Polymer pipes are used in the construction of underground gas, water, and sewage networks. During exploitation, various external forces work on the pipeline, which cause its deformation. In the paper, numerical analysis and experimental investigations of polyethylene pipe deformation at different external load values  were performed. The authors measured strains of the lower and upper surface of the pipe during its loading moment using resistance strain gauges, which were located on the pipe at equal intervals. The results obtained from computer simulation and experimental studies were comparable. An innovative element of the research presented in the article is recognition of the impact of the proposed values of the load of polyethylene pipe on the change in its deformation. Polyethylene plastics are used in various branches of global industry, mainly in extrusion and injection technology in the form of pipes, foils, and various types of packaging. The chemical, physical, mechanical and aesthetic properties of polymer materials depend on the conditions of use: temperature, load time, type of deformation, atmospheric conditions, UV radiation, design solutions, soil parameters in which the pipeline works, and external forces, e.g., car traffic ,7,8,9,10Polymer pipes are used in the construction of underground gas, water and sewage networks. This is due to their low weight compared to, e.g., steel pipes, which makes their transport and assembly much easier. Furthermore, polymer pipes are characterized by chemical inertness and very good mechanical properties ,12,13.Polymer pipe is a flexible material; therefore, it can be deformed at different external loads. The pipeline exploited in the soil react to the loads by deformation of its surfaces and by change in its cross-section. The value of the pipe deformation depends on the value of vertical force acting on the pipe and on the type and degree of soil compaction in which the pipeline is used ,15,16. TAt high loads, failure can occur due to the pipe wall breakage. A particularly dangerous case, from the point of view of the mechanical strength of the pipe, is pipeline installation at construction sites. At this stage, there is no working pressure in the pipe, which can cause it to stiffen. Furthermore, excavators, earth-filled lorries, move on such sites. High loading of pipelines can be caused by excessive soil layers directly above the pipe. This may lead to significant pipe deformation and, consequently, to pipeline damage even before its exploitation ,18,19.For this reason, it is essential to conduct experimental studies to prevent pipeline failure in real-life conditions. In regard to polyethylene material use, its thermal parameters are also very important ,21,22,23In the paper, numerical analysis and experimental investigations of polyethylene pipe deformation at various external load values were performed. The studies were carried out on a specially designed test stand. The lateral strains on the lower and upper surface of the pipe were measured at the following pipe loadings: 500, 1000, 1500, and 2000 N.In this paper, numerical analysis and experimental investigations of pipe deformation under the influence of various external load values were performed.2. Four load cases, 500, 1000, 1500, and 2000 N, were considered. The following boundary conditions were adopted in the tests:-Restraining of the system’s lower surface;-Restraining of the system’s side surfaces;-No restraint of the pipe.Computer simulation was carried out for a high-density polyethylene pipe (HD-PE) loaded by evenly distributed soil and an external force on the central part of the pipe surface. The numerical analysis was performed by using the ADINA System 9.3.4  program. The spatial model of the system includes a soil block with approximate dimensions of 400 mm × 3100 mm × 400 mm in which the analyzed pipe is located. Computer simulation was carried out for the pipe with the following approximate dimensions: outer diameter of 40 mm, wall thickness of 3.7 mm, and length of 2300 mm. The pipe was placed in soil at a depth of 315 mm. In the central part of the model’s upper surface, an evenly distributed load was placed over an area of 320,000 mmA diagram of the pipe–soil model is shown in The dimensioned pipe model with the marked section plane is shown in 1, σ2, σ3—main stresses, MPa;σo;θ—internal friction angle of soil, c—cohesion, MPa.The tested model of the pipe–soil system consists of 237,766 finite elements  and 377,615 nodes. The soil was modeled with the use of the elastic–ideally plastic Coulomb–Mohr model, which is one of the most frequently used models in soil numerical descriptions ,25,26,271, σ2, and σ3, the plastic area is limited by the side surfaces of the pyramid with the base of the hexagon . A plastic peephole was installed in the central part of the test stand’s side wall. The stand was used to perform an experiment of simulating the actual conditions that prevail during pipe deformation caused by the load. The test pipe was placed in the box on a sand bed. The same type of sand was used for backfilling of the pipe. The loads of 500, 1000, 1500, 1500, and 2000 N were applied to the upper surface of the backfill in the central part of the box. The value of deformation was recorded at the moment of pipe load. A scheme of the box is shown in Experimental investigations were carried out using a high-density polyethylene (HD-PE) pipe .On the lower and upper surface of the pipe, the strain gauges were placed at equal intervals of 120 mm with numbers from 1 to 20 . In this research, electrical and hose strain gauges by Microtechna (manufacturer of the strain gauges) were used, which were glued to the pipe walls. The sensors were used to record changes in the lateral strains of the pipe at different external loads. The strain gauges were made of one piece of wire which was glued to the paper or foil in a hose manner.R—the electrical resistance of the wire, Ω;δ—specific resistance of the wire, Ω;d—wire length, mm;LA—wire cross-sectional area, mm.In the resistance strain gauges used in the experiment, the strains were measured based on the relationship between electrical resistance and the length of the wire—Equation (2):The relative increment of strain gauge resistance is described in Equation (3):x) and (1 + εy) were deformed. The square cross-sectional area was initially equal to Ak = 1, and after deformation, it was as described in Equation (4):x—strain of the cross-section in the x-direction;εy—strain of the cross-section in the y-direction.εIn order to determine ∆A/A, a square with ABCD sides was determined on the cross-section of the wire. At the load applied, the lengths of the square sides with values of (1 + εThe relative change in the wire cross-section is described in Equation (5):x = εy = −νε, the relative change in the wire cross-section can be obtained using Equation (6):Excluding the product The relative increase in strain gauge resistance can be written as Equation (7):The relative strain is described in Equation (8):The value of the denominator in Equation (8) is the constant k, called the strain gauge constant, according to Equation (9) :(9)k=1+2k—strain gauge constant: 2.15;ΔR—relative increase in electrical resistance;R—the wire’s electrical resistance.The relative strain can be written as Equation (10):The value of the constant k in in Equation (9) depends on the sensor wire material, and it ranges between 1.6 and 3.6. For strain gauges used in this experiment, the constant k was 2.15 .Below are the results of the numerical simulation and experimental tests of polyethylene pipe loading.The results of the numerical analysis, illustrating the distribution of longitudinal strains of the tested pipe for different values of external load, are presented in The nature of the longitudinal deformations of the pipe is the same for each load case. Considering the top surface of the pipe, the following deformations were noted: negative in the middle part and positive at the ends of the pipe model. On the pipe’s lower surface, the following deformations were noted: positive in the middle part and negative at the ends of the pipe model.−4 on the upper surface, and 1.7 × 10−4 on the pipe’s lower part. At the load of 2000 N, this value is approximately 3.3 times greater.The distribution of transverse deformations of the tested pipe is of the same nature in each analyzed load case. On the lower and upper surface of the pipe, in its middle part, the deformation values are negative, while at the pipe ends, the values are positive.−5, while in the lower part, it is equal to −7.5 × 10−5. In the case of loading of 2000 N, an increase in the deformation value of −2.8 × 10−4 at the top was observed, while an increase in the deformation value of −3 × 10−4 at the bottom of the pipe in relation to the load of 500 N was noted. The values of longitudinal and transverse deformations are small, falling within the yield point of polyethylene [The highest values of negative deformations in each load variant occur in the central part of the pipe. Along with the increase in the value of the soil load, the lateral deformation increased. It can be concluded that, as in the case of longitudinal deformations, the smallest values of pipes transverse deformations occur at the load of 500 N. On the upper surface of the pipe, the value is equal to −7.3 × 10ethylene ,33. TherThe results of experimental tests of longitudinal deformation of the pipe at the considered loads confirmed the results obtained during the numerical analysis, and they have the same trend. The highest negative deformation appeared to occur on the pipe’s upper surface, while the maximum positive deformation was recorded in its lower part.As in the case of longitudinal deformations of the pipe, the results of the experimental tests also agree with the results obtained from the computer simulation. The nature of deformations is the same in each analyzed case. On the lower and upper surface of the pipe, the greatest negative values of deformation always occur in the center of the pipe. In turn, deformations with a positive sign are located at the pipe ends. In each load variant, the positive deformations are slightly greater on the pipe’s upper surface.x and εy observed in the results obtained from the simulation and the experiment for the central part of the pipe .x between the results obtained from the computer simulation and the results of experimental tests concerns the upper surface of the pipe for a load of 1000 N. The maximum value of deformation obtained from the experiment is 7.43 × 10−5 smaller than the value obtained from the simulation. The greatest difference in the value of the maximum deformation εy was recorded for the lower surface of the pipe at the load of 1500 N. The difference in values between the experimental test and the numerical analysis is 2.98 × 10−5.The largest recorded difference in deformation εThe slight differences in the obtained results confirm the high accuracy of the computer simulation and the experimental research.It is necessary to conduct research on changes in pipe properties as a result of degradation processes. The results of such studies may contribute to the prediction of failure-free operation of pipelines, as well as earlier planning of their repairs or replacements, which is reflected in the reduction of downtime in the supply or receipt of utilities, both from households and production companies.Conducting experimental tests and numerical simulations allowed for a comparative analysis between them and recognition of the impact of the proposed values of polyethylene pipes’ load on the change in their deformation. The high consistency of the results of computer simulations with the results of experimental tests obtained in the work indicates the appropriate application of the models in the problem under consideration .The authors plan to conduct further research on the change in the mechanical properties of polyethylene pipes after aging, corresponding to operation of a few years .


