Halyomorpha halys (Stål) is a significant agricultural and urban nuisance pest in many parts of the world. In North America, biological control of H. halys by parasitoid wasps in the families Scelionidae and Eupelmidae has shown promise. An effective technique for detection and monitoring native and exotic parasitoids is the deployment of yellow sticky cards; however, yellow cards also attract nontarget arthropods, reducing efficiency and accuracy of parasitoid screening. This study sought to identify an alternative yet effective trapping technique by comparing the number of target parasitoid wasps  and arthropod bycatch on yellow and blue sticky cards deployed in urban, orchard, and vegetable landscapes in northern Utah from late May to early October in 2019 and 2020. Yellow sticky cards captured 54–72% more target parasitoids than blue cards from June through August in all three landscape types in both years; however, a positive correlation in parasitoid capture indicated blue cards detect target parasitoids, just in fewer numbers. Both card colors detected adventive Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae) in initial findings of 2019, and in expanded locations of 2020. Furthermore, blue cards captured 31–48% less Diptera and nontarget Hymenoptera than yellow cards in both years across all three landscapes, translating to reduced card processing time and impacts to beneficial insect populations. Our results suggest that blue vs yellow sticky cards offer an alternative monitoring technique to survey for H. halys parasitoids.The invasive  Halyomorpha halys (Stål) has become a significant agricultural and urban nuisance pest in North America (Trissolcus japonicus (Ashmead) (Hymenoptera: Scelionidae), due to its efficiency in parasitizing H. halys eggs in its native range  were deployed for 14 d (±1 d) intervals beginning 29–30 and 25–28 May in 2019 and 2020 respectively, and ending on 1 October in both years, resulting in nine deployment periods in each year. Cards were deployed at 24 sites in Cache, Davis, Salt Lake, Utah, and Weber counties of northern Utah. Sites represented eight replications of three landscape types: residential urban, vegetable row crops, and fruit orchards. At each site, one yellow and one blue card were placed at approximately 2 m height and 1 m apart. Cards were attached to tree branches or metal stakes using twist ties. Manufacturer wavelength reflectance specifications for the yellow and blue cards were 575.12 nm and 466.19 nm, respectively. After collection, biodegradable plastic straws  were placed as spacers between cards to prevent adherence, and stored at –13°C until processing. The duration of card storage was variable, from a few days to several months.Anastatus spp. (Hymenoptera: Eupelmidae), Telenomus spp. (Hymenoptera: Scelionidae), and Trissolcus spp. (Hymenoptera: Scelionidae). These genera were selected because they have been observed parasitizing H. halys eggs in Utah  with 97.6x–880x magnification for the presence of target parasitoid genera, which included  in Utah  and else in Utah . Target cus spp.  since suThe number of bycatch arthropods per card was recorded by order. Counts were capped at 100 individuals per order to support sustainable processing time. The time required to count bycatch was recorded for a subgroup of 66 blue and 64 yellow sticky cards deployed between late August and early September 2020; a time period associated with moderate capture of target parasitoids and bycatch. Processing times to remove and identify target parasitoids were not included in this analysis.α was set to 0.05. Spearman’s correlation coefficient tests between numbers of target wasp captures on yellow and blue sticky cards were conducted for each year and individual landscape type. All models were conducted using various functions from packages lme4 (car (emmeans (Lenth 2020), and ggpubr , followed by Telenomus (11–28%). For both card colors, Trissolcus spp. were captured most frequently in urban landscapes, whereas Telenomus spp. were more common in vegetable sites. Anastatus spp. accounted for ≤ 2% of target wasps detected on all cards across all landscape types and years , primarily in urban and orchard landscapes for both blue  and yellow (65–67% of Trissolcus) cards. Capture of T. japonicus occurred most commonly in urban and orchard landscapes, but accounted for ≤ 9% of the total Trissolcus detected for any one card color and landscape type. Trissolcus hullensis (Harrington) was found most commonly within vegetable and orchard landscapes on blue (3–15% of Trissolcus) and yellow (7–10% of Trissolcus) cards. Trissolcus utahensis (Ashmead) occurred most commonly in vegetable landscapes on blue (18% of Trissolcus) and yellow (25% of Trissolcus) cards. There was a total of 648 unidentifiable Trissolcus spp. due to physical damage; approx. 