV-positive and negative tumors.

Dietary Calcium Intake and HPV Infection Status Among American Women: A Secondary Analysis from National Health and Nutrition Examination Survey (NHANES) Data Set of 2003 - 2016.

BackgroundThe evidence on the link of dietary calcium (DCa) to human papillomavirus (HPV) infection is limited. Thus, this research was conducted to explore whether DCa is independently associated with HPV infection status in American women with age of 18 to 59 years old.Material/MethodsWe performed a secondary analysis from the National Health and Nutrition Examination Survey (NHANES) data set including 7 cycles from 2003 to 2016. A total of 13 475 selected participants were used for data analysis. The interested independent and the outcome variable were DCa and HPV infection status (HPV infection; HPV subtype). Sociodemographic, dietary, laboratory, questionnaire, and physical examination data were covariates. Weighted binary logistic regression and generalized additive model (GAM) were used for the investigation of both linear and non-linear relationships between DCa and HPV infection status.ResultsWeighted multivariable binary logistic regression indicated DCa was not associated with HPV infection and subtype (OR: 0.93; 95% CI: 0.82–1.05 for HPV infection; OR: 1.09; 95% CI: 0.93–1.28 for HPV subtype). For HPV infection, a non-linear correlation was detected, whose inflection points were 9.78 of log2 DCa. The OR values and the confidence intervals on both sides of inflection point were 0.83 (95% CI: 0.70–0.98) and 1.18 (95% CI: 0.91–1.52), respectively.ConclusionsAt the range of 3.32–9.78 of log2 calcium intake, DCa intake was negatively correlated with HPV infection. After this interval, DCa intake was not associated with the risk of HPV infection.

Presence of HPV with overexpression of p16INK4a protein and EBV infection in penile cancer-A series of cases from Brazil Amazon.

In Brazil, penile cancer (PC) is not uncommon. The highest incidence of PC is in the North and Northeast of the country. In addition to phimosis, the Human Papillomavirus (HPV) and Epstein-Baar Virus (EBV) infections are also related as risk factors for PC. The overexpression of p16INK4a is a surrogate sensitive marker of HPV infection in PC. To correlate p16INK4a overexpression and HPV infection status with EBV infection in a series of PC patients from the Amazon region. Tumor tissues from 47 PC cases were analyzed for the presence of HPV and EBV DNA by PCR. All PC patients were diagnosed between 2013 and 2018 at a public reference cancer center hospital in Manaus, Amazonas-Brazil. HPV was genotyped using E7 HPV16/HPV18 type-specific real-time PCR and the PapilloCheck® HPV-Screening assay. p16INK4a expression was evaluated by immunohistochemistry using the automated Ventana® BenchMark Ultra. The mean age of patients at the time of diagnosis was 57.4 years ±SD 17.8 ranging from 20 to 90 years old. Most of the patients (64%) came from rural areas of the Amazonas State. Thirty patients had phimosis (64%). Among the patients with phimosis, 43% (13/30) underwent circumcision, three during childhood and 10 in adulthood. 60% of the patients were smokers or ex-smokers. HPV infection was observed in 45% (21/47) of cases. HPV16 was detected in 13 patients (61%). Other HPV types detected were HPV 6, 11, 42, 51, 53, 68 and 44/55. EBV infection was observed in 30% (14/47) of the patients with PC. Co-infection with HPV and EBV was observed in 28% (6/21) cases. p16INK4a was only investigated in 26 samples. The p16INK4a overexpression was observed exclusively in HPV 16 positive cases and four HPV negative cases. In the survival analysis, the follow-up time was 35.4 months/patient. The mortality rate during the follow up time was 38%. p16INK4a positivity presented a high correlation to HPV 16 DNA detection, reinforcing its use as a surrogate marker for HPV-driven cancers. Infection with EBV was quite frequent and its role in epithelial penile oncogenesis needs to be demonstrated.

Prevalence and Prognostic Value of HPV among Tunisian Patients with Laryngeal Cancer and Relationship between DNA HPV and p16, IGF-1R, Survivin, p53 Expressions.