Rotondo et al.; Zhou et al.). Some small DNA tumor viruses, which are ubiquitous in human populations, may represent a risk for the cancer onset in those patients with immune system impairments. The detection of small DNA tumor viruses in patients affected by cancers and understanding of their mechanism of cell transformation may allow precise treatment options, such as surgery, radiotherapy, immunotherapy, and pharmacotherapy with specific antineoplastic agents and biological drugs. Indeed, in recent years the precision/personalized medicine improved the patient's outcome. Investigations on the association between human cancers and small DNA tumor viruses have become significant for the scientific research in the field of oncology and virology. Data obtained in this oncological area are already employed to address therapeutic strategies to selected targets. In this Research Topic, a collection of reviews was published with the aims to favor (i) the spread of the basic knowledge of this field and (ii) the translational medicine for the distinct cancer types.It has been estimated that ~30% of human tumors are linked to oncogenic viruses. Different human malignancies, including oropharyngeal carcinomas, hepatomas and brain tumors, have been found to be associated to small DNA tumor viruses, such as human papillomaviruses (HPV), hepatitis B virus (HBV) and polyomaviruses (PyV), respectively , and with medulloblastomas and gliomas of different histotypes, together with the biology and physiopathology of this PyV. Provenzano and Allayeh in their opinion article report on the association between prostate cancer (PCa) and BK polyomavirus (BKPyV), as well as other PyVs. A general overview is provided about suitable and feasible technologies to be used for PCa diagnosis/prognosis. Specifically, this article addresses the importance of isolating and analyzing the biomarkers in liquid biopsies. Authors indicate that these new technical approaches seem to be promising for cancer diagnosis, prognosis and prediction. Kervarrec et al. focused their review on the Merkel cell carcinoma (MCC) and Merkel cell polyomavirus (MPyV). MCC is a primary neuroendocrine carcinoma of the skin, whereas MCPyV is a new human polyomavirus (HPyV), which DNA was found be integrated into the host genome leading to MCC oncogenesis. The nature of the cell in which MCC oncogenesis occurs is actually unknown. So far, several hypotheses have been postulated. For instance, epithelial as well as fibroblastic or B-cell origin of MCC has been proposed mainly based on phenotype similarities shared by MCC and these potential ancestries. The Touzé's group provides a comprehensive review of the current knowledge of the MCC histogenesis. Rotondo et al. in their review on the association between human cancers and the oncogenic polyomavirus Simian virus 40 (SV40) report on new data obtained with indirect ELISA tests with synthetic peptides as mimotopes/specific SV40 antigens. Serum samples from oncological patients had a higher prevalence of antibodies against SV40 compared to healthy subjects. These innovative immunological results strengthened the association between SV40 and specific human tumors, while at the same time allowed to circumvent controversies arisen on data obtained by early molecular biology studies. In his review, Gheit reports on the association between mucosal/cutaneous cancers and oncogenic human papillomaviruses (HPVs). More than 200 different HPVs have been listed so far. Based on epidemiological data, some HPVs are classified as high-risk (HR) HPV types. HPVs are the etiological agents of anogenital cancers, while a HPV subset of head and neck cancers. The cutaneous HPV types are present on the surface of the skin in the general population. However, beta HPVs seem to play a role, together with ultraviolet (UV) radiation in non-melanoma skin cancer (NMSC). Molecular mechanisms showed that HPV oncoproteins E6/E7 alter pathways involved in the host immune response to establish a persistent infection and by promoting cellular transformation. Zhou et al. reported on the HPV strategy to evade the immunological system. They recalled that HPV persistent infection initiates ~5% of all human cancers, including cervical and oropharyngeal cancers. HPV vaccines prevent HPV infection, but do not eliminate existing HPV infections. HPV-induced hyperproliferation renders epithelial cells less sensitive to immune attack, and impacts upon the efficiency of the local immune system. These observations have significance for the design of therapeutic HPV cancer immunotherapies.In an overview on JC polyomavirus (JCPyV), In conclusion, authors of this Research Topic addressed their reports on the mechanisms of cell transformation operated by small DNA tumor viruses, such as PyVs and HPVs. These reviews indicated novel diagnostic tools, new therapeutic targets and strategies to be transferred to the clinical practice with the aim to cure tumors associated with oncogenic viruses.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with the author at time of review.


HPV-infection in patients with HNSCC is reportedly correlated with sexual behavior, age, and tobacco/alcohol-consumption. HPV-infections of the oral cavity are regarded as sexually transmitted. Comparable data of patient populations outside the U.S. are sparse or missing.Questionnaires regarding sexual behavior, education tobacco- and alcohol-consumption, were given to 28 patients with tonsillar hyperplasia (H) and 128 patients with tonsillar carcinomas (CA), all with tissue-typed HPV-DNA-status performing PCR. Answers were correlated among groups and HPV-status.106 questionnaires were analyzed. Comparisons between H- (n = 25) and CA- (n = 81) patients showed that CA-patients were older (61.1yrs ± 9.3) than H-patients ; had a lower educational level (p = 0.0095); and lower number of sexual partners . All groups showed a significant correlation between smoking and lack of HPV-DNA-positivity (p = 0.001). Further Fisher's exact tests and logistic regression analysis revealed in all 106 patients no significant correlations between tissue-HPV-status and the analyzed parameters.Despite the limited sample size, we were able to confirm the established correlation between smoking and tissue-HPV-status. The correlation between sexual behavior and HPV-infection was not confirmed. No consensus exists in the literature about the latter. Our data does not support the strict classification of oral HPV-infections and HPV-driven HNSCCs as STDs. •Questionnaires from 81 TSCC and 25 tonsillar hyperplasia (H) patients were analyzed.•No correlation between HPV positivity and sexual behavior was found.•HPV positive H had both less sexual partners and oral sex than HPV negatives (trend).•In TSCC sexual partners and oral sex were similar irrespective of HPV status.•Incongruent data about sexual behavior, HPV transmission and cancer transgression. In the 1980s Harald zur Hausen and co-workers  establisThe current study in a northern German population aimed to a) investigate whether patients suffering from HPV-positive TSCCs show differences in their sexual behavior, gender, age, education, tobacco and alcohol intake when compared to HPV-negative patients; b) investigate whether HPV-positive patients suffering from tonsillar hyperplasia, specifically with obstructive sleep apnea syndrome, show differences in their sexual behavior, gender, age, education, tobacco and alcohol intake when compared to HPV-negative patients. Lastly, c) we compared the incidence of the above social parameters between the two patient groups and d) in an exploratory analysis all HPV-positive patients were compared to all HPV-negative patients, irrespective of their disease to increase our power to observe a correlation between demographic variables and the presence of HPV.22.1In a prospective, consecutive setting, patients suffering from tonsillar squamous cell carcinomas (TSCC) or obstructive sleep apnea syndrome (OSAS) due to tonsillar hyperplasia, were enrolled in this study, when treated by surgical resection at the ENT Departments of the University hospitals in Kiel and Rostock, the municipal hospital Oldenburg and at the ENT Department of the Asklepios Clinic Hamburg-Harburg. All patients had to be 18 years of age or older. Paper-based questionnaires regarding, age, gender, smoking and drinking habit, sexual orientation, lifetime number of sexual partners, frequency of oral sexual intercourse, and education were prospectively given to 28 patients with tonsillar hyperplasia (H). In addition, 128 patients with tonsillar squamous cell carcinoma (TSCC) were questioned. 53 patients in this group were enrolled in a prospective manner (pCA). A further 75 TSCC-patients with previously determined HPV-status . The selThe study was approved by the local Ethics committee . Patients gave written informed consent.2.2The HPV-DNA status in all tonsillar tissue samples was also determined in Kiel using the following experimental procedures: DNA was extracted from 4 to 6 consecutive 5 μm FFPE-sections using the ExpressArt Mag RNA + DNAready kit , according to the manufactures protocol (for the H- and pCA samples) and the QIAamp DNA Mini Kit; Qiagen, Hilden, Germany for the rCA samples. All necessary validation experiments were performed to assure comparability of the results. In all cases 50 ng of DNA per sample was used to perform PCR reactions using the primers GP5+/GP6+ as described previously . DNA intAll tissue samples with detectable HPV-DNA were defined as HPV-positive.2.3Firstly, demographic differences between the two cancer patient cohorts were analyzed using Fisher's exact tests and the demographic characteristics of the cancer patients of both cohorts  and the patients with tonsillar hyperplasia (H) were compared using Fisher's exact tests. Student's t-test was performed to assess age-related differences between pCA and rCA patients and between all CA- and H- patients . The relationship between HPV positivity and the demographic variables was then assessed within each disease group and was finally assessed in an exploratory analysis in the two groups combined using Fisher's exact test. Additionally, logistic regression analysis was performed to further explore the association between the demographic variables and tissue HPV-positivity in all patients, with additional adjustment for age and smoking habit. p-values ≤0.05 were considered statistically significant, confirmed by Bonferroni post-testing for multiple comparisons where appropriate.33.1In total 28 questionnaires were prospectively given to patients with tonsillar hyperplasia with a return rate of 89% (n = 25). A total of 128 questionnaires were given to TSCC-patients. 53 patients were prospectively questioned with a return rate of 75% (n = 40). 