1/4 of the captured wasps in all landscape types for blue (27–29%) and yellow (19–25%) cards (The vast majority of %) cards .Higher numbers of target parasitoids were captured on yellow compared to blue cards from late June through August in 2019  resultinr = 0.43, df = 182 P < 0.001) and 2020 . In 2019, there was a positive correlation between parasitoid captures on blue and yellow cards in urban  and orchard  landscapes, but not for vegetable  landscapes. However, in 2020, there was a correlation in parasitoid captures on blue and yellow cards within all three landscape types .Target parasitoid captures on yellow cards were positively correlated with captures on blue cards in 2019  and 2020 . The highest bycatch captures occurred in vegetable landscapes for both card colors . The vast majority of bycatch belonged to the Orders Diptera, Thysanoptera, Hymenoptera, and Hemiptera. Other bycatch was in the Orders Araneae, Coleoptera, Dermaptera, Ephemeroptera, Lepidoptera, Neuroptera, and Odonata. The mean assessment time per card required to count bycatch individuals was 3 min and 54 s for blue cards and 5 min and 40 s for yellow cards , a 1.5 times increase in processing time for yellow cards.Diptera were the most abundant bycatch taxa in urban and orchard landscapes accounting for 50% and 38% of the bycatch, respectively, on blue cards, and for 42–48% on yellow cards. Thysanoptera were the most abundant bycatch order on blue cards in vegetable landscapes (41% of the bycatch), with Diptera and Thysanoptera each accounting for 31% of bycatch on yellow cards in vegetable landscapes.Results from the linear mixed-effects model considering the mean number of Diptera and nontarget Hymenoptera revealed no interactions among card color, landscape type, or deployment in 2019; yet significant main effects revealed that more Diptera and nontarget Hymenoptera were captured by yellow than blue cards, and sticky cards deployed mid-season, specifically late June through late August, captured more Diptera and nontarget Hymenoptera  and 5. HH. halys) egg abundance  are known to commonly feed and oviposit (The majority of target wasps captured on sticky cards belonged to the genus ern Utah , 2020b, lys eggs . T. euscts occur . T. hulloviposit .T. japonicus in Utah was documented in this study. T. japonicus was detected on both card colors in Salt Lake and Weber counties in 2019 (T. japonicus.Very importantly, the first detection of  in 2019 , and expTrissolcus spp. due to physical damage caused by the sticky adhesive. These damaged specimens can result in false negatives of important parasitoid species. Fortunately, future sticky card monitoring and detection efforts will be less reliant on the morphological integrity of specimens for identification, as a new species-specific molecular identification technique for T. japonicus was recently created by Both card colors captured a large proportion of unidentifiable Telenomus was the second most commonly detected genus on both blue and yellow cards, indicating that these parasitoids are either less attracted to yellow and blue cards than Trissolcus or have smaller wild populations in the areas surveyed. Other similar sticky card surveys have documented higher numbers of Telenomus over Trissolcus species on yellow cards, indicating the observed density of genera in this study may be regionally specific (Telenomus varied across landscapes, but orchard and vegetable landscapes had proportionally higher detections, as noted in other research on Telenomus podisis Ashmead (H. halys eggs, but usually at low levels (H. halys parasitoid surveys (Telenomus to species and it is possible that captured individuals represent species incapable of stinging or successfully parasitizing H. halys (specific . The abu Ashmead . This spw levels , and has surveys . We did H. halys .Anastatus were detected on cards in this study, with no apparent card color or landscape type preference. Based on the low number of individuals captured in this genus, wild and sentinel egg mass surveys may be more effective than sticky cards at detecting species of Anastatus capable of attacking H. halys eggs (Similar to the results of lys eggs .T. japonicus detections in July and August may want to target residential urban and orchard landscapes, which capture less Diptera and nontarget Hymenoptera during this peak