Specifically, these two tests almost perfectly agreed for detecting several types of HR-HPV, including HPV-16, -18, -35, -52, -58, and -59 . According to direct sequencing, PANArray HPV produced consistently higher sensitivities for detecting HR-HPV than HPV 9G DNA for either overall or individual genotypes of HR-HPV. Sensitivities and specificities for detecting HPV-58 were perfect (100%) with PANArray HPV. In conclusion, PANArray HPV is more effective than HPV 9G DNA in detecting HR-HPV. It is more useful for regions with high prevalent HPV-58 infection.The detection of high-risk human papillomavirus (HR-HPV) is important for early diagnosis of precancerous cervical lesion. The distribution of HR-HPV genotypes in East Asia is different from that in Western countries. HR-HPVs non-16/18 including HPV-58 are highly prevalent in East Asia. Thus, a variety of HPV tests that could identify individual genotypes have been widely used. HPV 9G DNA is a deoxyribonucleic acid-based chip test, while PANArray HPV chip is a peptide nucleic acid-based array. We compared the analytic performance of these two chips for detecting and genotyping HR-HPV using 356 liquid-based cytology specimens and evaluated their diagnostic accuracies based on direct sequencing. For identifying HR-HPV, PANArray HPV and HPV 9G DNA chips agreed with each other for 85.1% of samples. Overall strength of agreement between the two tests was substantial ( Although Papanicolaou (Pap) test contributes to incidence reduction of cervical cancer, Pap screening test alone was limited due to its low sensitivity and reproducibility for detecting high-grade squamous intraepithelial lesions (HSILs) of uterine cervix . Today, The distribution of HR-HPV genotypes in East Asia is significantly different from that in Western populations . HPV-58 PANArray HPV chip  is a peptide nucleic acid (PNA)-based test that could detect five more HR-HPV and eight more LR-HPV genotypes than HPV 9G DNA chip [9]. PNA In this study, we compared the performance of PANArray HPV and HPV 9G DNA chip tests for detecting and genotyping HR-HPVs. In addition, we validated genotyping results of these two tests by direct sequencing to compare their diagnostic accuracies.We collected data from our electronic pathologic database between July 2012 and October 2013. A total of 1632 women who were co-tested using ThinPrep pap  and HPV 9G DNA tests for routine screening were selected. Of 1632 women, 390 (23.9%) had histological confirmative diagnosis for uterine cervix during follow-up period. They did not have previous histories for gynecologic diseases or gynecologic procedures such as colposcopic biopsy, conization, or hysterectomy. Of these 390 women, 356 with adequate remnant DNA specimen were included in our study. All DNA specimens were stored at -70°C until they were re-assayed for HPV 9G DNA and PANArray HPV tests and direct sequencing. This study was approved by the Institutional Review Board of the Catholic University of Korea, Incheon St. Mary’s Hospital . No consent was given because data were analyzed anonymously.HPV 9G DNA tests were performed according to the manufacturer’s protocol , 8, 12. PANArray HPV tests were performed following the manufacturer’s instructions in a similar way of HPV 9G DNA chip [HPV genotypes of all 356 samples were completely examined by PCR and direct sequencing. PCR was performed using general primer MY09/11 . PCR prok) with 95% confidence intervals (CIs), proportions of positive and negative agreement, and McNemar’s P-values were calculated to assess agreement between HPV 9G DNA and PANArray HPV tests. The k value was interpreted as follows: 0–0.20, slight; 0.21–0.40, fair; 0.41–0.60, moderate; 0.61–0.80, substantial; and 0.81–1, almost perfect agreement. The proportion of positive agreement was calculated as twice the number of agreed positives/. In addition, the proportion of negative agreement was calculated as twice the number of agreed negatives/[2 or Fisher’s exact tests. Statistical significance was considered when p value was less than 0.05.Statistical analyses were performed using Analyse—it Method Evaluation Edition software version 5.30 . We analyzed the data according to genotyping results of 19 HPVs, which were commonly detected by both tests . Concordegatives). SensitiWe compared overall frequencies of 14 HR-HPVs and 5 LR-HPVs that could be identified by both tests .Overall positive rates for HR-HPV were higher  with PANArray HPV than those with HPV 9G DNA , regardless of HPV genotype . Among Hk = 0.68) when detecting any of 14 HR-HPV types. For detecting HPV-16, results of both assays almost perfectly corresponded to each other . Both assays also produced almost perfect agreements for HPV-18 results  and HPV-58 results . When considering HR-HPV genotypes of non-16/18/58, results of both HPV tests well agreed with each other at a rate of 88.2% (k = 0.74), which was similar to the overall concordance rate of both assays regardless of HR-HPV genotype. Statistically significant differences were seen in the detection of HPV-58, non-16/18/58 HPVs, and any of the 14 HR-HPV types . Regardless of HPV genotype, proportions of positive and negative agreement for HR-HPV status were 0.93 and 0.74, respectively. The proportion of positive agreement was higher than that of negative one for HPV-58. On the contrary, the proportion of negative agreement was higher than that of positive one for HPV-16, HPV-18, and HPVs non-16/18/58.Results of the two tests showed substantial agreement in 85.1% of all cases , similar to that for HPV-16, -18, and -58. For detecting HPV-59, both tests perfectly agreed (k = 1). For other HR-HPV genotypes including HPV-31, -33, -39, -45, -51, -56, -66, and -68, results of both tests corresponded well . Statistically significant differences were present between the two tests for the detection of HPV-31, -51, and -52 . The proportions of negative agreement for all HR-HPV non-16/18/58 types were more than 0.97 and their proportions of positive agreement were more than 0.90 except for HPV-33, -39, -56, or -68 which had a rate between 0.71 and 0.83.Type specific agreement of HR-HPVs non-16/18/58 detected by both assays are described in k = 1, both) and HPV-40 was detected with substantial agreement (k = 0.66). However, these two assays moderately agreed with each other for HPV-42 results (k = 0.45). They did not show agreement for HPV-34. Proportions of positive and negative agreement for HPV status of LR-HPV types including HPV-6 and HPV-11 were 1. For HPV-34, -40, and -42, proportions of negative agreement for HPV status were high (over a rate of 0.99) and their proportions of positive agreement were low (from 0 to 0.63).Among LR-HPVs, HPV-6 and HPV-11 were detected by both assays with perfect agreement  by direct sequencing. Of 232 HR-HPV-positive cases, 53 (22.8%) showed multi-infection of HR-HPVs. On the other hand, LR-HPVs were seen in 19  cases, 73.7% (14/19) of which were co-infected with HR-HPVs. HPV-16 was the most common type of HR-HPV , either alone or in combination with other types. HPV-58 was the second most common type of HR-HPV , followed by HPV-52 , HPV-35 , HPV-33 and HPV-51 , HPV-31 , HPV-68 , HPV-39 , HPV-18 , HPV-56 and HPV-66 , HPV-45 , and HPV-59 . Genotypes of LR-HPVs were infrequently observed .Of 356 samples, 124 without any genotype of HR-HPV confirmed by direct sequencing results were regarded as true negative. The other 232 samples were HR-HPV-positive by direct sequencing.p < 0.05 for all, Based on results of direct sequencing, results of both assays for HR-HPVs were classified as concordant, compatible, and discordant: 1) concordant, when all detected HR-HPV types perfectly agreed between the two tests (true positive); 2) compatible, if agreement was made for one or more but all HR-HPV types; and 3) discordant, when there was no identical HR-HPV genotype results between the two tests . Among 2vs. 92.4% for HPV-16, 100% vs. 80.0% for HPV-18, 100% vs. 73.5% for HPV-58, and 94.4% vs. 83.2% for HPV non-16/18/58, respectively). The specificity was higher with PANArray HPV for the detection of HPV-18 (100% vs. 99.4%). For other HR-HPVs, the two tests showed same specificities .Sensitivities and specificities of HPV 9G DNA and PANArray HPV chip tests in terms of detected genotypes of HR-HPVs are described in We compared results of HPV 9G DNA and PANArray HPV chip tests for 356 cervical ThinPrep PreservCyt samples and analyzed their diagnostic accuracies with reference standard of direct sequencing results. Although these two tests had similar techniques of target amplification and hybridization, PANArray HPV chip was superior to assay HR-HPVs than HPV 9G DNA with higher sensitivity and specificity. In particular, PANArray HPV perfectly detected HPV-58. Thus, this method may be more useful in countries with high prevalence of HPV-58 infection.Although non-16/18 HR-HPV genotypes also play a significant role in cervical neoplasia, current screening and management algorithms separate out these HPV types from HPV-16 and HPV-18 . The oveIn a monograph from International Agency for Research on Cancer (IARC), 12 HPV types  were classified as “carcinogenic to humans (Group 1)” and another 8 types  were classified as “probably or possible carcinogenic to humans (Group 2)” . PANArraIn conclusion, PANArray HPV had higher sensitivity and specificity in detecting HR-HPV than HPV 9G DNA. In particular, PANArray HPV perfectly detected HPV-58. Therefore, PANArray HPV is more effective than HPV 9G DNA for detecting HR-HPV. It is considered to be more useful for regions with high prevalence of HPV-58 infection, including Korea.