Tobacco and alcohol are the main etiological factors common to laryngeal cancers. However, the Human Papilloma Virus (HPV) constitutes an alternative risk factor according to several studies. In Tunisia, despite the annual increasing incidence of laryngeal squamous cell carcinoma (LSCC), the prevalence and prognostic significance of HPV have never been explored.In this study, we sought to highlight HPV DNA in 70 biopsies of laryngeal cancer, and to analyze the status of HPV infection in association with p53, p16, survivin, and IGF-1R expressions. HPV high risk (HPV HR) DNA was detected in tumors by in situ hybridization. However, the expression of p53, p16, survivin and IGF-1R were stained by immunohistochemistry test. The correlations of HPV status with clinicopathological parameters, overall survival, disease-free survival and proteins expressions were statistically evaluated. HPV HR DNA was detected in 39 out of 70 (55.71%) laryngeal tumors. HPV+ patients have a better overall survival (P = .081) and long disease-free-survival (P = .016) with a low rate of recurrence (P = .006) than HPV- patients. No significant correlations were found between HPV HR status and clinicopathological parameters (all P > .005). Moreover, HPV+ tumors were not associated with expression of p53, p16 and survivin. However, HPV HR status correlates with weak to moderate IGF-1R expression (P = .043). The substantial detection of HPV HR in LSCC tumors suggest that this virus plays an important part in laryngeal cancer in Tunisia. It is a good prognostic factor. In addition, HPV infection could act to block the pathway of IGF-1R expression.

Human Papilloma Virus Infection Status and Oral Cancer Incidence in South India–Lack of Evidence and its Current Impacts

Human Papilloma Virus Infection Status and Oral Cancer Incidence in South India–Lack of Evidence and its Current Impacts

Initial analysis of human papilloma virus for patients with head and neck squamous cell carcinoma in a single center in Chaoshan area of Guangdong Province

Objective To detect the infection and subtype status of human papilloma virus (HPV) for patients with head and neck squamous cell carcinoma (HNSCC) treated in a single center in Chaoshan area of Guangdong Province. Methods The primary lesion samples from 167 HNSCC patients in Cancer Hospital of Shantou University Medical College between December 2014 and December 2016 were collected. The expression of p16 protein in tumor tissues was detected by using immunohistochemistry (IHC), and the positive rate of tumor cell p16 protein≥ 76% was used as a diagnostic standard to judge HPV in HNSCC; the relationship between p16 protein and the clinicopathological factors was analyzed. The status of HPV 16/18 DNA in tumor tissues was tested by using in situ hybridization(ISH). RNA scope was used to detect the RNA expression of 18 kinds of common high-risk HPV subtype (HPV HR 18), and the positive status of HPV HR 18 in tumor tissues with the positive cell proportion ≥ 50% of p16 protein was analyzed. Results The strong expression rate of p16 protein was 7.2% (12/167). The strong expression rate of p16 protein in the younger group ( 0.05). HPV 16/18 DNA was not found in all HNSCC primary lesions by using ISH, which showed the same result after repeated examination. RNAscope method showed that 3 cases (15.8%) out of the 19 patients with p16 protein positive rate≥50% were HPV HR 18 RNA positive. Conclusions The positive rate of HPV for HNSCC patients in Chaoshan area is low, while the patients with oropharyngeal carcinoma have the highest rate and tend to be younger. The main carcinogenic viruses of HPV for HNSCC patients in Chaoshan area are other subtypes of HPV including HPV HR 18 rather than HPV 16/18. Key words: Head and neck neoplasms; Carcinoma, squamous cell; Human papillomavirus; Chaoshan area

Predictive value of p16INK4a, Ki-67 and ProExC immuno-qualitative features in LSIL progression into HSIL.