75 TSCC-patients were retrospectively questioned to increase numbers with a return rate of 55% (n = 41). All returned questionnaires (n = 106) were analyzed irrespective of completeness. The quantity of missing data for each question is given in the respective tables.3.2The patient characteristics of the TSCC- and H-patients are given in 3.3In total 37 of 81 (45.7%) TSCC-patients had HPV-DNA-positive tumors. Of the H-patients 7 of 25 (28.0%) had HPV-DNA-positive tonsillar tissues sample. In both disease entities and in the entire study population, (cancer and hyperplasia patients), patients with HPV-positive and HPV-negative tissue samples were not significantly different in age: In cancer patients with HPV-positive tumors the average age was 60.2 ± 9.4 yrs. The average age in the groups with HPV-negative tumors was 61.9 ± 9.1 yrs; Hyperplasia patients with HPV-positive tonsillar samples were on average 48.1 ± 13.4 yrs old versus 44.3 ± 11.9 yrs in the groups of patients with HPV-negative tonsillar samples. The entire population of patients with HPV-positive tonsillar tissue samples was on average 59.1 ± 10.3 yrs old and those with HPV-negative ones were on average 57.6 ± 12.3 yrs old; all p > 0.05. The effect of the social parameters on tonsillar HPV-DNA-status of the TSCC- and H- patients is shown in 4To the best of our knowledge the present study is the first prospective study with tissue typed HPV-status derived from TSCC as well as non-malignant tonsils correlating results with socioeconomic factors such as education, alcohol and tobacco intake, and sexual behavior.The results of this study cannot confirm a correlation between the presence of HPV-DNA in the examined tissue samples , n = 25) and the sexual behavior of the patients. However, despite the relatively small number of cases studied (n = 106), the well-established and highly significant correlation between smoking habit and HPV-status was confirmed. The HPV prevalence rate of all TSCC-cases was 45.7% (27/81). This was within the expected range for this northern German study population ,28,38.A statistically significant relationship between lifetime number of sexual partners/frequency of oral sex and HPV-status was not observed in this study when all cases are analyzed together nor when TSCC- and H-patients were considered separately. Although power was limited, analysis for trend showed, however, that amongst the H-patients tissue HPV-negativity was associated with higher lifetime number of sexual partners . SimilarWith a mean age of 45.2 years, H-patients were significantly younger than TSCC-patients (mean age: 61.1yrs), which might suggest a more liberal attitude towards sexual activity in H-patients than in older TSCC-patients. Despite the rather small H group (n = 25), it is worth noting see  that H-pThe detection of 7 HPV-positive cases among the 25 H cases was surprising. In previous studies, we have not detected HPV in clinically healthy mucosa or tonsils . This diIn the predominantly US-American literature , the corin-silico studies, the latter discrepancies are not fully taken into account when calculating odd ratios for the development of HPV16-associated HNSCC.However, HPV natural history studies related to the general population or MSM, and studies in HNSCC patients must be strictly separated . NaturalSyrjänen and co-workers ,31,32 haIn the present study, we investigated tissue samples derived from patients, whereas all natural history and some HNSCC studies are based on DNA extracted from gargle, brushes and oral rinses respectively. Since in the head and neck region precursor lesions as described for the cervix uteri (CIN I-III) have not been detected so far and since HPV analysis on clinically healthy mucosal sites of the head and neck remain HPV negative , the meaFurther questions that need be addressed to fully understand the natural history of HPV and, moreover, what it takes to transgress from HPV-DNA presence in the oral cavity to HPV-driven carcinogenesis include the following: Which e.g. immunologic factors influence incident oral HPV infections to become persistent? Why do people who practice intense and regular oral sex clear HPV infections more regularly and faster than people who have less oral sex? What are the reasons for the gender-specific differences in HPV uptake and clearance? Do patients with HPV16-related HNSCCs indeed arise from the small group of individuals who have acquired a persistent HPV16 infection through riskier sexual behavior at an earlier stage of their lives, even though HPV-prevalence and HPV-associated carcinogenesis are rare events even among people at highest risk (HIV-positive MSM)? Why isn't there a significantly higher incidence of tonsillar cancers among (HIV-positive) MSM, similar to that observed for anal cancer ? Why do With only n = 106 investigated patients, the main limitations of the present study are sample size and the differences in age of the patient populations studied. Therefore, the pooled estimate presented should be viewed with caution and considered exploratory only. The findings within the two cohorts are likely to be less confounded but have limited power. This is the first study in Germany or even Europe on HPV-infection of tonsillar tissue of head and neck cancer patients and patients with benign lesion that also examined sexual behavior. Therefore, data presented here can only be compared to results from outside Europe. In light of detected differences in HPV prevalence rates based solely on the geographical region where patients live, comparative analysis with other study populations is challenging. We did not correlate tissue HPV DNA infection with results derived from analysis of gargle or other sample material obtained from the same patients. Therefore, comparison of our results with results obtained in biomaterial other than tissue samples is not possible. A study focusing HPV DNA status in tissue, gargle and brush samples of the same patients is ongoing.In conclusion, in the present study no correlation between sexual behavior and HPV infection was found. The interpretation of HPV-related head and neck cancer as a STD should therefore be treated with caution. In the admittedly rather small group of H-patients, however, patients with HPV-negative tonsillar samples reported higher frequencies of practicing oral sex than patients with HPV-positive tissue samples. Overall, when communicating with patients and the public, it is important to ensure that patients with HPV-related head and neck cancer are not stigmatized. It is important to stress that HPV is widespread and HPV infections can occur in sexually active people without causing any disease. The epidemiological question of the level of risk associated with sexual activity or certain sexual activities is difficult to answer. Patient information should focus on the fact that these carcinomas have a better prognosis and not on the potential association with sexual activity. It seems important to acquire standardized high-quality risk factor data from patients originating from different geographical regions and from different study designs in order to advance our knowledge on the topic. Further studies are needed focusing on the mechanisms leading from persistent oral HPV infections to carcinogenesis.Elgar Susanne Quabius: Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Supervision, Writing - original draft, Writing - review & editing. Asita Fazel: Conceptualization, Data curation, Methodology, Validation. Christopher Knieling: Investigation. Stephan Gebhardt: Data curation, Investigation. Martin Laudien: Formal analysis, Methodology, Validation. Crystal Moore: Writing - review & editing. André Kühnel: Data curation, Investigation, Supervision. Florian Hoppe: Data curation, Investigation, Supervision. Robert Mlynski: Data curation, Supervision. Alessa Heinrichs: Investigation. Alexander Fabian: Data curation, Investigation. Markus Hoffmann: Conceptualization, Formal analysis, Methodology, Project administration, Supervision, Writing - original draft, Writing - review & editing.10.13039/501100005972Deutsche Krebshilfe, grant number 111777.The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The work was funded by the


To evaluate dentists’ readiness to assess the history of human papilloma virus (HPV) infections and recommend immunization among their patients.A link to a self-administered questionnaire was emailed to Ontario dentists. Dentists’ readiness and its determinants were assessed based on Transtheoretical Model’s ‘stages’ and ‘processes’ of change, respectively. Based on their current practices, dentists were either assigned to ‘pre-action’ or ‘action+’ stages.Of the 9,975 dentists contacted, 932 completed the survey; 51.9% participants were in action stage to assess the history of HPV infections and 20.5% to recommend immunization. Internationally-trained and those whose office’s physical layout was not a concern to discuss patients’ sexual history were more likely to assess the history. Dentists with higher knowledge about HPV vaccines, not concerned about the HPV vaccine safety, comfortable discussing sex-related topics with patients, or willing to exceed their scope of practice were more ready to recommend HPV immunization to their patients.Improving Ontario dentists’ knowledge and communication skills and changing their self-perceived role regarding HPV infections and vaccination can increase their capacity to minimize the burden of HPV infections. The incidence of oral cancers in high-income countries is shifting from oral cavity cancers generally attributable to tobacco consumption to oropharyngeal cancers (OPC) linked to human papillomavirus (HPV) oral infections . In CanaHPV infection is one of the most common sexually-transmitted infections, and it has been implicated as a cause of cancer for various anatomic sites including the cervix, vagina, vulva, penis, anus and oropharynx ,5. VertiIn recent decades, vaccines have been developed to prevent HPV infections and subsequent development of HPV-related cancers. Development of HPV-related OPC is associated with HPV types 16 and 18. While it is too early to identify the vaccine’s ability to lower the number of HPV-related OPC, randomized clinical trials have demonstrated the efficacy and safety of HPV vaccines ,11. In gDentists are poised to contribute significantly to both the uptake of the vaccine and completion rates . To imprUnderstanding the determinants of dentists’ readiness to assess HPV risk and recommend the HPV immunization is crucial for increasing the presence of dental professionals in HPV prevention. Daley and colleagues identified dentists’ knowledge of HPV and the HPV vaccine, their attitudes towards discussing HPV and its relation to sex, and the barriers dentists identified are keeping them from addressing HPV infections with their patients ,25. Our Accordingly, the objectives of this study were to determine Canadian dentists’ readiness to: assess patient’s HPV infection history; recommend HPV immunization; and explore associated determinants.Ethics approval was obtained for conducting this survey from the Research Ethics Board of Public Health Ontario (File number 2017–040.01). A statement was included in the survey questionnaire to record the active consent of participants. To further protect respondents’ privacy, sociodemographic groups with five or less respondents that could not be combined with another group, were dropped from the final analyses.The survey instrument was developed following a robust review of the literature. Based on relevancy to the study’s purpose, survey questions were framed using the Transtheoretical Model  and processes of change (POC)) . The surDentists’ readiness to assess HPV infection history/status and recommend HPV immunization and the associated determinats were assessed based on the TTM . TheoretAccording to the TTM, dentists indicating non-assessment of patient HPV infection history/status or not recommending immunization were placed in the ‘pre-action’ stage (precontemplation/ contemplation/ preparation), while those indicating assessing either all or some of their patients’ HPV infection history/status or recommending immunization were included in the ‘action +’ stage (action/ maintenance). Determinants of dentists’ readiness to act in each of the abovementioned categories included demographics, subject knowledge , and other items derived from POC . These iFirstly, descriptive analyses were performed: assessed the proportions of respondents as per their socio-demographic characteristics; calculated proportions who were in pre-action or action+ stage for assessing HPV risk and immunization; calculated median overall knowledge score (14 out of 20) and also specific knowledge scores of OPC (2 out of 4), HPV infections (9 out of 10), and HPV immunization (3 out of 6), dichotomized proportion of respondents based on median knowledges scores, and examined their distributions into pre-action or action+ stage; and assessed propotions of agreed or not agreed to statements based on POC and accordingly if they were in pre-action or action+ stage.Secondly, binary logistic regression analyses were performed to assess the association between each determinant and dentists’ readiness (pre-action vs. action+) to take HPV infection history/status and recommend HPV immunization. Lastly, multivaraible logistic regression models were developed that included only the statistically significant variables (p<0.05) emerging from the simple binary logistic regression models. As 93.13% of the participants reported complete data, all estimates are based on complete-case analyses. The distributions of missing data are reported in Of the 9,975 dentists contacted, 932 dentists completed the survey . Approximately 52% of respondents were in the action stage for assessing patient HPV- history/status, but only 20.5% of respondents recommend HPV-immunization to patients . Fig 1A Statistically significant socio-demographic predictors of dentists’ readiness to assess patient HPV-related history/status include place of training, primary setting of occupation, and years practicing in Canada . When coIn terms of knowledge, dentists whose OPC knowledge scores were equal to or above the median value were more likely  to assess the history of HPV infections than their counterparts. Statements developed using POC show that dentists who are comfortable with patients of opposite sex and minors, and in discussing sexual history, find dental appointments time adequate, do not worry about confidentiality, perceive assessing HPV history to be in their scope of practice, and do not find their dental office layout as a barrier for such discussions are statistically significantly more in action+ stage than their counterparts.Statistically significant socio-demographic predictors of dentists’ readiness to recommend HPV vaccine include age, primary setting of occupation, and practice type . Older dIn terms of knowledge, dentists scoring equal to or above the median overall knowledge score  and HPV immunization knowledge score  were more likely to recommend immunization to their patients than their counterparts. Statements based on POC show that dentists who are not concerned about the HPV vaccine safety or liability issues, believe that it is their role to recommend immunization, find dental appointments time adequate, and comfortable discussing sexual history with patients are statistically significantly more in action+ stage than their counterparts.Place of training, OPC knowledge, and perceiving the physical layout of the clinic as a barrier to assess sexual history remained significant predictors for dentists’ readiness to assess the history of HPV infections . InternaDentist’s age, HPV vaccine knowledge score, and agreement with statements derived from the POC remained significant predictors for readiness to recommend HPV immunization . DentistThe objectives of this paper were to assess dentists’ readiness to assess the history of patient HPV infections/status and willingness to recommend HPV immunization, and to explore the readiness-associated determinants. Our findings reveal low proportions of dentists in both outcomes, with dentists’ readiness to assess patient HPV history/status higher than their readiness to recommend HPV immunization. However, a comparison of current study findings to earlier findings with Florida dentists, point to an even lower proportion of Florida dentists who were recommending HPV immunization to their female patients . This diDentists’ readiness to assess HPV infection history and status was predicted by place of training, OPC knowledge, and the physical layout of the clinic. The existing literature does not fully explain the difference in readiness to assess history of HPV infections between the Canadian and internationally trained dentists. One possible explanation is that internationally trained dentists are less influenced by the self-perceived barriers because of utilizing more diverse communication techniques . AlternaIn addition to place of training, dentists’ readiness to assess history of HPV infections was also predicted by OPC knowledge, but not HPV infection knowledge. This is understandable as it is expected that educational interventions for dentists would focus primarily on oral implications of HPV infections including OPC. In addition, this finding highlights the importance of more educational interventions to increase OPC related knowledge. Additionally, dentists’ readiness to assess patient history of HPV infection was predicted by whether dentists’ view the physical layout of the clinic as a reason for not assessing the history of HPV infections. This concern was also indicated by a group of dentists and dental hygienists in a mixed-method study ; particiFor dentists’ readiness to recommend HPV immunization, among all socio-demographic characteristics, age was the only factor that was positively associated. This finding is consistent with what Hosking et al. (2017) reported when they surveyed a sample of Pediatric Dentistry Graduate Program Directors in the U.S. The increased age among the Program Directors was positively correlated with recommending HPV immunization to patients . The reaIn addition to age, dentists’ HPV vaccine knowledge and concerns about the vaccine safety, discussing sex-related topics, and exceeding the scope of practice were significant predictors of dentists’ readiness to recommend HPV immunization. These findings add to the current understanding how dentists’ readiness to recommend HPV is shaped across the SOC. Daley et al (2014) identified that absence of concerns about liability issues is associated with occupying the contemplation stage rather than the pre-contemplation stage while our study suggests that absence of concerns about liability issues does not predict occupying the action+ stage . Daley eSignificant predictors identified in this study were derived from four different POC; consciousness raising, dramatic relief, self-reevaluation, and stimulus control. These four processes represent different cognitive and behavioral activities that individuals perform to move between the stages. Consciousness raising and dramatic relief usually mediate transition from pre-contemplation to contemplation. Self-reevaluation often mediates transition from contemplation to preparation, while stimulus control is proposed to mediate transition from action to maintenance . Our resDespite the facts that we utilized a theory-informed approach to answer critical research questions, no formal tests have been performed to assess the validity and reliability of the survey instrument. Accordingly, this study should be interpreted as an exploratory study that highlights potential areas for future intervention. The cross-sectional design of our study did not allow us to confirm the mediation effects of the POC. It is possible that these processes were activated after progressing to a given stage. Therefore, caution must be exercised when designing professional interventions to shift dentists to the action+ stage. Moreover, our study did not evaluate all POC due to the length of the survey. Including all the POC and other TTM constructs may change the estimates and/or reveal new predictors. Furthermore, our study dichotomized the SOC into pre-action and action+ stages, which may not directly reveal how dentists move from one particular stage to another stage.In terms of the generalizability of the study findings to Ontario dentists, the low participation rate in the study may limit the generalizability of the results to Ontario dentists who are similar to the study sample. Although our communication with the RCSO indicates that the characteristics of the study sample is comparable to the characteristics of the registered Ontario dentists in term of age, sex, and training country (data not shown), it is expected that those who participated in the study are those who are currently in the action+, which may overestimate Ontario dentists’ readiness to assess the history of HPV infections and recommend HPV immunization and underestimate the effects of the examined determinants on their readiness .Although this study demonstrated that dentists have the potential to play key roles in the prevention of HPV infections, collaboration between different stakeholders can improve dentist’s readiness to assess the history of HPV infections and recommend HPV immunization. Academic institutions need to enrich their curricula with more information about OPC, HPV immunization and how to communicate such sensitive issues with patients. Regulatory colleges also need to promote developing HPV related content for continuing dental education courses. Professional dental organizations can address dentists’ discomfort and concerns about patients’ privacy by adding items about HPV infections and immunization to the medical history forms. More importantly, the role of dentists in the prevention of HPV infections, including their role in the risk assessment of OPC, and recommending immunization needs to be more clearly defined . FurtherThis study shows the minimal contribution dentists are making to the prevention of HPV infection. Also demonstrated is the larger role dentists can play in reducing HPV infection and its sequel. Dentists’ lack knowledge in the areas of HPV-related OPC and available HPV vaccines, including safety and efficacy. Other determinants for dentists’ readiness include patient privacy, discussion of sensitive topic, and dangers of exceeding their scope of practice. Future research should explore the role of the other POC and Transtheoretical Model constructs and patient-related factors in dentists’ readiness to engage in HPV prevention behaviors. Development of educational interventions to ameliorate dentists perceived barriers to HPV screening are also needed.S1 File(DOCX)Click here for additional data file.S2 File(DOCX)Click here for additional data file.