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Distant metastases (DM) are a leading cause of death for patients with oropharyngeal cancer (OPSCC). The objective of this study was to compare the rates of DM after chemoradiotherapy (CRT) and radiotherapy alone (RT) in patients with human papillomavirus (HPV)‐positive and HPV‐negative OPSCC.In a retrospective population‐based study of 525 patients across Ontario, Canada, in 1998/99/03/04, we compared treatment effectiveness using cumulative incidence function curves and cause‐specific Cox regression models.Sixty of 525 patients developed DM. There was no difference in rates  between HPV‐positive and HPV‐negative patients or between CRT‐ and RT‐treated patients. CRT reduced the risk of DM for the 15% of all HPV‐positive patients with higher risk (T4 and/or N3) and not for HPV‐negative patients .The addition of platin‐based chemotherapy to conventional RT did not decrease the rates of DM in the majority of patients with HPV‐positive or in HPV‐negative OPSSC. Cetuximab was not used during 2003/04 in Ontario. The outcomes were site of first recurrence and any DM (first or second recurrence). The mean follow‐up time was 68.2 months from diagnosis. We report the proportions of DMs by HPV status and treatment. Logistic regression (DM yes/no) was used to investigate prognostic factors for any DM controlling for treatment, HPV status, T Category, and N Category. The baseline group was CRT, HPV‐negative, T1, and N0. Six patients who were lost to follow‐up were excluded noting that their mean follow‐up was 45.2 months. To account for the competing risks of death and first recurrence, we used Gray's test for equality of cumulative incidence functions to compare rates of DM by treatment for the HPV‐positive and HPV‐negative cohorts.Patients were grouped into high and low “risk of DM” based on combinations T and N Category as per O'Sullivan et al.3One hundred twenty‐five of the 525 patients recurred and the sites of first recurrence are outlined on Figure P‐value 0.07). DM occurred in 10.8% of the RT and 12.5% of the CRT patients. Overall, 200 patients died of their oropharynx, including 143 of the RT‐treated and 57 of the CRT group. One hundred eight patients died of other causes .The study population including HPV status and rates of any DM are presented in Table The risk factors for the development of DM based on all patients using logistic regression were N3 (OR 5.03 [1.14‐22.23]) and HPV‐negative status (OR = 1.94 [1.07‐3.52]) (data not included). The addition of chemotherapy did not have a statistically significant impact on the risk of DM (OR 1.06 (0.57‐1.98) over RT alone. Similarly for the HPV‐positive cohort only, the addition of chemotherapy to RT alone did not have a significant impact (OR 0.89 [0.41‐1.92]) over RT alone similar to the results for the HPV‐negative cohort (OR 1.37 [0.45‐4.15]).P = 0.34, P = 0.77). Similar results were obtained when the CIF curves only accounted for death as a competing risk .The CIF curves comparing CRT to RT for the HPV‐positive and HPV‐negative patients are presented in Figure n = 17). For the HPV‐negative patients, the risk factor was N2  and CRT had no statistically significant impact . Treatment, that is, CRT, did not influence the rates of DM for the HPV‐positive and HPV‐negative patients. Similar results were obtained when accounting for death only as a competing risk in the models.The results of the cause‐specific hazards model for all patients are presented in Table P = 0.01). Smoking status was not a statistically significant factor. The model for the HPV‐negative cohort showed similar nonstatistically significant results for treatment and smoking, and high “risk of DM” group was not statistically significantly different .Table 4specifically on the rates of DM. Based on 525 patients who were declared disease‐free after curative treatment and 60 developed DM. Between 10% and 15% of patients developed DM regardless of HPV status and treatment. CRT did not influence the rate overall, for the HPV‐positive cohort or for the HPV‐negative cohort. In the most recent meta‐analysis comparing CRT to RT alone, Blanchard et al.The objective of this study was to determine, in the absence of evidence, the impact of the addition of concurrent chemotherapy to conventional RT for patients with HPV‐positive and HPV‐negative patients with OPSCC Our results are consistent with those of O'SullivanThe strengths of this study are the inclusion of the complete cohort of “real‐world” patients from all treatment centers in Ontario, Canada, in a time when oncologists were HPV naive. For this study we used competing risk analysis. Other strengths include the unique design that used similar patients from different eras with different rates of HPV‐positive, the systematic data collection and quality of the HPV tissue testing. Testing was done at one independent laboratory  that was blind to patient identifiers, treatments, and results.The limitations of the overall study are carefully described in the original publications.There are six potential limitations for this substudy. First, we unfortunately did not abstract the location of the DM. This would be of particular interest, given reports of differences in DM sites.5Based on 525 patients with OPSCC treated for cure with either RT or CRT who were declared disease‐free at the end of treatment, we found no overall difference in the rates of DM comparing CRT with RT alone for HPV‐positive or HPV‐negative patients. HPV+ patients with the most advanced disease might benefit, but 90% of OPSCC patients regardless of HPV status need to be informed that there is no evidence for a reduction in DM with addition of platin‐based concurrent chemotherapy to conventional RT.The authors have no conflicts of interest to report.Dr Hall and Ms Griffiths were involved throughout the study design, data analysis, manuscript writing and manuscript revisions. Dr Hall had full access to all the clinical data in the study and takes responsibility for the integrity of the clinical data and the accuracy of the data analysis.


Specifically, organizations can be oriented toward a variety of values: learning, customer service, and even meetings. This paper explores a new and novel construct, organizational meeting orientation (the set of policies and procedures that promote or lead to meetings), and its relationship to perceived team meeting outcomes and work attitudes. An organization’s policies, procedures, and overall orientation toward the use of team meetings—along with the quality and perceived effectiveness of those meetings—set the stage for how teams develop and collaborate. Across two exploratory studies, we demonstrate that perceptions of an organization’s orientation toward meetings is associated with the perceived quality and satisfaction of team meetings, along with work engagement and intentions to quit. Employees who feel meetings lack purpose or are overused tend to be less engaged with their work and more likely to consider leaving the organization. Based on the findings, we conclude with a robust discussion of how meeting orientation may set the stage for team interactions, influencing how their team operates over time on a given project or series of projects. An organization’s orientation toward meetings is a new construct that may exert an influence on team dynamics at  Workplace meetings are essential to both the functioning of organizations and employees’ workplace experiences. Of the estimated 55 million meetings occurring daily in the United States, managers in large organizations are dedicating over three-quarters of their time preparing for, attending, leading, and processing meeting results . Among tAcross two studies, we propose that there are a number of ways in which individuals’ belief about the meeting orientation of their organization may influence how people view various meeting and organizational outcomes, which can subsequently influence team development over time. Specifically, building upon the original theory and conceptualization by Organizational orientations provide a potential competitive advantage for firms and examples include a market orientation or entrepreneurial orientation . A partigood meetings. Likewise, low meeting orientation organizations may hold fewer meetings, and meetings are not necessarily higher or lower quality than in organizations with a different meeting orientation. For example, meetings may be viewed negatively when a meeting culture inhibits employees from doing their job because they attend too many group and team meetings. Alternatively, additional meetings that provide employees the opportunity to pose questions to executive management can be viewed positively  and team meeting satisfaction (1b).The other three facets should have a markedly different relationship to meeting outcomes. Strategic use of meetings, or how much meeting attendees believe their organizations use group and team meetings to gather, exchange, and act on information, may be positively related with both team meeting effectiveness and team meeting satisfaction. People who believe that their organizations have meetings for a purpose, namely to interact with information, are likely to believe that those group and team meetings are effective and satisfying because the purpose is readily apparent and aligns with important, widely held assumptions about what a work meeting should be .Policy focus and rewards may also influence how supported group and team meeting attendees feel from the organization. Support in this case derives from perceived organizational support (POS) theory , which r Hypothesis 2: Policy focus (2a), rewards (2b), and strategic use of meetings (2c) will be positively related to team meeting satisfaction. Hypothesis 3: Policy focus (3a), rewards (3b), and strategic use of meetings (3c) will be positively related to team meeting effectiveness.M = 38.72, SD = 13.03). Of participants who provided information, 30% were men. Respondents worked in a variety of industries such as healthcare, education, and the military. Workers who supervised at least one employee comprised 48% of the sample.In exchange for course credit, students in an undergraduate psychology course recruited working adults to participate in the study through Qualtrics, an online survey tool. A total of 22 students sent invitations to potential participants, 174 of whom finished the survey. Thus, the final sample consisted of 174 well-educated adults (59% held a four-year degree) who ranged from 19 to 68 years old . Cronbach’s alpha for this measure was 0.83.Participants indicated how effective they felt their last meeting was across six areas  using a 5-point Likert scale (1 = strongly disagree) to 5 (strongly agree). Cronbach’s alpha estimate of internal consistency was 0.85.Meeting satisfaction was measured using a 6-item measure developed by strongly disagree) to 5 (strongly agree). Participants reported on several factors of their last workplace meeting including meeting type, purpose , and numDescriptive statistics, alpha estimates of internal consistency, and correlations between study variables are included in F = 4.47, p = 0.002, R2 = 0.11.Hypotheses 1a and 2a,b predicted that overuse would be negatively related to team meeting effectiveness, whereas policy focus, rewards, and strategic use of group and team meetings would be positively related to team meeting satisfaction. In order to separate the influence of demographic factors on meeting satisfaction, the first step of the regression model included age, number of meetings attended per week, supervisory status, and job level as control variables, following best practice recommendations for statistical controls . MeetingF = 7.46, p < 0.001. Results indicated that overuse  and strategic use of meetings  were significantly related to meeting satisfaction, thus providing support for hypotheses 1a and 2c. Policy focus  and rewards  were not related to