The current nested case-control study was conducted to explore the prognostic value of cyclin-dependent kinase inhibitor 2A (p16INK4a), marker of proliferation Ki-67 (Ki-67) and immunohistochemical cocktail containing antibodies directed against topoisomerase IIα (TOP2A) and minichromosome maintenance 2 (MCM2) proteins (ProExC) immuno-qualitative features to predict low-grade squamous intraepithelial lesion (LSIL) progression. A total of 92 LSIL patients were followed-up for 2 years, where those with high-grade squamous intraepithelial lesion (HSIL) or persistent LSIL were designated as the case group and those who spontaneously regressed were designated as the control group. The infection status of human papillomavirus (HPV) was evaluated using flow-through hybridization and gene chip, whilst the expression of p16INK4a, Ki-67 and ProExC were tested in LSIL patient biopsies by immunohistochemistry. All data were collected at the beginning of the follow-up and patient outcomes were diagnosed by histopathological examination. To analyze the risk factors for LSIL progression, sensitivity, specificity, positive-negative predictive value (PPV-NPV), positive-negative likelihood ratio (PLR-NLR), Youden's index (YI) and multinomial logistic regression analysis was performed. The expression rates of p16INK4a, Ki-67, and ProExC were found to be higher in the progression group compared with those in the persistence and regression groups. Only p16INK4a expression significantly associated with high-risk HPV infection. With respect to predicting HSIL, p16INK4a staining was the most sensitive but Ki-67 staining was found to be the most specific. YI was the highest (42.1%) for p16INK4a expression in the present study, followed by ProExC (39.5%) and Ki-67 (28.3%). However, the expression of ProExC was found to be an independent risk factor for LSIL progression into HSIL. In conclusion, whilst immunohistochemical staining for p16INK4a, Ki-67, and ProExC can be used to predict HSIL progression, only ProExC expression can be applied an independent risk factor for LSIL progression.

Human papillomavirus infection and p53 mutation in esophageal squamous cell carcinoma and its impact on treatment outcome.

Human papillomavirus (HPV) is emerging as a risk factor for esophageal squamous carcinoma. The prognostic value of the HPV status has been investigated. However, the results are much controversial. This study aims to document the association of HPV infection and mutation of p53 gene in esophageal squamous cell carcinoma (ESCC) and its impact on treatment outcome. The study was conducted over a period of 12 months. A total of 30 cases of ESCC who were primarily to be treated with radiotherapy/chemoradiotherapy were included in the study. All the tissue samples for biopsy were subjected to immunohistochemistry to study p53 and p16 expression, which is a surrogate marker for HPV. The patients were treated by radiotherapy alone or concurrent chemoradiotherapy depending on performance status and stage of disease. The impact of p16 and p53 on overall survival (OS) and disease-free survival (DFS) was determined. The median OS of HPV-positive patients was 22 months (95% confidence interval [CI] 12-31) as compared to 13 months (95% CI 7-18) for HPV-negative patients (P = 0.298). The median DFS for HPV-positive patients was 16 months (95% CI 7-24) as compared to 5 months (95% CI 4-6) for HPV-negative patients (P = 0.048). The median OS of p53-positive patients was 13 months (95% CI 6.7-19) as compared to 22 months (95% CI 12.7-31.2) for p53-negative patients (P = 0.080). The median DFS for p53-positive patients was 5 months (95% CI 3.7-6.2) as compared to 22 months (95% CI 15.7-29.4) for p53-negative patients (P = 0.014). Clinical findings of our result can be used to sum up that both HPV infection and p53 mutation status are reliable biomarkers and can help clinicians to predict treatment outcome and prognosticate patients better.

Low prevalence of human papillomavirus infection in sinonasal inverted papilloma and oncocytic papilloma.

The aim of this study was to investigate the role of human papillomavirus (HPV) in sinonasal inverted papilloma (SIP) and sinonasal oncocytic papilloma (SOP) from a single institution and whether p16 can serve as a surrogate marker for HPV infection. This study included 49 subjects with SIP and 36 subjects with SOP. Formalin-fixed paraffin-embedded tissues were used to extract genomic DNA, and HPV detection was performed by utilizing a valid nested polymerase chain reaction approach that can detect all known HPV subtypes. Immunohistochemistry was used to evaluate the expression of p16 in all tumor sections. The presence of HPV DNA was found in 6.1% (3/49) of the SIP patients and 11.1% (4/36) of the SOP patients. All identified HPV subtypes in SIP were high-risk HPV, including HPV-16 (two patients) and HPV-58 (one patient). Regarding SOP, there were three patients positive for HPV-16 and one with low-risk HPV (type 6). In total, 11/49 (22.4%) SIP lesions and 10/36 (27.8%) SOP lesions were considered p16 positive, with p16 staining in more than 70% of tumor cells. There was only one SIP and one SOP that were positive for both HPV (high-risk HPV type 16) and p16 staining. HPV does not play an etiologic role in inverted papilloma or oncocytic papilloma of the sinonasal region. p16 immunostaining should not be used as a surrogate marker to evaluate the HPV infection status in these lesions.