Classes were randomized to receive one of two cancer prevention programs  or healthy weight (control)). Both programs contained eight technology-mediated sessions, including weekly emails and private Facebook group posts. Participants completed pre-/post-test surveys and submitted weekly qualitative reflections. Data were analyzed using descriptive statistics and thematic review for qualitative data. Knowledge improved among participants in the HPV vaccination intervention relative to those in the control condition. Participants (97%) interacted on Facebook by “liking” a post or comment or posting a comment. Participants demonstrated robust engagement and high treatment satisfaction. Results suggests that social media is an effective platform to reach college students with health promotion interventions and increase HPV vaccination awareness in this important catch-up population.College-aged women and men are an important catch-up population for human papillomavirus (HPV) vaccination interventions. Limited research has explored technology-mediated HPV vaccination awareness interventions aimed at college students. The purpose was to evaluate a novel, technology-mediated, social media-based intervention to promote HPV vaccination among college students. A controlled, quasi-experimental, mixed methods study examined the feasibility of a technology-based intervention among two undergraduate classes ( Human papillomavirus (HPV) is pervasive and almost all men and women will contract it at some point in their lifetime . HPV is ®9, prevents up to 90% of HPV-related cancers  layout, it is hard to make a post really stand out.” Participants appreciated fun and interactive elements of the intervention, such as polls. Participants also commented that Facebook encouraged interaction. According to one participant, “I really enjoyed conversing and sharing opinions with peers via a social network. I felt more inclined to share more personal information because it was online versus a face-to-face conversation.”Based on the open-ended weekly reflections, Facebook emerged as an acceptable platform for the intervention see . StudentWe also monitored level of engagement with the Facebook HPV intervention content see . These dTo our knowledge, this is the first study to deliver an HPV vaccination awareness intervention through Facebook and electronic newsletters to college students. This technology-mediated, theory-based HPV vaccination awareness intervention was well accepted by participants. Findings suggest the approach was effective in improving knowledge about HPV and HPV vaccination. Participants reported that the intervention addressed gaps in knowledge related to men’s susceptibility to HPV and the link between HPV and oral cancer, which have been shown in previous studies to be important gaps limiting HPV vaccination . ParticiAt the conclusion of the HPV intervention, the number of participants initiating/completing the vaccination series increased, as did the number of young adults indicating they intended to get vaccinated in the next 6 months. The change in vaccination coverage was modest over this 9-week period and did not differ statistically from the control group in this small feasibility study. However, the demonstrated increase in knowledge about HPV and vaccination coupled with the suggestion of a shift in intensions to get vaccinated suggests that the intervention offers a promising approach to target the catch-up population and achieve the ambitious Healthy People 2020 80% full coverage goal.Participants’ intervention engagement and treatment satisfaction suggest that this approach offers utility and scalability among college students. The electronic newsletter showed high penetration with approximately 90% of participants opening the email each week. Almost all participants interacted on Facebook by “liking” a post or comment or posting a comment. An average of more than four comments or likes were made per person each week throughout the intervention . ParticiAlthough HPV vaccination is effective, low coverage remains a challenge for public health professionals. College students represent an important catch-up population who are at increased risk of acquiring HPV. This technology-mediated intervention supports research that social media serves as an appropriate platform to improve awareness and vaccination coverage . InterveFindings should be understood within the context of the study’s limitations. The small sample size and homogeneity of the population limit the generalizability of the results. The relatively short intervention and lack of extended follow-up to confirm receipt of HPV vaccinations are limitations of this study. Additionally, the relatively high baseline rate of full vaccination left modest room to increase vaccination rates. Finally, there is a risk of contamination between conditions because students were registered in two sections of the same course, with the same professor, at the same university and both interventions were described in the informed consent document.This pilot study offers a number of strengths that demonstrate potential for scalability and dissemination of this intervention approach. In one of the first HPV vaccination awareness interventions for college students delivered through electronic newsletters and Facebook, participants demonstrated robust engagement and high treatment satisfaction. Moreover, the study was randomized and controlled, with a high retention rate. Additional study strengths include the use of objective measures and qualitative open-ended assessment of intervention engagement. Finally, the automated delivery of electronic newsletters and Facebook posts represents an opportunity to replicate the intervention with limited time and opportunity cost.A technology-mediated HPV vaccination awareness intervention increased college students’ knowledge of HPV and HPV vaccination. Objective measures and qualitative open-ended assessment of the intervention showed high levels of engagement with the electronic newsletters and Facebook group. The effectiveness of this pilot study suggests that social media is an appropriate platform to reach college students with health promotion interventions and increase HPV vaccination awareness in this important catch-up population.


Bladder cancer is one of the leading causes of cancer death in adults worldwide. There are various risk factors described for the bladder cancer development including genetic background as well as environmental exposure. Currently, infectious agents such as human papilloma virus (HPV) has also been linked to bladder cancer risk. The current study aimed to evaluate the potential correlation between HPV infection and the oncological outcome in urothelial bladder cancer.Totally 106 tissue samples of histopathologically confirmed transitional cell carcinoma (TCC) of the urinary bladder were included in this study. The presence of high risk (types 16 and 18) and low risk (types 11 and 6) types of HPV was evaluated using polymerase chain reaction (PCR) followed by in situ hybridization.P = 0.015). Moreover, our findings showed a significant relation between infection with HPV and tumor stage, tumor grade, muscle invasion of the tumor, as well as tumor recurrence. The results of Chi-square Test indicated that there is significant statistical association between types of HPV and tumor grade .Out of 106 bladder cancer patients, a total of 24 cases (22.6%) were positive HPV infection. The most common type of HPV detected was type 16 followed by types 11 and 18, and 6. According to independent T-test results, there was a significant association between mean age and HPV infection (Our findings indicated that a family history of cancer and HPV infection can be potential independent predictive factors for tumor recurrence in bladder cancer. Overall, the results of this study strongly indicate a significant relationship between HPV infection and an aggravated outcome of the disease and a higher risk of recurrence in patients with bladder cancer. Bladder cancer is one of the leading causes of cancer death in adults worldwide and approximately 400,000 new cases and 186,000 deaths annually has been reported globally . TransitAt present, avoiding risk factors is the only way to prevent bladder cancer and the treatments are invasive and costly . Thus, aIn the present study, we have evaluated the presence of high risk (types 16 and 18) and low risk (types 6 and 11) HPV types in bladder tumors and the possible correlation between HPV infection and oncological outcomes of the disease.A total of 106 formalin fixed-paraffin embedded (FFPE) tissue samples from patients with histopathologically confirmed TCC of the urinary bladder were enrolled in this study. A self-administered questionnaire for clinicopathologic characteristics and demographic data was completed by the patients. Grading and staging were carried out according to the American Joint Committee on Cancer’s 2002 TNM staging system and World Health Organization (WHO) respectively. Individuals with the history of other malignancies and/or cancer metastasized to bladder from another origin were excluded. This study was approved by the institutional Ethics Committee.Genomic DNA was extracted from tissue samples by QIAamp DNA FFPE Tissue kit  according to the manufacturer’s guideline. The tissue samples subjected to the amplification of a highly conserved late region I (L1) of HPV genome by PCR assay using consensus primer pairs  to detect all recognized HPV types, as described previously . The ampIn this study, descriptive statistics  and inferential statistical tests , Chi-square and Fisher’s exact test) were used.The relationship between tumor grade, tumor stage, as well as recurrence after 18 month, and smoking status, family history of cancer, and HPV infection was assessed using crude and age-sex adjusted of odds ratio and their 95% confidence intervals by logistic and penalized logistic regression. All analysis performed by STATA software ver. 13.Categorical variables and their distributions in each group was compared by chi-squared or Fisher’s exact test and continuous variable (age) was compared using independent t-test.P = 0.015). The association between patient characteristics and HPV status were presented in Table In the present study, out of 106 bladder cancer patients examined, a total of 24 cases (22.6%) were positive HPV infection. The most common type of HPV detected was type 16 with a frequency of 10 (9.4%); followed