meeting satisfaction so hypotheses 2a and 2b were not supported.In the second step of the analysis, the meeting orientation dimensions were jointly added to the model in order to test the relationships of interest and accounted for an additional 18% of variance in team meeting satisfaction, The analytic strategy described for team meeting effectiveness as the outcome variable was followed to test hypotheses related to team meeting effectiveness. Hypothesis 1b predicted that overuse would be negatively related to team meeting effectiveness, and hypothesis 3a,c proposed that policy focus, rewards, and strategic use of meetings would be positively related to team meeting effectiveness.F = 0.72, p = 0.56, R2 = 0.02. The meeting orientation facets were then added to the model in the second step and explained an additional 29% of meeting effectiveness variance, F = 8.60, p < 0.001. Overuse  and strategic use of meetings  were significantly related to meeting effectiveness, which provided support for hypotheses 1b and 3c. Policy focus  and rewards  were not related to meeting satisfaction so hypotheses 3a and 3b were not supported. Complete results analyses are displayed in As in the earlier test of meeting satisfaction, the first step of the regression model included age, number of meetings attended per week, supervisory status, and job level as control variables. These demographic variables did not account for a significant portion of the variability in meeting effectiveness, The dimensions of meeting orientation may uniquely relate to employee work-related attitudes. According to However, certain facets of meeting orientation may be advantageous or disadvantageous relative to employee attitudes. For instance, employees who believe that their organization overuses group and team meetings—meeting overuse is a negative facet of meeting orientation that refers to the degree to which employees believe the organizations has too many meetings—may have poor work attitudes. Building from social exchange theory and POS theory, if employees believes that the organization does not value their time and wastes it on unnecessary group and team meetings, the employees are likely to have less favorable work attitudes. These positive (or negative) interactions may represent something beyond the dyadic relationship because leaders represent a proxy for the organization . Subordi Hypothesis 4: Overuse will be positively related to ITQ. Hypothesis 5: Overuse will be negatively related to work engagement.An organization’s emphasis on meeting orientation may contribute to both employee engagement and ITQ. Previous research demonstrated that employee engagement can be fostered in the context of workplace meetings . SpecifiIn contrast, the group and team meeting context may also allow employees to engage in withdrawal behaviors—temporarily or permanently separating from their work roles . For exa Hypothesis 6: Policy focus (6a), rewards (6b), and strategic use of meetings (6c) will be negatively related to ITQ. Hypothesis 7: Policy focus (7a), rewards (7b), and strategic use of meetings (6c) will be positively related to work engagement.Although we expect that an organization’s meeting orientation is related to various job attitudes, such as ITQ and work engagement, additional team factors seem relevant in the context of this framework. That is, if meeting orientation is optimal or suboptimal, there are team factors that may strengthen positive job attitudes or reduce negative job attitudes. One good condition for teamwork, perceptions of voice, may promote good team behaviors .Voice refers to the degree in which employees feel as if they have voice and freedom to discuss their concerns . Traditi Hypothesis 8: Voice in team meetings moderates the relationship between policy focus (8a) and strategic use of meetings (8b) and ITQ, such that the relationships will be more strongly negative when voice is low compared to high. Hypothesis 9: Voice in team meetings moderates the relationship between policy focus (9a) and strategic use of meetings (9b) and engagement, such that the relationships will be more strongly positive when voice is high compared to low.Participants in this study were recruited through a snowball sampling technique. Undergraduate students attending a large southeastern university enrolled in a psychology course were given a description of the study and Qualtrics link to share with full-time working adults in exchange for course extra credit. At the end of the survey, participants were encouraged to forward the survey link to other working adults who might be interested in participating. Participants were required to be employees in the United States who attend at least one work meeting per week. The sample consisted of 213 primarily White (66%) working adults, nearly split between males (48%) and females (52%).The 12-item meeting orientation scale  describenever to always. Engagement is typically examined as one factor due to high inter-correlations between the three dimensions  to 7 . Internal consistency for this measure was 0.75.Voice was assessed using a 5-item measure from Descriptive statistics, alpha estimates of internal consistency, and correlations between study variables are included in F = 0.02, p = 0.88, R2 = 0.00.Hypotheses 4 stated that overuse would be positively related to ITQ, whereas Hypotheses 6a,c proposed that policy focus, rewards, and strategic use of meetings would be negatively related to ITQ. Our control, number of meetings per week did not explain a significant amount of variability in ITQ, F = 9.81, p < 0.05, R2 = 0.19. Overuse  and policy focus  were significantly related to ITQ, which supported Hypothesis 4 and 6a. Rewards  and strategic use of meetings  were not related to ITQ, which did not support Hypotheses 6b or 6c.The meeting orientation facets were jointly added to the model in the second step and accounted for an additional 19% of variance in ITQ, R2 = 0.02, β = 0.66, p < 0.05, within the context of the entire model, F = 13.30, p < 0.05, R2 = 0.31, supporting Hypothesis 8a. Similarly, the interaction term between strategic use in meetings and voice was significant, ΔR2 = 0.02, β = 0.07, p < 0.05, within the context of the entire model, F = 13.38, p < 0.05, R2 = 0.31, supporting Hypothesis 8b. The interactions are depicted in We also hypothesized that the relationship between policy focus and strategic use of meetings and ITQ would be moderated by voice, such that the relationships would be stronger when voice was high compared to low. First, we calculated an interaction term between policy and strategic use of meeting sand ITQ. For the regression analyses, the first step contained the control, number of meetings per week, the second step contained voice, the third step contained the four meeting orientations, and the interaction term was entered in the final step. The interaction term between policy and voice was significant and accounted for a significant portion of variance in ITQ, ΔF = -0.08, p = 0.78, R2 = 0.00.Hypotheses 5 proposed that overuse of meetings would be negatively related to work engagement, and Hypotheses 7a,c stated that policy focus, rewards, and strategic use of meetings would be positively associated with work engagement. The first step with the control variable, number of meetings per week, did not explain a significant amount of variance in work engagement, F = 9.97, p < 0.05, R2 = 0.19. Policy  and strategic use of meetings  were significantly related to work engagement in the appropriate directions so Hypotheses 7a and 7c were supported. Overuse  and rewards , however, were not related to ITQ, which did not support Hypothesis 5 or 7b.The four meeting orientation facets were added to the model in the second step and accounted for an additional 19% of variance in work engagement, R2 = 0.00, β = 0.13, p = 0.70) or strategic use .We also hypothesized that the relationship between policy focus and strategic use of meetings and engagement would be moderated by voice, such that the relationship would be stronger for those with greater policy focus or strategically focused orientations. First, we calculated an interaction term between policy and strategic use of meeting sand ITQ. For the regression analyses, the first step contained the control, number of meetings per week, the second step contained voice, the third step contained the four meeting orientations, and the interaction term was entered in the final step. The interaction term was not significant for either policy  were more engaged in their work than employees in firms with a weak or negative meeting orientation. Policy, rewards, and strategic use were positively related to engagement, whereas meeting overuse was negatively related. Similarly, our findings indicate that meeting orientation is also related to employee ITQ. Greater meeting overuse was associated with higher turnover intentions, whereas strategic use of meetings was negatively related to ITQ.In Study 2, we expanded our focus to an important variable related to group dynamics: perceived voice in meetings. Employees who believe they have high voice in meetings are more likely to speak up to voice their concerns, thoughts, and opinions during a group meeting context . Indeed,Despite the strong pattern of results linking aspects of meeting orientation to group and team meeting outcomes and employees’ work attitudes, several of our hypotheses were not supported. Controlling for number of meetings attended per week and the unique contribution of each facet of meeting orientation, policy focus and rewards explained unique variability only in work engagement. One reason for the relatively small contributions of these facets may be that these facets are more nebulous and less concrete than the others. For example, many organizations may not have specific policies that promote group and team meetings that employees can readily identify, meaning that the policy focus aspect of meeting orientation may not be useful or that the scale needs to be modified. Similarly, employees may have difficulty recalling specific rewards that their organizations offer to people who attend, lead, or organize team meetings.The results of these studies have several implications. First, although the fact of being unstudied does not necessarily warrant research into a new area, this paper provided preliminary evidence that facets of organizational meeting orientation are related, and in some cases quite strongly, to important team meeting outcomes. For instance, prior research has demonstrated that satisfaction with meetings is a unique component of overall job satisfaction, even controlling for all traditional predictors of job satisfaction . Across Second, a variety of meeting scholars cf.  have sugThird, group and team meetings