time period compared to vegetable landscapes. It is also important to note that this study only accounted for the first 100 specimens per order encountered on each card, which means our results underestimate bycatch, especially for Diptera and Thysanoptera which often exceeded this upper limit.Although valuable information can be gained through examination of bycatch , DipteraBombus spp., are highly attracted to the color blue (Insects in the Order Hymenoptera provide important ecosystem services . Many arlor blue , so blueRhagoletis indifferens Curran, and this may also apply to different blue colors as well. Future studies may therefore seek to compare other traps with different properties to determine the most effective approach for attracting target parasitoids and minimizing bycatch. Different types of sticky card adhesives have demonstrated differing levels of effectiveness in insect capture, but both blue and yellow sticky cards in this study contained the same type of adhesive, so this is likely not a factor in these observed differences (The current study only addresses the disparity between target parasitoid and bycatch captures on yellow and blue sticky cards. This difference may have been due to the use of a suboptimal blue card color or other physical properties. Work done by ferences .H. halys parasitoid monitoring efforts may look to adopt slightly less attractive card colors in the pursuit of decreased bycatch or target species specificity. Blue cards offer low, but consistent season-long captures of target parasitoids in urban and orchard landscapes. Blue cards documented similar seasonal parasitoid population trends as yellow cards, similar to a study that compared efficacy of different trap types for H. halys (T. japonicus in northern Utah, which is a primary target of H. halys biological control surveys in North America (H. halys, but in light of the nearly global pest status of this invasive insect, this study offers the first look into an alternative sticky card monitoring technique.Although relatively unselective trap types like yellow cards are sometimes necessary for novel or adventive insect monitoring programs where only a few potential target organisms are present , future H. halys , 2020. A America . Since b


Viral infections are emerging with diverse clinical relevance both in endemic environments and non-endemic regions of the world. Some of the viruses cause co-infections that are of public health importance. The progress of studies on human immunodeficiency virus / Human papillomavirus (HIV/HPV) co-infection is not well documented especially in Africa where cases are endemic.Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a global three-decade meta-synthesis and science mapping analysis on HIV/HPV co-infections. Assessment of progress, Author/Country productivity/trends, topic conceptual framework, and international collaborative networks were analyzed.We recovered 196 documents of 115 sources from the web of science database. The meta-synthesis revealed 1203 prolific authors containing nine solo authors, an annual growth rate of 8.09%, a significant average citation per article of 20.7%, and an average citation per year per document of 2.1. A significant high correlation between the mean/TC per article and the mean total citation (TC) per year showed 80.98% of the articles produced between 2005 and 2007 on HPV/HIV co-infection. The co-author per document index were 7.0 and the collaboration index was 6.4. The meta-analysis also revealed inadequate funding from individual or governmental organizations; among the 196 documents dataset, 114 (58.2%) were funded, and only 31 (15.8%) were funded in Africa where HIV/HPV co-infection cases are endemic.Authors’ collaboration network, countries’ collaboration, authors’ citations and implementation of research-based finding in previous studies are yet to receive the relevant outcome, especially as various countries in the African continent have received poor funding with a repeated reporting of co-infection associated with HIV/HPV. African needs to re-awaken and stir up research-based interest in HPV/HIV co-infection studies to resolve indigenous public health concerns associated with the viral endemicity. Vibrio Cholera [As of 2018, World Health Organization (WHO) describes the human immunodeficiency virus (HIV) as a ‘global epidemic’ due to the increasing distribution of the infection with types 1 , 133, an Cholera , Malaria Cholera , Drug re Cholera . Meanwhi Cholera . Current Cholera , 133. An Cholera . Accordi Cholera  living w Cholera . More ch Cholera , 130. It