by types 11 and 18, and 6 with frequencies of 5.7, 5.7, and 0.9%, respectively. The mean age of the subjects was 62.98 ± 10.26 years (rang from 38 to 89 years). The mean age of patients infected with HPV was 58.54 ± 11.39 years. The mean age of patients who were negative for HPV infection was 64.28 ± 9.59 years. According to independent T-test results, there was a significant association between mean age and HPV infection (P = 0.005) and recurrence after 18 month (P = 0.015). Significant statistical association was also observed between family history of cancer and tumor grade (P = 0.042), muscle invasion (P = 0.018), and recurrence after 18 month (P < 0.001).Table P = 0.044). However, there were no significant statistical association between sex, tumor stage, muscle invasion, and recurrence after 18 month (P > 0.05). We investigated the relationship between recurrence after 18 month with demographic and prognostic factors of bladder cancer patients using univariate and multivariate analysis . Moreover, there was a significant relation between HPV infection and recurrence within 18 months. The odds ratio of recurrence in patients with HPV infection is approximately 7 times more than those without HPV infection (p = 0.008). According to the univariate analysis results, a statistically significant relationship between recurrence and T3-T4 tumor stage compared to T0 tumor stage has been reported (p = 0.015). However, in multivariate analysis after considering the effect of other variables affecting recurrence, there was no significant relationship between recurrence and muscle invasion (p = 0.478).The association between types of HPV and sex, tumor grade, tumor stage, muscle invasion, and recurrence after 18 month has been presented in Table Involvement of HPV in several kinds of cancers, including cervical, oropharyngeal, and anal cancers, have been reported in earlier studies . HPV infIt has been determined that the prevalence of HPV varies among different populations and geographical regions. Furthermore, diagnostic methods used in the detection of the virus affect the rates reported for its prevalence . AnotherAll HPV positive samples in the present study were infected with a single type of the virus, and infection with multiple types was not observed. This result is not in agreement with the findings of an earlier study which has detected different types of HPV simultaneously in the sample and has stated that simultaneous infection with several types of HPV virus may increase the risk of carcinogenesis .Even though the rate of bladder cancer is higher in men than in women , the resIn earlier studies, a significant relationship was established between cigarette smoking and the risk of bladder cancer , but theThe relationship between HPV infection and bladder cancer has been addressed in several previous studies , 26. A sIn general, the importance of HPV infection as a prognostic factor for the survival of urological cancer patients has been assessed in other studies , 28. SevIt has been shown that most of bladder tumors recur within 12 months of treatment . The encPreliminary analysis of our data showed that HPV infection had an association with age, and the mean age of the HPV-positive individuals was 6 years less than those patients in which HPV was not diagnosed. This result is in agreement with the findings of a previous study . As HPV Previous studies have shown that there is a relationship between the grade of the bladder tumor and age and also that a higher rate of low-grade tumors is observed in the older ages , but no In our study, a family history of cancer had an association with the grade of the tumor, muscle invasion, and tumor recurrence. Furthermore results of the multivariant analysis, after the adjustment of the variables, showed a significant relationship between the variables of family history and HPV infection with tumor recurrence within 18 months, while any significant relationships between the grade and stage and muscle invasion of the tumor and tumor recurrence rate was found. Thus, it can be concluded that a family history of cancer and HPV infection can be potential independent predictive factors for tumor recurrence in bladder cancer. Overall, the results of this study strongly indicate a significant relationship between HPV infection and an aggravated outcome of the disease and a higher risk of recurrence in patients with bladder cancer.However, no study is without limitations. Our data was collected from only one center and although we included more than 100 cases, it is not a multi-center study. Secondly, the samples were in FFPE form and were not fresh frozen tissue (FFT). Quality of PCR might be slightly higher in FFT samples compared to FFPE; however, the difference is trivial and non-significant in many cases , 36. ForBladder cancer, especially its muscle invasive form has a poor prognosis and high probability of recurrence, and studies have shown a mean survival rate of about 28 months for the patients who experience bladder cancer recurrence . There i


Background: Since 2007, all Canadian provinces and territories have had a publicly funded program for vaccination against human papillomavirus (HPV) infection. The objective of this study was to describe the evolution of these vaccination programs. Methods: This was a targeted literature review of public HPV vaccination programs and vaccination coverage rates, based on information provided by jurisdictional public health authorities. Results: HPV vaccination of schoolgirls began in school years 2007/08 to 2010/11 with three doses of the quadrivalent HPV vaccine in all provinces except Quebec, which started with two doses. By 2018/19, all jurisdictions were vaccinating with two doses of the nonavalent vaccine in both girls and boys, except Quebec, which used a mixed vaccination schedule with one dose of the nonavalent and one dose of the bivalent vaccines. Public HPV vaccination programs in most provinces include after-school catch-up vaccination. Immunocompromised or other high-risk individuals are eligible for the HPV public vaccination program in most provinces, but policies vary by jurisdiction. In 2017/18, vaccination coverage rates in provincial HPV school-based programs varied from 62% in Ontario to 86% in Prince Edward Island in girls and from 58% in Ontario to 86% in Prince Edward Island in boys. Conclusions: Since their introduction, Canadian school-based HPV public vaccination programs have evolved from a three-dose to a two-dose schedule, from a quadrivalent to a nonavalent vaccine, and from a girls-only to a gender-neutral policy. Vaccination coverage rates have varied markedly and only Prince Edward Island and Newfoundland/Labrador have maintained rates exceeding 80%. Human papillomavirus (HPV) is a sexually transmitted infection , with moCanada was one of the first countries to implement a publicly funded HPV vaccination program. Three vaccines to protect against carcinogenic strains of HPV have been licensed in Canada ,6. FirstThis was a targeted literature review of HPV vaccination programs in Canada, focused on governmental databases and statistics, informal reports, Embase, and PubMed. The scope of the searches was based on the PICO (+) framework  described in We retrieved information by province/territory on the publicly funded, school-based primary grade(s) covered for vaccination, temporary catch-up cohorts, if the programs covered girls and boys, year of program introduction, vaccination schedule, and vaccine coverage rate by year and sex, where published and available. Birth year of children eligible for school-based vaccination programs and other groups eligible for public HPV vaccination programs was also extracted when available. Program details were synthesized by province/territory and year, including vaccination schedule and vaccination coverage rate by sex, and are presented together over time.All available vaccine coverage rate data were extracted; however, this paper only presents vaccine coverage rates for cohorts that received the full course of HPV vaccination based on the recommended dose regimen at the time of administration.When not available, birth year of children eligible for school-based vaccination programs was calculated using the assumption that children are five years old when they start kindergarten. For example, if girls and boys are eligible for vaccination in Grade 6 for the 2017/18 school year, it was assumed that they were 11 years old when they were eligible for the first dose of HPV vaccine and it was calculated that the birth year of this cohort was 2006 (2017–11).Vaccination coverage rate (as a percentage) is expressed as the number of children vaccinated relative to the number eligible for vaccination.This was a review of publicly available aggregate data and information from published literature; therefore, ethical approval was not required.As shown in In 2013/14, Prince Edward Island was the first province to include boys in the school-based vaccination program. Alberta followed in 2014/15 and Nova Scotia in 2015/16 . All othAs shown in In addition to the school-based programs, in most of the jurisdictions, individuals who missed the full course while at school remained eligible, as shown in Time trends in HPV vaccination coverage rates (full course) in schoolgirls from 2007/08 to 2018/19 are shown in The most recent HPV vaccination coverage rates  in school children are shown in Since their introduction in 2007, Canadian publicly funded HPV vaccination programs have evolved generally from a three-dose to a two-dose schedule, from a quadrivalent to a nonavalent vaccine, and from a girls-only to a gender-neutral program. HPV programs have been shown to be effective, resulting in decline in the incidence of pre-cancerous cervical lesions and genital warts in Canada .In addition to the school-based programs, in most jurisdictions, individuals who missed the full course while at school remained eligible for a certain period of time to receive publicly funded HPV vaccine. Research has shown that providing opportunities to receive missed doses in schools through catch-up programs is important in optimizing coverage .Most jurisdictions have enhanced their public HPV vaccination programs to include high-risk groups, such as men who have sex with men, transsexual persons, HIV-infected individuals, and other at-risk groups. However, there is no standardization and programs vary across provinces and territories.The transition to a mixed