may serve as an important tool which allows for the facilitation of employee-supervisor interactions; guided by an organizational meeting orientation, these exchanges can be advantageous and disadvantageous toward work attitudes. For instance, if an employee evaluates the dyadic relationship positively, they may construe the interactions as an extension of the organization’s support, thus, may be more motivated to accomplish work tasks . HoweverOrganizations may have various organizational-level orientations  meant to advance the topic of interest . AlthougIn terms of managerial implications, our findings suggest that meeting leaders have the discretion to capitalize on planning and leadership behaviors associated with the various meeting orientation dimensions. First, managers should consider whether it is necessary to schedule a team meeting; if the information can easily be shared through email or one-on-one conversations, managers should take advantage of these alternative forms of communication rather than holding pointless meetings. Second, when calling employees for a necessary group or team meeting, leaders should only invite people for which the content is relevant. For instance, rather than a manager calling their entire team, managers can make decisions as to which collaborators are essential to accomplish the meeting’s purpose. Third, to respect everyone’s time, meeting leaders should use an agenda as a roadmap to guide and end the team meeting when the items are completed. Fourth, it is crucial that meeting leaders utilize group and team meetings as a strategic tool to gather, disseminate, and respond to information relevant to all attendees.In terms of organizational implications, our findings suggest that organizations can use meeting orientation as a competitive advantage to guide skills, behaviors, and processes of leaders and employees. First, organizations should assess where they fall within the four dimensions of meeting orientation; if necessary, organizations should make adjustments to the policies, procedures, and practices surrounding their meeting usage. Second, since group and team meetings may be perceived as interruptions from daily work tasks, organizational leaders should instruct on when it is appropriate to hold team meetings. Third, organizations should institute policies, procedures, or training programs to instruct managers on good team meeting practices .The findings of the study are an encouraging first step in the exploration of organizational level attitudes toward team meetings that can affect individual level outcomes, but a number of limitations must be considered when interpreting these findings. Most importantly, data examined in this study is cross-sectional in nature, which precludes drawing causal connections between variables, especially considering the scant literature and theorizing on meeting orientation generally. Furthermore, the cross-sectional, same-source data also makes the findings less potent. Although the models in this study depict meeting orientation leading to team meeting effectiveness, team meeting satisfaction, ITQ, and work engagement, it is entirely plausible that the opposite is true. For example, perhaps people who think their meetings are effective and satisfying believe that the organization strategically uses (and does not overuse) meetings. Future research should examine meeting orientation using a variety of data sources, such as objective, behaviorally based measures of team meeting effectiveness or quality, and relate these two ratings of meeting orientation.Second, participants in this study represented a wide variety of organizations and were therefore each rating different organizations and different meetings. This is both a strength  and limitation  of the studies. To strengthen the design, future research on meeting orientation should contain a combination of individual and organizational levels of analyses, such that multiple data points are collected within each organization to make comparisons across organizations possible. As meeting orientation is inherently an organizational level factor, of interest to meeting researchers should be how organizations with different meeting orientations conduct and approach group and team meetings, and another area that he may be how individuals with in those organi zations perceive their meetings.Third, we implemented several strategies to mitigate concerns of common method variance given the cross-sectional nature of these studies . To reduAlthough the forgoing studies substantiate the existence of meeting orientation, they cannot directly speak to how meeting orientation impacts teams at initial formation and over time as they work in the organization. However, an organization’s orientation toward the use of team meetings in each of the four facets could have implications for the ways in which teams develop and evolve over time. In our approach to meeting orientation, a “positive” orientation includes high levels of strategic use, policy focus, and rewards, whereas a negative orientation is low on those facets and high on overuse. Based on the findings reported in this paper, we develop several propositions below regarding meeting orientation. With respect to how teams develop over time, a positive meeting orientation may play an important role in establishing the working environment of new teams, acclimating new team members to the team and organization’s culture, fostering high-quality interactions with co-workers, enhancing commitment to the team and organization, and creating more stable team memberships.Future research on team meeting orientation should focus on the measurement of full teams given that perceptions of meeting quality may be driven by the role held by the meeting participant . Decades of organizational research have compared self, peer, and supervisor ratings on perceptions of traits, skills, abilities, and performance levels; at best, self-ratings demonstrate a moderate relationship to objective measures . Team meProposition 1a: Newly constituted teams will perform better in organizations with a positive compared to a negative meeting orientation.Proposition 1b: Newly constituted teams performance will be optimized over time in an organization with a positive meeting orientation compared to a negative meeting orientation.Team member change is one of the most common forms of changes in teams . Team meProposition 2: Teams will experience less member change over time in organizations with a positive compared to a negative meeting orientation.A critical role of meetings in team functioning is to act as a space for knowledge transfer among team members . KnowledProposition 3: There is a positive a relationship between team information sharing over time and an organization’s meeting orientation.Unlike other organizational orientations , no empirical studies have investigated the consequences of meeting orientation. Studies 1 and 2 suggest that meeting orientation is related to individual perceptions of team meeting effectiveness, team meeting satisfaction, ITQ, and employee engagement even when controlling for several demographic variables. Although meeting orientation is not a predominant business aim, we see potential costs associated with meeting overuse but potential gains associated with strategic usage. Additionally, meeting orientation is an organizational level environmentally constraining construct with implications for new teams and for established teams. Over time, the meeting orientation of an organization has the potential to enable or constrain team performance and our hope is that the studies and propositions here will spur additional work by researchers on this important meeting science domain.The institutional review board (IRB) for the University of Nebraska Medical Center and the University of Nebraska at Omaha approved an exempt IRB protocol for the forgoing study. In this case, consent was given by participation in the surveys provided and completion of the survey was that consent and no identifying information was asked on the survey.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Infection with high oncogenic risk human papillomavirus types is the etiological factor of cervical cancer and a major cause of other epithelial malignancies, including vulvar, vaginal, anal, penile and head and neck carcinomas. These agents affect epithelial homeostasis through the expression of specific proteins that deregulate important cellular signaling pathways to achieve efficient viral replication. Among the major targets of viral proteins are components of the DNA damage detection and repair machinery. The activation of many of these cellular factors is critical to process viral genome replication intermediates and, consequently, to sustain faithful viral progeny production. In addition to the important role of cellular DNA repair machinery in the infective human papillomavirus cycle, alterations in the expression and activity of many of its components are observed in human papillomavirus-related tumors. Several studies from different laboratories have reported the impact of the expression of human papillomavirus oncogenes, mainly E6 and E7, on proteins in almost all the main cellular DNA repair mechanisms. This has direct consequences on cellular transformation since it causes the accumulation of point mutations, insertions and deletions of short nucleotide stretches, as well as numerical and structural chromosomal alterations characteristic of tumor cells. On the other hand, it is clear that human papillomavirus-transformed cells depend on the preservation of a basal cellular DNA repair activity level to maintain tumor cell viability. In this review, we summarize the data concerning the effect of human papillomavirus infection on DNA repair mechanisms. In addition, we discuss the potential of exploiting human papillomavirus-transformed cell dependency on DNA repair pathways as effective antitumoral therapies. Papillomaviridae family and, to date, over 200 different types have been identified and their genomes completely sequenced Human papillomaviruses (HPVs) are small, nonenveloped viruses with a genome composed of double-stranded circular DNA of approximately 8 kbp Approximately 40 HPV types infect the mucosa and skin of the anogenital tract. These HPV types are further subclassified as low or high risk according to their association with the development of cervical carcinoma and its precursor lesions. Low-risk HPV types, such as HPV6 and HPV11, are associated with genital warts and low-grade cervical intraepithelial neoplasia (CIN) To establish a productive infection, HPVs have to reach cells from the basal layer of the epithelium. These are the only keratinocytes of the tissue that proliferate and express