Cholera , 130 whi Cholera , 130, by Cholera , 97, 105 Cholera , 96, 135In recent times, reports from various investigations have shown HIV/HPV co-infection of both viruses in clinical cases. HIV/HPV co-infection is shown to be ravaging lives of many living in resources limited settlements, and conducting integrated analyses , 110, ofIn the USA, reports have revealed that there is a high incidence of cancer-related infections among HIV- infected patients with a simultaneous post-report of HPV infection amongst the general population , 115. InRecently, there has been a decrease in the HIV morbidity and mortality since the introduction of antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) , 85 for The science mapping hinged on Author/country, productivity/trends, topic conceptual framework, and international collaborative networks were analyzed. Integrated content analytics and science mapping bibliometrics analysis remains a useful research tool with an increasing potential for monitoring, handling, supporting and appraising decisions in scientific/technological progress and research development , 110. InThe “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines were used to search the Web of Science (WoS) database for relevant studies on HIV/HPV/Coinfection .clarivate.libguides.com [We collated published articles, editorial material, meeting abstract, proceedings paper, review article, on HIV/HPV co-infections from global repository data by searching the Web of Science (WoS) core collection database on 19th July 2020 at about 10.25 GMT + 2). The Boolean topic search approach applied included “(HIV* AND HPV* AND Co-infection$) OR (HIV* AND HPV* AND Coinfection$) OR (HIV-HPV* AND Coinfection$) OR (HIV-HPV* AND Co-infection$) OR (HIV/HPV* AND Coinfection$) OR (HIV/HPV* AND Co-infection$) OR (Human Immunodeficiency Syndrome* AND human papillomavirus* AND Coinfection$) OR (Human Immunodeficiency virus* AND human papillomavirus* AND Coinfection$) to recoup all available documents on the subject, “HIV/HPV co-infection” between 1990 and 2019. The Web of Science Core Collection database adopted in this study has a high reputable academic research database covering thousands of journals, books, conferences as well as millions of records from ides.com , 137. ToAll the bibliometric variables were retrieved filtered and normalized for quality control. The results were analyzed in biblioshiny package , 51, 127Our study recovered a total of 196 documents relevant to HIV/HPV co-infection from the web of science database within the survey period 1990 – 2019), with informatics and attributes as presented in Table 019, withFrom Fig. The Table In Table In Table Author co-citation network map is shown in Fig. This network confirms the position of the Authors as regards HIV/HPV coinfection research; that Munoz’s global visibility and relevance in HIV/HVP co-infection studies are attributed to researchers being specific about the content of the research than the number of publications from the research.In Fig. The top 20 institutional collaboration is presented in Fig. In Fig. The goal of this study was to provide an overview of global research publications and progress on HIV/HPV coinfection. Thereby identifying authors production/production trends, inter institutional/international research activities, conceptual topic thematic and gaps for future prospects. The findings denote a moderately increased over time number of publications, contributing countries, and the average number of authors per document. However, the number of publications that made significant contributions to the subject, the countries and the average number of citations per document was limited to the developed world.Furthermore, based on the fact that HPV infection alone is an indication of candidacy for carcinogenesis a chronic immune humiliating disease. When HPV was found in the same individuals with HIV the master of immunodeficiency in humans, then we saw the justification for the magnitude of observed co-infections in several diseases ranging from common benign warts to invasive carcinoma at various anatomical sites of infection, including the cervix, vulva, vagina, penis, anus, and oropharynx.In response to increasing global epidemic of HIV, limited studies have been gar towards its associated coinfections such as HPV. Globally, approximately 80% of the sexually active women become infected with one of the 13 high-risk HPV (hr-HPV) in their life time . Also, HHowever, the progress of studies to curbing the prevalence of HIV/HPV co-infection among women  around tFrom the forgoing