HPV vaccine dose schedule in Quebec in the fall of 2018 has been widely debated, stemming from the limited clinical efficacy data of this schedule before adoption ,42,43,44The current COVID-19 pandemic has disrupted many immunization activities across Canada. School closings, originated from the need to control viral transmission, and disruptions from competing priorities in the capacity of the public health system have led to a decrease in coverage in the school-based programs. Provincial surveillance mechanisms are currently assessing the extent of the vaccination delays and losses in coverage .Despite the challenges imposed by its large land area (the second largest country in the world), sparsely populated rural areas, and lack of a central coordinating authority for overseeing immunization delivery, Canadian HPV vaccination programs have largely succeeded, relative to other high-income countries. However, current vaccine coverage rates fall short of the Canadian Partnership Against Cancer (CPAC)’s target to eliminate cervical cancer by 2040. CPAC’s recommendations include attaining: 90% of 17-year-olds to be fully vaccinated by 2025; 90% of eligible women to have been screened with an HPV test by 2030; and 90% of all women with an abnormal screening result to receive within 3 months appropriate diagnostic and treatment by 2030 .Vaccination coverage rates have varied markedly by jurisdiction, and there have been no consistent time trends. Irrespective of jurisdiction, coverage rates in schoolboys have been similar to those in schoolgirls. Since the 2012/13 school year, only Nova Scotia, Prince Edward Island, and Newfoundland/Labrador have had vaccination coverage rates exceeding 80% in any school year. The recommendations of the Canadian Immunization Committee, that 80% of eligible schoolgirls receive the required doses of HPV vaccine within 2 years and 90% within 5 years of program introduction, have largely not been met . More reProvinces with the same vaccination program evolution—e.g., Saskatchewan, Ontario, New Brunswick, and Prince Edward Island—have widely different coverage rates. There is no clear evidence that a change in the number of doses was associated with changes in vaccination coverage. There are eight jurisdictions that switched from a three-dose to a two-dose strategy and in only two of them was there a more than five percent increase in vaccination coverage: Saskatchewan and Nova Scotia, both in 2014/2015 to 2016/2017. Similarly, switching the vaccine (but maintaining the same number of doses) had no apparent effect on vaccination coverage. There were six instances of switching the vaccine while maintaining a two-dose schedule and in no instance was there a change in vaccination coverage of ≥ 5%.Gilbert et al. (2016) explored determinants of HPV non-vaccination and vaccine refusal in girls 12–14 years old, based on data from the Childhood National Immunization Coverage Survey of 2013 . Among sA 2014 study of a nationally representative sample of Canadian parents of boys aged 9–16 examined psychosocial factors in parents’ HPV vaccine decision-making for their son ,51. GrouMore recently, Tatar et al. (2019) examined parental HPV vaccine hesitancy from a nationally representative sample of Canadian parents of 9–16 years old boys and girls in 2016 and 2017 . HPV-relVaccine coverage rates and type of service delivery model may also be impacted by the diverse geography and contextual means of delivery across the Canadian landscape. In Calgary, Alberta, during the period 2008–11, the HPV vaccine was offered free of charge to all girls in Grades 5 and 9, with two different service delivery models, depending upon the acceptance of the program by the local school board—immunization against HPV was not permitted in-school in the Calgary Catholic School District and at a small number of private schools, and in these cases, vaccination was provided in the community at Public Health Clinics . HPV vacBird et al. (2017) reported a meta-analysis of vaccine uptake rates in six of the Canadian provinces based on 12 studies published in the period 2010–2016 . Rates oMany countries in Europe and the Americas included HPV vaccination of adolescents in their national immunization programs, beginning in 2007 . These pThe present study is limited in that there are gaps in the available information. Not all HPV vaccine coverage rates have been reported for all years, age, and sex by each jurisdiction in Canada. Coverage in other eligible groups outside school-based is rarely available. Canada does not have a national vaccination surveillance program; therefore, there is a lack of standardized methodologies for reporting vaccination coverage rates across jurisdictions, making it difficult to compare vaccination rates ,59. We rIn conclusion, since their implementation in schoolgirls in 2007, provincial and territorial programs have undergone multiple policy changes, gradually increasing population protection via inclusion of boys and high-risk groups. Over time, policy changes have reflected the evolving science of HPV vaccination and funding support. While there are methodological variations across jurisdictions in how data are collected and reported, HPV vaccination rate targets clearly remain to be met in the school-based public programs in Canada. The data collated in this report may assist Canadian health authorities in addressing the shortfall in HPV vaccination coverage, with the eventual goal of eliminating HPV-related cervical and other cancers.


Population-specific epidemiologic data on human Papillomavirus infection, which are limited in most of the SubSaharan African countries, are necessary for effective cervical cancer prevention. This study aimed to generate population-specific data on human Papillomavirus infections, and determine which of these, self-collected and provider-collected specimens, gives a higher estimate of the prevalence of human Papillomaviruses, including vaccine and non-vaccine-type human Papillomavirus.  In this cross-sectional study, following a questionnaire-based collection of epidemiological data, self-, and provider-collected specimens, obtained from women 15−65 years of age, were analysed for human Papillomavirus types by a nested-multiplex polymerase chain reaction, and for cervical lesions by Pap testing. HPV data were categorised according to risk type and vaccine types for further analysis. p ≤ 0.001). The prevalence of quadrivalent vaccine-type human Papillomaviruses was 12.3% with self-collected specimens, but 6.0% with provider-collected specimens. For the nonavalent vaccine-types, the prevalences were 26.6% and 16.7% respectively. There were multiple infections involving both vaccine-preventable and nonvaccine preventable high-risk human Papillomavirus genotypes.  The difference between the overall human Papillomavirus infection prevalences obtained with the self-collected specimens, 43.1% (95% CI of 38.0–51.0%) and that with the provider-collected samples, 23.3% (95% CI of 19.0–31.0%) were significant ( The Akuse subdistrict can, therefore, be said to have a high burden of human Papillomavirus infections, which included nonvaccine types, as detected with both self-collected and provider-collected specimens. These imply that self-collection is to be given a higher consideration as a means for a population-based high-risk human Papillomavirus infections burdens assessment/screening. Additionally, even with a successful implementation of the HPV vaccination, if introduced in Ghana, there is still the need to continue with the screening of women. Of over 200 genotypes of the ubiquitous human Papillomaviruses (HPVs), about 50 are known to infect the mucosal epithelia of the following parts of the human body; cervix, vagina, vulva, penis, anus, and the oropharynx –3, oftenThe epidemiologic data on the human Papillomavirus infection, and related cancers and precancers have been shown to vary between geographical areas of the world  and to bHowever, among over 6.5 million women are at risk of cervical cancer in Ghana, data on the prevalence of HPV both in the general population and among women with all grades of cervical lesions are limited. Additionally, in spite of its indicated advantages –17, therThe few hospital-based studies (which used provider-collected specimens) in Ghana, have reported varying prevalences of HPV infections among different groups of women diagnosed with different stages of cancers and precancers. These include prevalences of 10.7% among women who reported for cervical cancer screening at a tertiary hospital ; 98.0% , 89.8%  all amonTherefore, both collection methods were employed in this study with the aim of generating baseline, population-based prevaccination HPV infection and cervical lesions prevalences of a purported high-risk community. Specifically, the aim was to estimate the proportions of the overall HPV infections burden that are due to high-risk HPV infections which may or may not be prevented by the available bivalent, quadrivalent, and nonavalent HPV vaccines.The data presented herein was part of the findings of a larger cross-sectional study, for which most of the methods presented herein have been previously published , 26.S) since the population was less than 10000. The expected HPV prevalence (p) and the degree of accuracy (d) used were 26.3% and 0.065 respectively (these were based on studies in the neighbouring West African countries), Furthermore, being a cross-sectional study, a design factor of 1.2% was applied and then based on literature, an estimated response rate to cervical screening of 60% was accounted for. The sample size of a minimum of 352 women for the study was thus obtained. The number of women recruited from each community was distributed by probability proportional to the size of the communities.The Lower Manya Krobo District was selected for this study because it has consistently (since 2010) been the district with the highest prevalence of sexually transmitted infection (STI) in Ghana, and therefore considered a high-risk location for HPV infections. Using random selection, the Akuse subdistrict, which was made up of 18 communities, (centred at the coordinates 6″06′02.43N and 0″7′16.87E) was selected from among the five sub-districts. At the time of the study, the estimated population of women between the ages of 15 and 64 years, was 2595, out of the total multiethnic population of 8887 persons. The sample size for the study was determined with the random sample size