the DNA replication machinery. Therefore, they provide a permissive environment for initial viral genome replication. The virus can reach these cells through microwounds caused during sexual intercourse or at specific anatomical sites were the basal layer is readily accessible, such as the squamocolumnar junction (SCJ) of the cervix In high-grade CIN and HPV-associated tumors, viral DNA is frequently integrated into the host cell genome. Viral integration is an accidental event that usually disrupts the region were the E1 and E2 genes are located, leading to the loss of their expression. This constitutes a critical step in HPV-associated carcinogenesis since the loss of E2 leads to the upregulated expression of the main viral oncoproteins, namely, E6 and E7 It is estimated that approximately 291 million women are infected by genital HPV types worldwide. Each year, nearly 500,000 new cases of cervical cancer are diagnosed and over 270,000 women die from this disease around the world. Importantly, most of the cases (∼86%) and deaths (88%) occur in developing countries DNA contains the essential information for the formation and function of an organism, and its preservation is critical for survival. DNA is a fairly stable macromolecule; however, it suffers constant attacks from extracellular and intracellular factors that jeopardize its integrity. These factors include chemical and physical agents, infectious agents, highly reactive metabolic byproducts, and replication errors DNA repair is the process by which alterations in DNA are reverted. Usually, this involves the action of nucleases, helicases, ligases and DNA polymerases. Different specialized DNA repair mechanisms exist in which complex arrays of cellular proteins detect and repair different kinds of DNA lesions The DNA damage response (DDR) is composed of different signal transduction pathways that include damage sensors, signal transducers and effectors that act in a coordinated fashion to maintain genome integrity. Some DNA lesions activate specific sensors, such as the MRN complex (Mre11-RAD50-NSB1), replication protein A (RPA) or ATR-interacting protein (ATRIP), that trigger signaling pathways by the phosphorylation of apical protein kinases, such as ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR) and DNA-dependent protein kinase (DNA-PK). Different types of DNA lesions activate different kinases Many viruses, especially those with oncogenic properties, express proteins that affect the cell cycle and DNA damage repair regulatory pathways. Several studies have shown that during genome amplification, HPV proteins interact with different components of the cellular DNA repair machinery to activate or downregulate the expression or activity of factors of the ATM and ATR pathways. In 2009, Moody and coworkers showed that ATM activation is required for the productive genomic replication of HPV31 but not for episomal maintenance Importantly, many proteins from ATM and ATR pathways colocalize with HPV replication sites, further supporting the role of these factors in the HPV life cycle. Different studies have shown that E1 and E2 early proteins may activate the DDR, recruiting factors involved in DNA repair to process replication intermediates during viral genome amplification. Identified proteins at centers of HPV replication include 53BP1, ATRIP, OPbp1, p-ATM, p-H2AX, p-p53, ATR, CHK1, CHK2, PCNA, RPA, NBS1, BRCA1, RAD51, MRE11 and Ku70/80 The effect of specific HPV proteins on DNA repair pathways has been addressed by different groups. The HPV genome does not express proteins capable of mediating viral DNA replication and depends on the host cell machinery to achieve genome amplification. Therefore, it must induce the host cell to re-enter the S phase of the cell cycle to obtain access to the DNA replication machinery p110, p107 and p130 (pRb2). This interrupts the interaction of pRb proteins with members of the E2F transcription factor family. Once free from inhibition, E2F activates the transcription of several genes involved in S phase induction and progression, including cyclins A and E Among the main targets of E6 is the tumor suppressor protein p53. E6 forms a ternary complex with E6-associated protein (E6AP) and p53, altering p53's functional capacity and inducing the degradation of this cellular protein by the ubiquitin-mediated proteolysis pathway Due to their impact on different cellular pathways, HPV oncoproteins may also promote the accumulation of genomic alterations that contribute to malignant transformation Several studies have shown that ATM and ATR pathways are targeted by HPV oncoproteins. For instance, Banerjee et al. Other alterations in DNA repair systems associated with HPVs have been described by different groups. One report has shown that oral keratinocytes immortalized with HPV16 exhibit deficiencies in the NER system and, consequently, are unable to remove cyclobutane pyrimidine dimers (CPDs) induced by UV light 6-methylguanine DNA methyltransferase (MGMT) degradation via the ubiquitin/proteasome pathway in a process that requires the interaction of E6 with E6AP. The action of MGMT, which is impaired by E6, protects cells and tissues against the effects of alkylating agents The oncoprotein E6 also targets DNA repair pathways. For instance, epithelial mammary cells expressing this protein from HPV16 exhibit a reduced capacity for removing thymine dimers after exposure to UV light These observations show that HPV infection may increase the frequency of DNA alterations in the host cell and delay the removal of these alterations by targeting DNA repair pathways. In addition, by impairing cell cycle checkpoints and apoptosis, HPV oncoproteins cause sustained proliferation while preventing cell death. Collectively, these effects may lead to cellular alterations that give rise to precursor lesions with a tendency for malignant progression.During tumor evolution, cells acquire genetic alterations that may upregulate the expression of proto-oncogenes or induce gain-of-function mutations in these genes. In addition, mutations, deletions and alterations in the methylation pattern of promoter sequences may downregulate the activity of tumor suppressor genes. Cells harboring these alterations may have proliferative advantages and acquire other phenotypical alterations, such as the capacity to invade other tissues and organs In vitro data indicate that the activation of this pathway is mediated by E7 and is characterized by the formation of large FANCD2 foci and the recruitment of FANCD2 and FANCD1/BRCA2 to chromatin In hereditary cancers, mutations transmitted from progenitors predispose the host to the development of certain types of tumors and/or increase their sensitivity to carcinogens. This process may involve alterations in components of different DNA repair pathways. Several studies have suggested that mutations in this group of genes may act as cofactors in the establishment and progression of HPV-associated tumors. For instance, patients with Fanconi anemia (FA) or individuals carrying mutations in the breast cancer-associated (BRCA) gene exhibit a higher risk of developing HPV-associated cancerous lesions XRCC1, ERCC2, ERCC4 and ERCC1, at both the mRNA and protein levels, was downregulated in tumors and precursor lesions compared to samples from control subjects Alterations in the expression of genes involved in DNA damage sensing and repair are readily detected in HPV-associated cancers and precursor lesions. A study that analyzed the expression of genes involved in BER in 50 invasive cervical cancer patients and 40 squamous intraepithelial lesions (SILs) showed that the expression of Genome instability, in the context of HPV infection, may arise through different molecular pathways. A clear example of this is represented by the results of a study conducted by Kadaja et al. Chronic inflammation also plays a major role in cancer biology As previously stated, HPV oncogenes E6 and E7 play a critical role in HPV-mediated carcinogenesis by affecting major cellular processes. The consequences of HPV oncoprotein actions are reflected on cellular genome homeostasis. For instance, inhibition of the postmitotic checkpoint by high-risk HPV E6 and E7 is associated with the induction of polyploidy in human keratinocytes Alterations in the regulation of the cell cycle and the inhibition of proapoptotic factors are important underlying events in HPV-mediated genome instability. As expected, genomic instability is an early event during HPV infection that precedes viral integration, the development of associated lesions and their eventual progression to cancer Genome instability is probably not a consequence of HPV-mediated malignant transformation. However, it may favor the acquisition of genetic alterations that confer growing advantages to cells expressing viral oncogenes. In addition, the underlying mutator phenotype may allow transformed cells to adapt rapidly to the harsh conditions of the tumor microenvironment, contributing to tumor onset and progression.The data discussed above further support the established notion that the main mechanism by which HPV induces cell transformation is the targeting of p53 and pRb by E6 and E7, respectively However, the implementation of new therapeutic strategies to treat HPV-associated tumors is still required. In this context, the dependence of HPV-transformed cells on cellular DNA repair machinery may constitute a suitable target for intervention. In fact, inhibitors of selected molecules involved in specific cellular pathways have been applied for the treatment of cervical cancer in clinical trials The first case of synthetic lethality involving genes associated with DNA damage repair was with poly(ADP-ribose) polymerase (PARP) and breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 E6 and E7 form high-risk HPV types are pleotropic proteins that target an increasing list of cellular factors affecting their expression and function. As such, HPV-transformed cells exhibit major alterations in important signaling pathways and cellular processes, including several DNA damage repair mechanisms. This fact has consequences of clinical relevance. For instance, patients harboring HPV-associated head and neck squamous cell carcinoma (HNSCC) have significantly improved survival compared with patients affected by HPV-negative tumors. Although the molecular mechanisms underlying this difference are not completely understood, it is accepted that impaired DNA repair abilities, probably due to HPV oncoproteins action, play a major role Prati B prepared the text describing the effect of HPV on DNA repair machinery. Marangoni B prepared the text describing HPV-associated disease treatment strategies. Boccardo E prepared, revised and corrected all the text.