HPV-related Sinonasal Carcinoma: Clinicopathologic Features, Diagnostic Utility of p16 and Rb Immunohistochemistry, and EGFR Copy Number Alteration.

The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16 SNSCCs were HPV. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV/EGFR CNG group had significantly better overall survival than the HPV/EGFR CNG and HPV/EGFR CNG groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.

Human papillomavirus Posttreatment Clearance Time in Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

ObjectiveThe aim of the study was to determine an appropriate follow-up schedule for human papillomavirus (HPV) detection by evaluating the clearance time of HPV after treatment.Materials and MethodsA retrospective study was conducted on 97 high-grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia 2–3) patients and 437 early invasive cervical cancer (CC) (stages Ia–IIa) patients who received radical surgery at the Affiliated Tumor Hospital of Xinjiang Medical University. Patient medical information, including personal information, pathological diagnosis, HPV infection status, and therapeutic methods, was obtained through the hospital's historical medical records management system. The clearance time of HPV was determined using Kaplan-Meier method analysis, and clearance time of HPV among different age groups, different grades, and different clinical stages were compared using the log-rank test.ResultsThe median clearance time of all patients was 10.4 months. The median clearance time was longer in HSIL patients than in early invasive CC patients (p < .05). No statistical significance was found among different HSIL grades, CC stages, or patient age groups (P > 0.05).ConclusionsDelaying first posttreatment follow-up to 9 months in patients at high risk of noncompliance could potentially reduce burden of cost and repeated clinical visits. This follow-up approach could be consistently applied to all women regardless of age, severity, and extent of disease.

1154P - Expression of estrogen receptor and programmed cell death-ligand 1 can be complementary prognostic factors in HPV-positive oropharyngeal squamous cell carcinoma

BackgroundOropharyngeal squamous cell carcinoma (OPSC) continues to increase in incidence with human papillomavirus (HPV) infection. Despite the good overall prognosis, it needs to assess the risk of not only survival, but also the risk of local, regional, or distant treatment failure to guide de-intensification regimens. This study aimed to investigate the expression of estrogen receptor (ER) and programmed cell death-ligand 1 (PD-L1) proteins according to the status of HPV infection and their prognostic implication in OPSCC patients. MethodsConsecutive 80 patients diagnosed with OPSCC with surgical treatment from 2004 to 2017 were included. Immunohistochemistry for ER and PD-L1 was performed formalin-fixed, paraffin embedded tissues. HPV status assessed with p16 immunohistochemistry and HPV DNA testing. ResultsER and PD-L1 expression were observed in 37.5% (30/80) and 60% (48/80), respectively. Both ER and PD-L1 protein expression were higher in HPV-positive OPSCC than in HPV-negative subgroup (47.5% vs. 9.5% for ER, 66.1% vs. 42.9% for PD-L1). There was no significant association between ER and PD-L1 expression (correlation coefficient: 0.105, p>0.05). Using Kaplan-Meier curves, PD-L1 expression was associated with longer recurrence-free duration (p=0.013), whereas ER expression was associated with prolonged overall survival (p=0.043). In subgroup analysis, PD-L1 expression was found to be an independent excellent prognostic factor for recurrence-free duration in HPV-positive OPSCC (p=0.002, HR=0.085 [0.018-0.399]). ER expression also tended to be associated with longer overall survival in the HPV-positive OPSCC subgroup, but no statistical significance was observed. In HPV-negative subgroup, both ER and PD-L1 expression were not associated with any clinicopathologic factor nor survival. ConclusionsER and PD-L1 expression can be complementary prognostic factors in HPV-positive OPSCC. It may allow us to investigate the independent role of anti-hormone receptors and the tumor microenvironment in the treatment of OPSCC. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

A proposal for classification of oropharyngeal squamous cell carcinoma: Morphology and status of HPV by immunohistochemistry and molecular biology.