equations and a modification  consented and completed the study questionnaire. Although they were all invited for the collection of specimens, either at the Akuse Government Hospital or at a specified location within their communities , a totalThe study was approved by the Ethics Review Board of the Ghana Health Service (ID No GHS-ERC: 06/11/10). Informed consent, and parental consent and child assent (between 15 and 18 years of age) were obtained from or/and for the participants (as it applied) after explaining the main research goals, sample collection procedures, potential benefits and harms, and privacy and confidentiality of data collected.The methods used for the collection of the specimens were as previously reported by Awua et al. . SpecifiμL of DNAgard®Tissue  in a 2 mL screw-capped microcentrifuge tube and the head of the wooden spatula was broken and added to the same 2 mL screw-capped tube to complete the sample used for HPV testing. These specimens were designated as Provider-Collected (PC) specimens. All specimens for HPV testing were transported at 4°C and store at −20°C until used for HPV testing.Thereafter, a health personnel then performed a standardized vagina examination and, with the aid of a sterile plastic disposable speculum, and the PAP-PAK® Cytology kit  collected cervical specimens according to the manufacturer's instructions, for Papanicolaou (Pap) smear and HPV testing. Briefly, the head of a wooden Ayre's spatula was used to collect cellular material from the cervix and the squamocolumnar junction, and then a cytobrush was used to collect cellular material from the endocervix. Each of these was smeared uniformly on separate sections of a microscopic slide (for Pap testing). Thereafter, a fixative (95% ethanol and 5% polyethylene glycol), provided with the kit, was applied. The cytobrush was then rinsed in 50 The slides were completely immersed in two changes of 95% ethanol, overnight. Thereafter, they were rinsed with a continuous flow of running water for 5 minutes and then stained with Mayer's Hematoxylin for 5 minutes. The slides were washed in running water for 5 minutes, after which they were dehydrated by immersion in 95% ethanol for 2 minutes. These were passed through Orange G-6 for 2 minutes, followed by two rinses with 95% ethanol, each time for 10 seconds. The slides were then transferred into a solution of EA for 3 minutes and rinsed very well with two changes of 95% ethanol, each time for 10 seconds. Dehydration was completed in absolute ethanol for 1 minute. The slides were air-dried on the bench, cleared in xylene and coverslip fixed with DPX mountant . The slides were then examined for cellular characteristics by two cytotechnologists using an Olympus BX51TF microscope with an Olympus DP20 camera . The slides for which there was no consensus between the two cytotechnologists, a cytopathologist examined the slides. Additionally, the cytopathologist examined all slides reported as unsatisfactory and also, 10% of the slides for which there was a consensus between the cytotechnologists. Included in the slides for examination were previously confirmed slides that were positive and negative for cervical lesions.µL of each specimen (SC and PC) on the MagNA Pure LC automated system , using the MagNA Pure DNA Extraction Kit  according to the manufactures specification, but with the following modification; which was the addition of 15 µL of RNase to the lysis buffer per specimen. The negative controls included for each set of extraction were PBS, DNase/RNase free water, and DNAGard, while the positive control was a suspension of HeLa cells with an integrated HPV 18 genome. The specimen/DNA quality was assessed by real-time PCR amplification of the housekeeping gene, RNase H was added in 10 µL of the DNA extract and analysed with a Light Cycler 480 and related software .The DNA extraction method described herein was followed as previously described by Awua et al. . SpecifiµL of bacteriophage T7 gene6 exonuclease  that removed the non-labelled strand after 40 minutes incubation at room temperature. The single-stranded HPV DNA were incubated for hybridization at 60°C for 10 minutes. Streptavidin-phycoerythrin (PE) (Invitrogen) in 1-tetramethyl ammonium chloride (TMAC) (Sigma), was subsequently added and incubated for 5 minutes at 60°C. Genotype specific hybridizations were detected on a Luminex Liquid Chip 200 flow cytometer (Qiagen) using the Luminex IS software (Luminex).The extracted DNA were amplified by nested PCR reactions using PGMY09/PGMY11 and GP5+/GP6+ primers, as previously described by Zubach et al.  and AwuaFrequencies, proportions or/and 95% CI of the proportions were used to describe the distributions and summarize data on specimens collected, HPV genotypes detected, HPV infections, high-risk types of infections, low risk types of infections, and vaccine-type HPVs infections . Chi-square analysis was used to determine the statistical significance of the differences in the overall HPV, high-risk HPVs  and low-risk HPVs  prevalences between the two collection methods. The Cohen's Kappa analysis was used to determine the extent of agreement between the HPV infections determined with self-collected specimens and those with provider-collected specimens. The McNemar's test was used to determine the statistical significance of the differences between the concordances in the detection of any HPV infection  and high-risk HPV infection using specimens collected by each of the two methods. The associations between the sexual characteristics and HPV positivity for each of the HPV infection categories  were obtained by logistic regression.Of the 473 women invited to participate in this study, 415 (87.7%) agreed to and completed the study questionnaire. A total of 253 (60.96%) of 415 women who consented to participate in the study provided specimens. Tables The quality of each of the 477 specimens obtained from the 253 women who provided specimens for this study was tested by real-time PCR amplification for the housekeeping gene, RNase H. Although 17 of the 244 self-collected and 6 of the 233 provider-collected specimens were not consistently positive when they were each amplified three separate times for the RNase H gene, they were considered appropriate for further analysis. This was because the criteria used for indicating a sample as inappropriate for further analysis was that allthree RNase H amplifications with the sample were negative.However, only HPV data of the 226 women who provided both SC and PC specimens were used for the comparisons and the analyses of agreement between the two methods, and the determination of associations between participant characteristics and the categories of HPV positivity.Out of the 46 HPV genotypes tested for, 37 and 26 types were detected with the SC and the PC specimens respectively . OverallThe six most prevalent HPV genotypes detected with the SC specimens were HPV16 (5.9%), HPV35 (4.7%), HPV40 (4.7%), HPV45 (4.3%), HPV58 (4.0%), and HPV18 (3.6%). Those detected with the PC specimens were HPV35 (2.8%), HPV58 (2.8%), HPV16 (2.4%), HPV18 (2.4%), HPV66 (2.4%), and HPV45 (2.0%). For each of the detected genotypes, a higher prevalence was obtained with the SC specimens, however, the differences were not significant; details are shown in It was noted that the vaccine-type, HPV11, was not detected at all among the women in this study . TherefoFurthermore, considering the bivalent vaccine-type HPVs (that is HPV 16 and 18), they were detected in 24 (36.4%) of the 66 self-collected specimens, which were positive for high-risk HPV types. Using the provider-collected specimens, the bivalent vaccine-type HPVs (HPV16 and 18) were detected in 12 (31.6%) of the 38 specimens that were positive for high-risk HPV types. Details are provided in χ2 = 28.943; p ≤ 0.001; Of the 244 self-collected and the 230 provider-collected specimens, 67 and 33 specimens, respectively were positive for nonavalent vaccine-type (NVT) HPVs , additional distributions are shown in k) analysis for each of the HPV infection categories (p ≤ 0.001) moderate levels of agreement for high-risk HPV infections (k = 0.402), low-risk HPV infections (k = 0.328) and overall HPV infections (k = 0.321). p-values indicating the concordances was significantly less than 100%.The Cohen's kappa  were detailed in n = 212) were negative for cervical malignant lesion and showed no dyskaryosis and intraepithelial lesions. However, 19.5% (n = 41) of them were diagnosed with other conditions, the commonest of which was bacterial vaginosis  had satisfactory smears, while 39 (15.6%) had unsatisfactory smears for evaluation. All the evaluated satisfactory smears  was lower compared to those reported for Benin, 33.2% ; BurkinaThe higher overall HPV prevalences with self-collected specimens Tables  and 5 wek = 0.24 − 0.96) have been reported between SC and PC, for both overall HPV and high-risk HPV detection [k = 0.402, k = 0.321 and 0.328). Additionally, the high level of concordance (77.9%) between the two methods, in detecting high-risk (HR) HPVs and the moderate level of concordance (67.3%) for overall HPV  obtained with SC and with PC specimens. The directionalities OR of <1 or >1) of the crude odds ratios determined with SC specimens were often as expected, as has been reported by studies and reviews of similar studies , 55–59.  or >1 ofWith these high HPV infections prevalences, it was expected that between 2.7% and 20.0% of low-grade cervical lesions would have been detected, as has been reported in some studies in West African countries with similar sample sizes , 46, 60;In respect to the Pap smear analysis , the reaThe prevaccination genital HPV infections burden among women in the Akuse subdistrict, as determined with self-collected specimens, indicated higher vaccine-type HPVs, and high-risk HPV prevalences when compared to the burden determined with provider-collected specimens. Additionally, there were multiple HPV infections which included high-risk HPV infections that are not preventable by the available vaccines, neither directly nor by cross-protection. This implies that even with a successful implementation HPV vaccination if introduced in Ghana, there is still the need to continue with the screening of women. It is therefore strongly recommended to the Ministry of Health, Ghana that self-collection (SC) and HPV testing be considered for a national cervical cancer screening programme in Ghana, particularly for the assessment of the impact of HPV vaccination.