in Table Here, as expected, the keyword analysis shows the search terms of interest “HIV/HPV/Co-infection” as appeared in the author keywords network Figs. , 8. The Co-citation analysis help to identify documents that contain concept, ideas, experiments, or methods that has a noble recognition, as indicated by their co-occurrence of citations . Hence, In the present day, research collaboration has increased among researchers in different field of studies , 26. ColFrom the foregoing, it is clear that the African related interest in HPV/HIV co-infection studies is relatively poor, which may have accounted for the low knowledge-scape and progress despite the introduction of vaccination and other diagnostic strides. The authors’ research collaboration network, countries collaboration, authors collaboration, citations and implementation of research-based findings in previous studies are yet to receive the aftermath, especially as various countries in the African continent have not received any related collaboration yet she is reporting co-infection associated with HIV/HPV. African needs to awake and stir up the responsibility of research-based interest in HPV/HIV co-infection studies to resolve indigenous public health concerns.Nevertheless, an increased attention and interest-based studies on the endemicity and prevalence of HPV/HIV co-infection as well as other viral pathogens be added with a view to addressing the indigenous public health concerns associated with the viral endemicity.The current study examines HIV/HPV co-infections from a bibliometric perspective. However, there was a sluggish annual growth rate, and the most relevant papers to the subject were written between 2005 and 2019, as measured by the association between the mean/TC per article and the mean total citation (TC) per year. The most prominent authors by research impact were JM Nicol AF and Williamson AL. Plos One and BMC infect. Dis. been the leading journal publishing on HIV/HPV co-infection. The conceptual factorial analysis identified two sub-fields, including cancer in women and HIV/HPV co-infection epidemiology characteristics for research engagement. In addition, the multiple-country publications and cooperation index revealed a substantial network of collaboration among researchers in developing nations. We observed that the world’s most powerful governments are investing in HIV/HPV co-infection research through disbursing funds and increasing mentorship among scholars in the region, which is missing in Africa. This study’s findings may be valuable in identifying potential partners for younger academics interested in joining the field. The study’s strength is evidenced as the first holistic content analysis and systematic science mapping of HIV/HPV co-infection research as a possible tool for widening knowledge with the ultimate goal of lowering the associated viral infection, a public health burden in Africa.However, the use of a single database may limit the identification of additional pieces of literature. Also, the keywords for data collection may have restricted the scope of the research directions. Using a threshold for co-citation analysis based on the number of total citations may hinder the use of the complete published article within the timeframe.In this bibliometric analysis, the results revealed low global research in HIV/HPV co-infection, and the publications of 2005 and 2007 were of more significant scientific relevant research outputs. The network analysis suggests that high-income countries have better interrelationship drives than low- and middle-income countries with a high prevalence of HIV/HPV co-infection and limited collaboration networks.With the increasing prevalence of HPV and high-risk HPV genotypes among HIV-infected men and women couple with asymptomatic genital distress of different degrees of severities, we recommend a reviewed narrative for future study to elaborate emerging themes and gar research focus.Countries/Regions with a high incidence of HIV/HPV co-infections requires a long-term follow up of individuals with dysplastic lesions associated with HIV infections.Based on the analysis, we recommend further scientometrics studies using a combination database involving the mapping of knowledge structure. In contract, future research should be directed towards developing and implementing vaccination and programs to reinforce the current trends of HIV/HPV coinfection. At the same time stakeholders and governments in Africa region to engage in funding and its effective ultiazation for research to the benefit of the African population.