The current three-tier grading system (well, moderate and poorly differentiated) used to morphologically classify head and neck squamous cell carcinoma (HNSCC) is inadequate for categorisation of oropharyngeal squamous cell carcinoma (OPSCC) owing to the lack of prognostic value. The aim of this study was to assess the validity of a classification system for OPSCC based on morphology and human papilloma virus (HPV) infection status. Haematoxylin and eosin slides of 121 patients (100 M, 21 F, age range 40-89years) with OPSCC were reviewed and categorised as histological types I, II and III. The presence of HPV was assessed by immunohistochemistry with p16 and RNAscope In situ hybridization (ISH). The follow-up period was 36months. Ninety-six patients were p16+and clinical stage I. Patient survival with types I, II and III was 93%, 50% and 96%, respectively. Twenty-five patients were p16-: 10 clinical stage I and 15 stage III. Amongst this group, no type I morphology was identified. At follow-up, 65% of type II and 75% of type III patients were alive. All p16+cases were also positive for E6/E7 mRNA high-risk HPV by ISH, while 23 p16- cases were negative and two were positive. Cox regression identified three predictors of mortality: older age (HR=1.14, 95% CI=1.06-1.23, P=.001); female gender (HR=0.22.95% CI 0.05-0.88, P=.033); and type II morphology (HR=13.1, 95% CI=1.09-157.0, P=.043). OPSCC morphological classification in three sub-types, along with HPV infection status, seems to reflect the outcome of patients with OPSCC.

Enhancing prognosis prediction using pre-treatment nodal SUVmax and HPV status in cervical squamous cell carcinoma

BackgroundThis study was to evaluate the prognostic value of metabolic parameters on F-18-FDG PET/CT and the status of human papillomavirus (HPV) infection and known prognostic variables for predicting tumor recurrence and investigating a prognostic model in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy (CCRT).MethodsA total of 129 patients with cervical squamous cell carcinoma who underwent initial CCRT were eligible for this study. Univariate and multivariate analyses were performed using traditional prognostic factors, metabolic parameters, and HPV infection. Classification and regression decision tree (CART) was used to establish new classification.ResultsAmong 129 patients, 29 patients (22.5%) had recurrence after a median follow-up of 60 months (range, 3–125 months). Tumor size, para-aortic lymph node metastasis, nodal SUVmax, and HPV infection status were identified as independent prognostic factors by multivariate analysis. The CART analysis classified the patients into three groups. The first node was nodal SUVmax, and HPV status was the second node for patients with nodal SUVmax ≤7.49; Group A (nodal SUVmax ≤7.49 and HPV positive, HR 1.0), Group B (nodal SUVmax ≤7.49 and HPV negative, HR 3.56), and Group C (nodal SUVmax > 7.49, HR 10.13). Disease-free survival was significantly different among the three groups (p < 0.001).ConclusionThe nodal SUVmax on F-18 FDG PET/CT and HPV infection status before CCRT are powerful independent prognostic factors for the prediction of disease-free survival in patients with cervical squamous cell carcinoma who underwent initial CCRT. We also suggest a simple prognosis prediction model using pre-treatment FDG PET/CT and HPV genotyping; however, it needs further validation in an independent dataset.

Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions

Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte–macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.

Human Papillomavirus Genotype Detection in Oral Gargle Samples Among Men With Newly Diagnosed Oropharyngeal Squamous Cell Carcinoma

The most common cause of oropharyngeal squamous cell carcinoma is human papillomavirus (HPV) infection, and currently the standard of care to determine the HPV infection status in this type of carcinoma is to use p16 immunohistochemistry as a surrogate marker of high-risk HPV infection. Although p16 immunohistochemistry is limited by the inability to determine the specific HPV genotypes, oral gargle samples may be a readily available source of HPV DNA for genotyping. To determine the specific HPV genotypes present in both oral gargle samples and tumor specimens. This prospective, biomarker cohort study conducted at a single specialized cancer hospital in Florida screened approximately 800 potentially eligible participants from May 2014 through October 2017. To be eligible for participation, patients had to meet all of the following criteria: 18 years of age or older, male sex, newly diagnosed as having stage I to IV cancer of the oropharynx, a squamous cell carcinoma diagnosis, treatment naive or at least 4 weeks after chemoradiation or surgical treatment of other diseases, fully understand the study procedures and risks involved, and voluntarily agree to participate by signing an informed consent statement. Detection rate of HPV infection and HPV genotypes in oral gargle samples and tumor specimens. A cohort of 204 male participants with newly diagnosed oropharyngeal squamous cell carcinoma was assessed in this prospective collection of comprehensive clinical data and oral gargle samples. Most study participants (190 [93.1%]) were white and ever smokers (114, 55.9%), with a median age of 61 years (range, 35-87 years). The HPV infection status could be assessed in 203 of 204 participants (99.5%) using oral gargle samples: 35 samples (17.2%) were negative for HPV infection, whereas 168 samples (82.8%) were positive for HPV infection. The detection rate of HPV genotypes was 93.0% in tumor specimens (160 specimens) and 82.8% (168 samples) in oral gargle samples. The oral gargle samples frequently had low-risk HPV genotypes that were not detected in tumors, but these low-risk genotypes were always a coinfection with high-risk genotypes. Oral gargle samples can be used to detect the majority of clinically relevant HPV genotypes found in oropharyngeal squamous cell carcinoma, but the interpretation of HPV detected in these samples should be assessed with caution for general cancer risk assessment given that sensitive assays can concomitantly detect low-risk genotypes.