The incidence of abnormal cervical smears in the United Arab Emirates (UAE) is 3.6%. Data regarding specific high-risk HPV (hrHPV) genotypes are insufficient. Identification of hrHPV subtypes is essential to allow formulating effective vaccination strategies.n = 70), adenocarcinoma in-situ (n = 1) and squamous cell carcinoma (n = 4). Five tissue sections (10-μ-thick each) were cut and DNA extracted using the QIAamp DNA FFPE Tissue Kit. GenomeMeTM’s GeneNavTM HPV One qPCR Kit was used for specific detection of HPV 16 and 18; and non-16/18 samples were typed by GenomeMeTM’s GeneNavTM HPV Genotyping qPCR Kit.A total of 75 archival cervical cone biopsies with HSIL or higher lesions (2012–2016) were retrieved from a tertiary hospital, including HSIL (Median age was 34 years (range 19–58) with 70% UAE Nationals. hrHPV detected were 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, 66 & 68. hrHPV testing was negative in 12% of cases. Most common types were HPV 16 (49%), HPV 31 (20%) and HPV 18 (6.6%). hrHPV 16 and/or 18 represented 56% and rare subtypes 32%. Co-infection was present in 16%. Eight cases had two-viral subtype infections and 4 cases had 3 subtype infections. Multi-viral HPV infection was limited to hrHPV 16, 18, 31 & 33 subtypes.Infection by non HPV 16/18 is fairly common. A higher than expected incidence of rare subtype (20% hrHPV31) and multi-viral hrHPV (16%) were detected. This finding stresses the importance of this pilot study as currently only quadravalent vaccine is offered to control the HPV infection in the UAE population. Cervical cancer is the third most common cancer in females in the United Arab Emirates as per 2014 cancer incidence report in the emirate of Abu Dhabi . HPV infThe reported incidence of cervical abnormalities in cervical smears among women in the UAE is 3.6% in one study . The autInfrequent reports on studies identifying hrHPV types are available from the countries with somewhat similar geography and demography to the UAE. One such report included women presenting to an obstetrics and gynecology department at a hospital in Bahrain . It repoIn the ATHENA trial conducted in the USA on a large screening population, HPV 16 was reported as the most commonly associated hrHPV genotype with high-grade cervical lesions. In addition, the report also found an association of hrHPV 18 with half of the cases of in-situ and invasive adenocarcinoma of the uterine cervix .Data regarding the exact prevalence of various hrHPV types in the UAE population are limited. In 2008, the Health Authority of Abu Dhabi (HAAD) introduced HPV vaccination to all female students between the ages of 15–17. In addition, regular screening is recommended every 3–5 years to women aged 25–65 . Both FDMultiplex Real-Time Polymerase Chain Reaction-based (PCR) technique has recently been used to genotype hrHPV in the UAE population which allows simultaneous detection of multiple hrHPV genotypes .Knowledge of the specific hrHPV subtypes in the UAE population would not only help guide the formulation of proper cancer screening recommendations, but also assist in directing vaccination program strategies should the infection patterns deviate from the known national/regional/ and international epidemiologic data.Women diagnosed with cervical squamous intraepithelial neoplasias and cervical carcinomas were retrieved from the archives of the Department of Pathology at a tertiary care hospital  during the period from 2012 to 2016. Hematoxylin and eosin stained slides were reviewed by two of the investigators (MRQ and SAA) to confirm the diagnosis. Paraffin tissue blocks were retrieved on all cases except those with insufficient residual tissue. Cases were classified based on morphologic criteria for cervical neoplasia according to the World Health Organization (WHO) Classification of Tumors of Uterine Cervix . DemograFive representative tissue sections (each 10-μ-thick) were obtained from archival formalin fixed paraffin embedded (FFPE) tissue and placed in Eppendorf tubes. Sterile precautions were taken to avoid cross-contamination including changing cutting blades between cases and changing hand gloves. DNA was extracted using the QIAamp DNA FFPE Tissue Kit  at Women & Infants Hospital, Providence, RI, USA following the protocol recommended by the manufacturer. hrHPV genotyping was initially performed using multiplex PCR followed by Tag/Capsure probe hybridization at Memorial Hospital of Rhode Island, USA, a laboratory facility of Women & Infants Hospital. Subsequently the findings were ratified using a second detection method, GenomeMeTM’s GeneNavTM HPV One qPCR Kit  which specifically detected HPV 16 and18 and non-specially detected other rare subtypes. Subsequently all non-16/18 positive samples were typed on-site at GenomeMe, Canada, Richmond, BC, Canada using their GeneNavTM HPV Genotyping qPCR Kit.n = 70), adenocarcinoma in-situ (n = 1) and invasive squamous cell carcinoma (n = 4). The median age for HSIL and higher lesions was 34 years (range 19–58 years). UAE nationals constituted 53 cases (70%) of the study sample. Overall, hrHPV types detected were 16, 18, 31, 33, 35, 39, 45, 51, 52, 58, 59, 66 and 68 (Table n = 5), 18 (n = 2), 33 (n = 1) & 31 (n = 4) only. Co-infection consisted of genotypes of the same species in four cases. The remaining cases were infected by a combination of HPV genotypes consisting of different species (67% of cases). The species detected in this study sample included α9 species , α7 species , α6 species (HPV 66) and α5 species (HPV 51).The study was based on a total of 75 cases including HSIL  represented the most common HPV genotype in a screening sample of one million women. It was followed by HPV 51 (10.8%), 31 (8.7%), 52 (7.1%) and 18 (5.1%) .7% repre.A study in Bahrain reported HPV 16 and 52 as the most common types . In a siA study in Xinjiang (in north-western China) performed using routine Pap smear found that HPV 16, 58 and 39 are the most common genotypes . In contHPV 16 (38.9%) and HPV 58 (19.5%) were found to be the most common HPV genotype in cervical lesions and cervical cancer in the coastal region of Ecuador . In the A recent study in the UAE on cases of ASCUS  demonstrated the presence of hrHPV in 17.9% of cases . The autDespite many publications on HPV genotypes in different regions, there are still some gaps in available data on different HPV genotypes in various geographic regions and even within different regions of the same country. This variability may reflect differences in geographic, ethnic, socio-cultural, and religious practices of the region. In a recent study in the USA found that HPV 16 was less prevalent in Hispanic and Black women compared to White women .In the current study, HPV 16 was detected in the majority of cases (49%), whereas HPV 18 was detected only in 6.6% of the study sample, a significant deviation from what has been reported from the western world. Bruni et al. performed a meta-analysis on HPV infection prevalence dividing the studies into five geographic regions: worldwide, Americas, Africa, Asia and Europe. It included studies addressing both low and high risk HPV. They found that the most common HPV types worldwide were HPV 16 (3.2%) and HPV 18(1.4%) . In nortThe detection of HPV 31 in 20% of the samples examined in this study has potential implications in terms of vaccination strategies currently practiced here in the UAE. Currently, the two approved and available vaccines are the bivalent and the quadravalent vaccines which do not offer direct protection against HPV 31 –15. EpidCo-infection represented 16% of cases in the current study. It included cases infected with HPV 16, 18, 31, and 33. Infection with multiple species was present in 67% of the cases with co-infection. A study from India detected multiple genotypes in 23.41% of their HPV positive cases . InteresGinindza et al. found that infection with multiple hrHPV increases in patients with decreased immunity. In their study including HIV patients the prevalence of multiple hrHPV infection was 27.7% compared to 12.7% in non-HIV patients . It has All these studies reveal considerable geographic variation within the region and also from the Western studies. Other studies in the region demonstrated different results. It also appears that the rare subtypes appear to be prevalent in this region with different cultural and religious backgrounds. As each country in this region, or for that matter any other region of the world, is governed by independent administration despite their proximity it is imperative that the exact prevalence of hrHPV in a particular country/region should be available for effective control of this disease.The current pilot study is based on a limited number of samples. The finding ought to be ratified by larger, multicenter studies to get an actual overall incidence of the HPV subtypes in the country. The current study addressed cases that presented with HSIL or higher lesions. Thus, data on HPV type prevalence might be skewed toward the more aggressive lesions. One would argue that from a clinical perspective, the more aggressive lesions are those that need intervention to prevent progression and reduce the incidence of cervical cancer related mortality and morbidity. The sample of HSIL positivity might indicate that those cases with the less aggressive HPV types did not progress and may have resolved without progression. Thus, those cases would not need attention when vaccination and screening program recommendations are being implemented in the country.The incidence of hrHPV among the UAE population emphasizes the need for qualified well-trained healthcare professionals and gynecologists, who can perform colposcopic examination, detect and manage the disease appropriately; unfortunately, that need that has not been met here as off yet as reported by Ghazal-Aswad et al. .It is noteworthy to mention that even after using the most sensitive techniques available now, about 12% of UAE women studied did not show any detectable hrHPV in the tissues samples examined. This may imply that other carcinogenic factors may be responsible for these or there are more yet unrecognized hrHPV.The current findings are significant for the UAE population where the quadrivalent vaccine is currently used. This entails the possibility of limited protection in at least 20% of cases infected with HPV 31. In addition, the presence of co-infection by different HPV species warrants recommendation of vaccines with a wider coverage. Results will impact future screening and prevention recommendation by the Cervical Cancer Prevention Taskforce. This study will serve as a foundation for a larger study which appears prudent to ratify our findings.It is worth stating that risk of an HSIL lesion developing into invasive cancer depends to a large extent on the type of HPV. It has been shown that HPV 16 and 18 are detected in higher percentages in cases of invasive cervical squamous cell carcinoma in comparison to cases of LSIL. In addition, HPV 33 and 45 are similarly detected in invasive lesions. HPV 31 has an odds ratio of 3.4 of developing invasive cervical cancer. Thus, HPV type virulence is another consideration when vaccination and screening guidelines are addressed [In conclusion, this pilot study illustrates that HPV 16 and 31 are the most frequent HPV genotypes in cervical neoplasia in the UAE population. Co-infection with multiple genotypes is present in 16% of cases and consists of different HPV subtypes. Should these findings hold true on a larger population-based study it would be imperative to introduce a vaccine which would offer direct protection against both common and some of the rare subtypes of HPV infection in the United Arab Emirates.