Lung cancer has emerged as a global public health problem and is the most common cause of cancer deaths by absolute cases globally. Besides tobacco, smoke infectious diseases such as human papillomavirus (HPV) might be involved in the pathogenesis of lung cancer. However, data are inconsistent due to differences in study design and HPV detection methods.A systematic meta‐analysis was performed to examine the presence of HPV‐infection with lung cancer.ClinicalTrials.gov were searched through February 2020. A total 4298 publications were identified, and 78 publications were selected, resulting in 9385 included lung cancer patients. A meta‐analysis of 15 case‐control studies with n = 2504 patients showed a weighted overall prevalence difference of 22%  and a weighted overall 4.7‐fold  increase of HPV prevalence in lung cancer patients compared to controls. Overall, HPV prevalence amounted to 13.5% being highest in Asia (16.6%), followed by America (12.8%), and Europe (7.0%). A higher HPV prevalence was found in squamous cell carcinoma (17.9%) compared to adenocarcinoma (P < .01) with significant differences in geographic patterns. HPV genotypes 16 and 18 were the most prevalent high‐risk genotypes identified.All studies in all languages were considered for the search concepts “lung cancer” and “HPV” if data specific to HPV prevalence in lung cancer tissue were given. This included Journal articles as well as abstracts and conference reports. As detection method, only HPV PCR results from fresh frozen and paraffin‐embedded tissue were included. Five bibliographic databases and three registers of clinical trials including MEDLINE, Embase, Cochrane Library, and In conclusion, our review provides convincing evidence that HPV infection increases the risk of developing lung cancer. ACadeno carcinomaAhRaryl hydrocarbon receptorALKanaplastic lymphoma kinaseARIabsolute risk increasecIAP‐2baculoviral IAP repeat‐containing protein3E6E6 oncoprotein of human papillomavirusE7E7 oncoprotein of human papillomavirusEGFRepidermal growth factor receptorEmbasebiomedical and pharmacological bibliographic databaseEUEuropean UnionFHITfragile histidine triad proteinHER‐2receptor tyrosine‐protein kinase erbB‐2HIF‐1αhypoxia‐inducible factor 1‐alphaHPVhuman papillomavirushTERThuman telomerase reverse transcriptaseILinterleukinMCL1induced myeloid leukemia cell differentiation proteinMEDLINEU.S. National Library of MedicineNHSNational Health Servicep53cellular tumor antigen p53PCRpolymerase chain reactionPDprevalence differencePRprevalence ratiopRbretinoblastoma proteinROS1proto‐oncogene tyrosine‐protein kinase ROSSCCsquamous cell carcinomaVEGFvascular endothelial growth factorWHOWorld Health Organization1Lung cancer is estimated to be the leading cause of cancer‐related mortality worldwide, with 2.1 million new lung cancer cases and 1.8 million predicted deaths worldwide in 2018.Viral infections, such as human papillomavirus (HPV) infections have been reported to be an important risk factor of cervical cancer if genotypes with a high oncogenic risk are found. Since the first identification of human papillomavirus, more than 200 different subtypes have been identified They are classified into high‐risk HPV types  and low‐risk HPV types .2The methods of the systematic review and meta‐analysis were specified in advance and published in a protocol registered with PROSPERO. Reporting of this meta‐analysis was done according to the recommendation of Stroup et al for reporting observational studies.2.1https://harzing.com/resources/publish-or-perish), were searched. From Google Scholar, only the first 200 records  and the first 100 records  were downloaded (default sort order). In addition, WHO's International Clinical Trials Registry Platform, ClinicalTrials.gov, and the EU Clinical Trials Register were searched for completed studies. All searches were last updated on February 6, 2020. We deviated from the protocol; in that, we did not search the German Clinical Trials Register due to its search interface giving erroneous results. An initial, sensitive search strategy for the concepts “lung cancer” AND “HPV” was developed for Embase by a medical librarian in cooperation with subject matter experts and then adapted to the other databases. Controlled terms from the databases' thesauri and a broad range of synonyms were used. No limits such as for study type, publication type, publication date, or language were applied. Search strategies that allow for reproducing the searches are documented in Appendix 1. Database searches were carried out by a medical librarian. The reference lists of included studies and of relevant systematic reviews were screened for additional studies. Records from the database searches were imported into Endnote software for deduplication. Screening by title and abstract and subsequent full‐text assessment were done in Covidence. Titles and abstracts of the publications were analyzed by three independent reviewers  for relevance