Are associations between HIV and human papillomavirus transmission due to behavioural confounding or biological effects?

ObjectivesCohort studies have shown significant increased risk of HIV acquisition following human papillomavirus (HPV) detection and increased risk of new HPV detection in individuals with HIV infection, after adjusting for...

Three Important Findings From a Study on HPV "Real World" Effectiveness.

* Abbreviation: HPV — : human papillomavirus Early clinical trials of the human papillomavirus (HPV) vaccine demonstrated high vaccine efficacy against persistent infection with the vaccine-specific HPV subtypes, indicating that there will be significant reductions in the prevalence of HPV-related cancers and diseases with widespread vaccination.1 Now that the vaccine has been available for public consumption for more than a decade, researchers are shifting their focus to the vaccine’s effectiveness, that is, how the vaccine performs in real-world situations rather than in the highly controlled clinical trial environment. Several studies have been done in this regard in a variety of countries, indicating that the vaccine is performing well, as expected.2 However, given the range of factors that can affect vaccine uptake and effectiveness, many more studies with this focus are needed to truly understand the vaccine’s expected public health potential. The study by Spinner et al3 in this issue of Pediatrics adds significantly to this growing body of literature. In this study, researchers recruited 4 cross-sectional cohorts (ie, study “waves”) of adolescent and young adult women (ages 13–26 years) from 2 clinical sites over a period of 11 years. The primary outcome assessed was HPV infection status, and analyses were stratified by whether the women had been vaccinated against HPV. HPV infection outcomes were divided into a group corresponding to the 4 types covered by the quadrivalent vaccine (HPV-6, HPV-11, HPV-16, and HPV-18) and an additional 5 HPV types covered in the 9-valent … Address correspondence to Amanda F. Dempsey, MD, Adult and Child Consortium for Health Outcomes Research and Delivery Science, University of Colorado Denver, Anschutz Medical Campus, 13199 E. Montview Blvd, Suite 300, Aurora, CO 80045. E-mail: amanda.dempsey{at}ucdenver.edu

Impact of age on the overall survival benefits of anti-EGFR-containing regimens in head and neck squamous cell carcinoma: A meta-analysis of randomized controlled trials.

We conducted a meta-analysis to examine the associations of age, human papillomavirus (HPV) infection, and performance status with the overall survival (OS) benefits of patients with head and neck squamous cell carcinoma (HNSCC) after treatment with versus without epidermal growth factor receptor (EGFR) inhibitors. We systematically searched literature for randomized controlled trials comparing chemotherapy or radiotherapy with versus without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCCs. Hazard ratios (HRs) for OS were calculated using random-effects models for patient groups according to age (younger vs. older), HPV infection status (p16-positive vs. p16-negative), and performance status score (better vs. poorer). Five phase III trials with 2653 patients were included. EGFR inhibition was associated with a greater OS benefit in younger patients than in older counterparts (HR 0.70 vs. 1.05, P < 0.001). There were no apparent differences in OS based on HPV status (P = 0.860) or performance status score (P = 0.235). Largely consistent results were obtained following stratification by treatment strategy (i.e., chemotherapy and radiotherapy). Patient age appears to impact OS independent of HPV infection and performance status after adding EGFR inhibitor agents during HNSCC treatment. This finding may help design relevant clinical trials.