P = 0.004) and recurrence-free survival  compared with HPV-negative counterpart. HPV status may play an important role in predicting the prognosis of patients with vulvar cancer. The HPV-positive vulvar cancer women might relatively have a better survival than HPV-negative ones.The purpose of this study was to estimate the prevalence of human papillomavirus (HPV) in vulvar cancer and determine whether positive HPV in vulvar cancer was associated with a better prognosis. Literature searches of Ovid EMBASE, PubMed, Web of Science and Cochrane Library were performed to identify related studies published from January 2000 to May 2017. A total of 33 studies including 7,721 subjects were selected in this meta-analysis. Overall, the HPV prevalence in vulvar cancer tissue was 34% (95% CI: 28%-39%) with 45% (95% CI: 28%-64%) in Asian populations and 34% (95% CI: 26%-42%) in Caucasian populations. The HPV-positive vulvar cancer was associated with better overall survival (hazard ratio = 0.64, 95% CI: 0.47–0.87;  Vulvar cancer is the fourth most common type of gynecological cancer and encompasses approximately 6% of all female genital tract malignancies. According to cancer statistics, there have been more than 6,000 cases and 1,150 deaths every year in the United States –6. AlthoNinety percent of vulvar cancers are squamous cell carcinomas , 9 and sThere are more than 100 types of HPV, and these are divided into 3 broad categories according to their oncogenic potential –14. The To our knowledge, the prevalence and prognostic value of HPV infection in vulvar cancer reported in previous studies have not been subjected to statistical pooling. In order to validate these personal observations, the aims of this study were to evaluate the HPV prevalence, determine the prognostic value of HPV and clarify which variables may be the underlying causes of heterogeneity in prevalence and prognostic value of HPV in vulvar cancer.Literature searches of Ovid EMBASE databases, PubMed, Web of Science, and Cochrane Library databases were performed from January 2000 to May 5, 2017. The main keywords used for the search were “carcinoma or cancer or malignancy or adenocarcinoma or neoplasm or carcinoma” and “vulva or vulvar or genito-urinary or genitourinary or genital or genitalia or perineum or perineal” and “papilloma virus or papillomavirus or papillomavirus infections or HPV”. The detailed search terms and strategies are shown in Inclusion criteria of this meta-analysis were as follows: (1) independently published study, investigating the prevalence of HPV in vulvar cancer patients; (2) a study investigated the association between HPV status and survival outcomes in vulvar cancer patients. The following exclusion criteria were also applied: (1) reviews; (2) case report or case series; (3) studies lacking enough information.Two investigators (Jianxin Zhang and Yang Zhang) independently performed the data extraction and quality assessment. The detailed information collected for each study mainly included first author, publication year, ethnicity, country, study period, types of vulvar cancer, type of tissue, HPV prevalence, HPV Types and detection methods, survival indicators, HR estimates, and follow-up time., The studies were merged into a unique extraction, if several publications were overlapped. If a study hadn`t reported the HR and its related 95%CI, Kaplan-Meier survival curves could be used referring to previously published methods , 17. AddThe quality of each eligible study was assessed by the nine-star Newcastle–Ottawa Scale (NOS). A study would be considered to have high quality with the NOS score equal or greater than seven scores. After data extraction and assessment, the information would be examined and adjudicated independently by an investigator (Zhenyu Zhang).Of the studies identified, the overall prevalence of HPV in vulvar cancer was analyzed, using the R software (version 3.4.1) and was estimated based on a random-effects model, in which the between-study variance was determined with the Der-Simonian Laird estimator. The results of the overall prevalence of HPV in vulvar cancer for all studies sorted by first author were presented using forest plots. The prevalence of HPV among vulvar cancer patients from each study was presented with exact binomial 95% confidence intervals (CIs).Chi2 and I2. I2 values of 25, 50 and 75% were defined as low, moderate, and high estimates, respectively. If no study heterogeneity existed (P>0.10 or I2<50%), the meta-analysis would use the fixed-effects model; otherwise, use the random-effects model. A HR<1 indicated a better survival outcome for HPV-positive while HR>1 indicated a worse survival outcome for HPV-positive. A P value less than 0.05 was considered statistically different. The sensitivity analysis was performed by deleting each study in turn to assess the consistency and quality of the results. The funnel plot and Egger`s test were performed to assess the potential publication bias.The meta-analysis of the prognostic value of HPV in vulvar cancer was carried out using Review Manager (RevMan) 5.3 analysis software . The association between HPV and survival outcomes in patients with vulvar cancer was estimated by calculating pooled HRs and related 95% CI. If the eligible articles did not report the HRs and 95% CI, they would be extracted according to previously published methods. The results were presented using forest plots. The study heterogeneity was assessed and presented by The process of literature search and study selection is summarized in Of the 33 studies, 9 studies reported the association between HPV infection and survival outcomes among vulvar cancer patients. The main characteristics of the studies included are summarized in A forest plot of the 33 eligible studies is shown in P = 0.2582).The subgroup analysis was performed depending on the ethnicity . The pooP = 0.004; P = 0.03; P = 0.66; P = 0.38; Nine studies provided data on the association between HPV status and survival outcomes in vulvar cancer patients. The pooled analysis showed that the HPV-positive vulvar cancer was associated with better OS  showed that there wasn`t a significant correlation between the prevalence and the OS in vulvar cancer for the 8 studies in our meta-analysis.To investigate the correlation between HPV prevalence and the OS in vulvar cancer for the 8 studies, we had plotted the prevalence and the OS (with 95%CI bars) for the 8 studies in a 2 dimension graph . The resQuality assessment of the 33 eligible studies is shown in A sensitivity analysis was performed for assessing the results of this meta-analysis (data not shown). Results of the sensitivity analysis showed that no significant alteration of the pooled incidence and HRs existed after removing a single study one by one, which indicated that the results of the prevalence and prognostic value of HPV in vulvar cancer were relatively stable and reliable.P = 0.487).The publication bias in the eligible studies, reporting survival outcomes of vulvar cancer was assessed by the funnel plot and Egger’s test. The shape of the funnel plot was approximately symmetrical . AdditioVulvar cancer is a rare type of gynecological cancer among women worldwide and is more commonly diagnosed in older women (over 65 years) . Based on the discovery and identification of prognostic biomarkers, the therapeutic approaches of vulvar cancer will evolve from standard radical resections to more individualized approaches . Because the definition of new prognostic variables might result in further individualization of the treatment of vulvar cancer, it would be useful to confirm more prognostic biomarkers of vulvar cancer to guide the individualized treatment.HPV was found to have a causal role in some types of gynecological cancers such as cervical cancer . It was I2 = 94%, P<0.01). The greater diverging prevalence rates of HPV positivity in these studies could generally be explained by different HPV detection methods , different case selection, or focusing on different types of HPV. In contrast to the established role of HPV as a risk factor, a significantly better survival outcome for women with HPV-positive tumors was found, compared to women with HPV-negative tumors. The pooled HRs of the associations between HPV status and OS, RFS indicated risk factors of 0.64 and 0.66 with significant P values, respectively. In addition, HPV-positive status tended to be associated with better DFS and DSS, although there was no statistical difference. This lack of significance could be partially explained by the small number of articles, as only two studies were included.In this meta-analysis containing 33 studies and 7,721 cases of vulvar cancer, the pooled prevalence rate of HPV was 34% (95% CI: 28%–39%) with large study heterogeneity  patients were reported to be less likely to have recurrence and there were no vulvar cancer related deaths, whereas p53-mutant positive patients had a greater probability of recurrence and were significantly more likely to die from vulvar cancer , 27. FurThere are some limitations of this meta-analysis. Firstly, some relevant studies were excluded in the meta-analysis due to incomplete raw data or publication limitations. Secondly, studies in other databases might have been lost. Thirdly, among the studies that reported the association between the HPV infection and survival outcomes in vulvar cancer, several studies that needed to calculate HR and its related 95% CI might have caused potential bias and imprecise values. Additionally, not all of the primary studies included in our meta-analysis analyzed the other many important prognostic factors comprehensively. Therefore, we could not determine whether HPV status is an independent prognostic factor for vulvar cancer. Furthermore, due to the large numbers of variables such as HPV types, detection methods and so on in studies about HPV prevalence and the limited studies about the prognostic value of HPV on vulvar cancer, we couldn`t determine the underlying causes of heterogeneity in prevalence and prognostic value.In conclusion, our study is the first meta-analysis to explore the prognostic value of HPV infection in vulvar cancer. We demonstrated a high prevalence of HPV-positivity in vulvar cancer cases which was similar with the previous study (53). The HPV status may act as a biomarker for predicting the prognosis of patients with vulvar cancer. More large-scale and well-designed studies are needed to confirm whether HPV status is an independent prognostic factor for vulvar cancer in the future.S1 Table(DOC)Click here for additional data file.S2 Table(XLSX)Click here for additional data file.