and matching inclusion criteria. Analysis of the publications was done according to prespecified inclusion and exclusion criteria.The digital databases Embase , MEDLINE , Cochrane Library , and Science Citation Index Expanded , as well as the search engine Google Scholar , the meta‐analysis by using the metafor package. For all comparisons, a P value <.05 was considered as statistically significant.The total number of cases, as well as the number of positive and negative HPV detections, was collected from the selected records, and HPV prevalences were calculated by means of the extracted patient data. The Chi‐squared‐test of independence was used to analyze whether prevalence rates differ between continents. Furthermore, a meta‐analysis was performed on a small subset of case‐control studies regarding HPV prevalence. Prevalence difference (PD) and prevalence ratio (PR) both accompanied with the corresponding 95% confidence intervals were estimated for each study. To estimate PR in studies with no HPV positive cases, 0.5 was added to each cell of the 2 × 2 table as usually recommended. Random‐effect models were used to determine the weighted averages of PD and PR while allowing for heterogeneity of effects. The Q‐statistic as a measurement for between‐study heterogeneity and I33.1The database searches were last updated on February 6, 2020 and yielded a total of 4525 records. Following deduplication, 3135 publications were evaluated on relevance for the research question. A total of 2754 of the titles and abstracts did not relate to the current research and were excluded. In summary, 381 publications were entered into the full text review. Full texts of three possibly relevant publications could not be obtained despite some efforts and therefore were not availableA total of 15 publications were case‐control studies, in which normal lung tissue was used as a control , China (n = 11), United States (n = 9), and Italy (n = 5). Three studies from Germany met the inclusion criteria. Six studies were done in multiple countries with the information summarized in one publication. Most of the publications were written in English (n = 73). The other publications were published in Chinese (n = 3), French (n = 1), and German (n = 1). In order to get information on as many cases as possible not only journal articles but every type of available study was included. Of the 78 included publications, 67 were journal articles. Of the remaining publications, six were abstracts, three were poster presentations, and two were meeting abstracts.3.2A total of 9385 lung cancer patients were included into this systematic review. Twenty‐eight studies provided data on the patients' age. The average age of all studies ranged from 51.6 to 70 years. Information on patients' gender was available in 52 out of the 78 studies. Those studies included 6326 patients. Of them, 62.8% were male and 37.2% were female, respectively. The percentage of male patients ranged from 0.0% to 91%. Smoking behavior was detailed in 31 of the studies. There were 3577 current or former smokers, 1958 never smokers, and in 3850 cases, no information on smoking status was available. The rate of smokers was 64.6% and ranged from 0% to 100%.3.3P < .001). Figure P < .001) as well as prevalence ratio . A forest plot summarizing the data and the effect estimates is shown in Figure df = 14) = 344.4, I2 = 95.94%, P < .001; PR: Q(df = 14) = 33.0, I2 = 57.6% (PR), P = .003].A total of 1750 lung cancer cases and 754 controls were analyzed, which were derived from 15 case‐control studies (Table 3.4P < .01 vs America and Europe), followed by The Americas  and Europe (7.0%). The highest HPV 16 prevalence was detected in The Americas (9.4%), followed by Asia (7.5%), and Europe (3.5%). Overall, the HPV 16 prevalence was calculated to be 6.1%. The highest HPV 18 prevalence was found in Asia (4.8%) followed by the Americas (2.3%) and finally Europe (0.7%). Overall, the HPV 18 prevalence was 3.1%. On all three continents, the calculated prevalence of HPV 16 was higher than for HPV 18 (P < .01). Figure Of all included patients with lung cancer n = 9385), HPV was detected to be positive in 1268 cases. The overall HPV prevalence was calculated to be 13.5%. The highest HPV prevalence was detected in Asia with 16.6%  and primary adeno carcinoma (AC) of the lung was collected. In the remaining cases, it was neither one of them or the histological subtype was not detailed. There were 2750 cases of SCC and 2887 cases of AC. In total, 29.3% of the included cases were squamous cell carcinomas and 30.8% were adenocarcinomas.The overall HPV prevalence in SCC (n = 492) was calculated to be 17.9%. The highest prevalence was calculated in Asia (28.8%), followed by The Americas (10.0%), and Europe (5.1%).The overall HPV prevalence in adenocarcinomas (n = 265) was calculated to be 9.2%. In contrast, the highest HPV prevalence in AC was calculated in the Americas (11.1%), followed by Asia (10.4%), and