Reductions in persistent HPV infection and related diseases occurrence have been proved among vaccinated males. However, little was known on awareness of HPV and the vaccine in males, especially in high-risk subgroups such as men who have sex with men (MSM), in China. A multicenter cross-sectional study was conducted in MSM from 10 selected cities in mainland China. HPV awareness and vaccination acceptability were investigated through interviews and questionnaires. In total, 3057 eligible participants aged 18 years older from 10 cities were investigated. Only 20.6% (629/3057) of them had ever heard of HPV and 4.8% (146/3057) had heard of HPV vaccine. Factors that potentially influence willingness for HPV vaccination were found to be safety of the vaccine  and severity of HPV infection . After education, 97.8% (2882/2946) of participants would like to pay for HPV vaccination, and only a minority of them  would like to afford more than 2000 RMB. Our results showed that the awareness on HPV and the vaccine were quite poor among MSM in mainland China. To promote the application of HPV vaccination in male populations, appropriate information delivery and education on HPV infection and health should be enhanced as well as in females. Persistent infection of high-risk HPV genotypes  can cause cancers, including cervical cancer, penile cancer, anal cancer, as well as a fraction of head and neck cancers. Whereas low-risk HPV genotypes (including types 6 and 11) are pathogens of anogenital warts4. Several published studies have demonstrated that men who have sex with men (MSM) were at higher risk of HPV/HIV co-infection than heterosexual males due to their more common risky sexual behaviors, such as having unprotected anal sex and multiple sexual partners8. This leads to an increased risk of anogenital cancer among HIV-positive MSM10. Approximately 85% of anal cancers and 50% of penile cancers worldwide are attributed to oncogenic HPV13.The human papillomavirus (HPV) anogenital infection is one of the common sexually transmitted infections around the world14, in an effort to reduce the incidence of genital warts. The FDA added prevention of anal cancer both in males and females as an indication for vaccine use in December 201015. Several previous studies estimated that the vaccine protected against infection by HPVs 6, 11, 16, and 18 types that could cause over 90% of genital warts and 70% of cervical cancers17. An on-going study has shown the HPV vaccine is effective, safe, and well-tolerated among adolescent and young adult women19. Meanwhile, data from vaccination trials have shown reductions in persistent HPV infections and genital warts among vaccinated males21. As with females, HPV vaccination is likely to offer the greatest benefit when administered before the onset of sexual activity and HPV exposure. For MSM, a recent study showed that a national vaccination program could result in high uptake of vaccine, through sex health services22. Predictors of vaccine acceptability for males are similar to those that influence intention to vaccinate among females and include perceived susceptibility to HPV infection, sexual activity, perceived benefits of the vaccine, and perceived norms for vaccination23. Nowadays, more and more countries approve HPV vaccination for females. However, male HPV vaccination programs have been in debate because of the cost-effectiveness25. In nowadays China, HPV vaccine has not been approved to males yet. Little was known about the awareness of the virus and the acceptability of the vaccine in males especially in high-risk subgroups such as MSM.On October 2009, the U.S. Food and Drug Administration licensed a prophylactic quadrivalent HPV vaccine named Gardasil (Merck & Co. Inc.) for males aged between 9 and 26 years, previously licensed for females in 2006Our study aimed to investigate the knowledge and attitude towards HPV infection and HPV vaccination among MSM from mainland China by means of a multi-centered cross-sectional study. The potential factors which might influence the acceptability of HPV vaccination were identified in the study population as well.In total, 3154 individuals were interviewed and signed informed consents. After excluding 97 participants who lacked necessary information on sexual behaviors, 3057 (96.9%) eligible participants were included in data analysis. As shown in Table Data regarding knowledge of HPV are presented in Table Table Attitudes to the vaccination are shown in Table As shown in Fig. Supplementary Table To our knowledge, this is the first multicenter study from mainland China with a large sample size to investigate HPV awareness and vaccine acceptability among MSM. In total, 3057 eligible participants from 10 cities were investigated, only 20.6% of them had heard of HPV and 4.8% had heard of HPV vaccine. Factors that potentially influence willingness for HPV vaccination were found to be vaccine safety (54.2%) and severity of HPV infection (52.3%). Among those who would like to pay for HPV vaccination, 42.2% of participants would pay up to 500 RMB and only a minority of participants (2.5%) would afford more than 2000RMB.28. Nearly a half (43.7%) of the participants stated that they had never heard of genital warts, and much smaller number of them knew the correlation between HPV and genital warts and cancers. Lacking knowledge on HPV infection and related diseases will be a big challenge for the prevention and early diagnosis.The general knowledge on HPV was not satisfying in our study population. Only 20.6% of them have heard of HPV, it is significantly lower than the reports from western countries (73.6–93.0%)32. Apart from 20.1% of the study participants were self-reported bisexuality, another explanation could not be excluded. As only heterosexual marriage is currently legally allowed in China, approximately one fourth (23.6%) of the MSM population ever married due to pressure from family and society.This study revealed that 36.5% of the participants ever had sex with women. It was close to similar studies from China, with a proportion between 27% and 56%, but it was higher than a similar study in the USA, which showed 20% of the participants ever had sex with female partners34. The men who paid more attention to their own health and who believed that HPV vaccine could effectively protect from infection had stronger willingness to get vaccinated. The participants who had been diagnosed with genital warts or other STD showed higher HPV vaccine acceptability, which indicated that men who were sexually active men and had practice for STD diagnosis and treatment might more care about disease prevention. It is important to note that although knowledge of HPV and the vaccine was quite poor in the study population, their attitudes toward vaccination and intentions to be vaccinated may change from moderate to favorable after announcement and education. Therefore, MSM in China, as a high-risk population, need more knowledge of HPV and related diseases, so that they can better understand the benefits of HPV vaccine. And it is an important premise for active self-protection by behavior change and by available tools including HPV vaccine.In the present study, correlates of HPV vaccine acceptability were generally consistent with those identified in several previous studiesIn this study, HPV vaccine acceptability was uniquely predicted by several factors, including perceived benefits of the vaccine and severity of HPV infection to receive the HPV vaccine. It indicates that future HPV vaccination programs targeting at MSM should strengthen the health education on the risks of HPV infection and the benefits of vaccination. As we all know, current HPV vaccination campaigns typically highlight the benefits of the HPV vaccine for women. To some degree, it might be difficult to let all men be willing to receive a vaccine presented as a means of cervical cancer prevention. It must underscore the need for continued efforts aiming at removing barriers associated with HPV vaccination. In addition, high expense was found to be associated with diminished vaccine interest. What’s more, HPV screening is not an established clinical practice for men even for those with STD in China currently. All these difficulties to generalize HPV vaccination in high-risk male populations should be considered by public healthcare providers.35. Our study lacks the investigation and education on this important issue among the study population. Fifth, cross-sectional study itself has some limitations on association analysis. Despite the limitations above, our study has important strengths. We examine acceptability of HPV vaccination using a large-scale sample of participants and the response rate was high.When interpreting the results of the study, some limitations should be kept in mind. First, socio-demographic and risk behaviors of participants were collected by the questionnaires. Therefore, potential bias caused by inaccurate responses cannot be excluded. Second, because the information on HPV and HPV vaccine was given by the trained investigators before asking for the acceptability of HPV vaccination, we could not exclude the possibility that the results might be influenced by the training efficacy. Third, due to the potential limitation of enrollment methods, our study participants might not represent the general MSM population from the study sites. Therefore, selection bias can not be excluded. Fourth, during the past decade, infection with high-risk HPVs, in particular HPV 16, has been newly recognized as risk factor for head and neck cancers, specifically arising in the oropharynxIn conclusion, our investigation showed that awareness and knowledge on HPV and the vaccine were quite poor among MSM in mainland China. Most of the study participants cared more about the safety and efficacy of the vaccine, and showed higher willingness for HPV vaccination after education. Therefore, we need input much more public health resources to generalize knowledge of HPV and related diseases in the male populations especially in the subgroups under high risks of STD, such as MSM. Clinic trails evaluating HPV vaccine application in males should be urged to accelerate the approval of HPV vaccination in needed males in China.The present study was approved by the Ethics Committees of the Institute of Pathogen Biology, Chinese Academy of Medical Sciences (ref IPB-2011-1). Written informed consent was obtained from the eligible study participants before interview. All methods were carried out according to the approved guidelines set by the Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College.The present study was a cross-sectional study conducted in MSMs from 10 selected cities in mainland China . This study was coordinated by Institute of Pathogen Biology of Chinese Academy of Medical Sciences . Local non-government organizations involved in the enrollment of the study participants: Beijing Rainbow Volunteers Workstation, Chengdu Yongle Volunteers Workstation, Chongqing Tongxin Volunteers Workstation, Wuhan Volunteers Workstation, Guangzhou MSM network station, Tianjin Deep Blue Volunteers Workgroup, Shanghai guanggong Volunteers Workstation, Taiyuan kangtong Volunteers Workstation, Xi’an Tongkang Volunteers Workstation and Zhengzhou Sanhe Volunteers Workstation.36.According to the average income, the ten study sites were divided into three groups, including developed Cities , medium developed Cities  and less developed Cities  by socioeconomics level from national bureau of statistics of the People’s Republic of ChinaStudy participants were recruited through local non-government organizations above from the selected cities between December 2012 and July 2014. Multiple methods were used for recruitment including website advertisement, distributing flyers with study-related information at MSM-frequented venues , and eligible study participants were also encouraged to refer their peers to attend the study. Meanwhile, we encouraged eligible study participants to introduce their peers to attend the study. The inclusion criteria were males, ≥18 years old, ever having homosexual behaviors, having not been given HPV vaccine and willing to provide written informed consent.Trained interviewers collected sociodemographic information and self-reported health status by using a standardized questionnaire and administered in a private room. We collected sociodemographic information , sexual behavior, knowledge on HPV and HPV vaccine, and the acceptability of the HPV vaccine. Meanwhile, we also collected HPV awareness (whether they had heard of HPV) and the ways they heard about HPV. Moreover, we assessed HPV knowledge in the baseline and the post-test survey.Questionnaires were entered twice independently using EpiData software . After cleaning, we analyzed the data by Statistical Analysis System . All of the included participants were characterized by living site with respect to age, marriage status, ethnicity, education record, age at the first homosexual act, ever having sex with women, self-reported sexual orientation, and whether anal sex a regular sex behavior. Differences between sites in these variables were compared using Pearson’s chi-square test. Changes of HPV knowledge from baseline to post-test by condition were assessed by a mixed design analysis of variance. To estimate the willingness-to-pay of the HPV vaccine, we excluded those who refused to take vaccinate and those who would vaccinate only when the vaccine is provided for free, assuming that lower bound of willingness-to-pay cannot be less than zero. Then an interval regression model was fit to the intervals of the true willingness-to-pay using Proc Lifereg procedure in SAS 9.12.Human Papillomavirus awareness and vaccine acceptability among men who have sex with men from mainland China