Europe (6.0%).P < .01), which is due to a significantly higher HPV prevalence in SCC (P < .01) in Asia, whereas no differences in prevalence were found in The Americas and Europe based on histological subtypes of lung cancer. Figure When the HPV prevalences of SCC and AC are compared, the difference is statistically highly significant  in lung cancer patients of being HPV positive, which resulted in a 4.7‐fold (95% CI: 2.7%‐8.4%) increase in the likelihood to detect HPV in patients diagnosed with lung cancer compared to healthy controls regardless of histology or stage of tumor disease.The meta‐analysis shows that the average HPV infection rate of lung cancer in the world is 13.5% based on PCR‐based assays only. PCR was permitted as the sole method to minimize differences in prevalence related to significant disparities in methodological sensitivity and specificity. Significant regional differences in HPV prevalence in lung cancer patients were found being highest in Asia with 16.6% and lowest in Europe with 7.0%. In addition, the data demonstrate a higher overall HPV prevalence in lung cancer with squamous cell histology, which is mainly due to a significantly higher HPV prevalence in squamous cell carcinoma in Asian regions since this difference was not found in squamous cell carcinoma and adenocarcinoma diagnosed in Europe and America. Most likely, the intriguing different geographic patterns of HPV prevalence in lung cancer are related to the regional differences of the HPV infection itself.Furthermore, if HPV infection was found, high‐risk genotypes with oncogenic potential were prevalently identified as well. With focus on the most common high‐risk genotypes, overall HPV genotype 16 was the most frequent genotype reported with a twofold higher prevalence compared to HPV genotype 18. With some minor modification, similar findings were reported in all different continents analyzed. These findings additionally support the hypothesis that HPV infections with high‐risk oncogenic potential significantly increase the risk of lung cancer and provide new possibilities in the future in the prevention of lung cancer by means of prophylactic vaccines for the carcinogenic HPV‐16/18 infections.The pathogenesis of HPV infection in thoracic visceral lungs is still incompletely understood. Blood based transmission through cervical lesion to the lung, high‐risk sexual behavior, and airborne transmission to the lungs have been discussed.The data of the present study provide evidence for a possible relationship between lung cancer and HPV infection, but the study fails to show a high causal interference since no longitudinal data derived from cohort studies or nested case‐control studies are given. In addition, cofounders of possible importance such as smoking status, gender, age, immunosuppressive co‐medications, oncogenic driver mutations, and estrogenic signaling pathways have not been taken into considerations, which limit the value of the results reported. Furthermore, not all HPV subtypes were assessed due to missing specification in many studies, and no transcriptional activity of the HPV genotypes found was included in the meta‐analysis. Since only PCR was included as HPV detection method but this not being the only way to detect HPV, which can potentially bias the study's results further.In conclusion, our systematic review provides evidence that HPV infection might increase the risk of developing lung cancer. Whereby relevant regional differences with respect to prevalence and histological subtypes were found with a predominance of squamous cell carcinoma. Consistently, our results support the assumption that the high‐risk genotypes HPV 16 and 18 are risk factors for lung cancer. If the understanding of the process of HPV‐related carcinogenesis in lung cancer could be further elucidated by larger prospective studies, this would facilitate the development of efficient HPV‐targeted prevention strategies.The authors have stated explicitly that there are no conflicts of interest in connection with this article.J.K., H.K., M.K., and C.S. provided substantial contributions to the conceptualization of the study. J.K., H.K., W.D., F.Z., and C.S. designed the methodology and were involved in data curation. J.K., W.D., V.F., M.K., F.K., and C.S. wrote the inital draft of the manuscript. All authors critically reviewed the manuscript, and approved the final version for publication.Not applicable.Appendix 1: Search strategies.Click here for additional data file.


Similarly, the pit depth of the GS pipe was 390 2 and 16,000 3, respectively. In addition, characterizations of new pipes were evaluated to study microstructures by using an optical microscope (OM), and a scanning electron microscope (SEM) was used to analyze corrosion morphologies. Based on the SEM analysis, cracks were observed at the sub-surface layer of the pipes. The results show that uniform corrosion attacked the external pipe surface whereas pitting corrosion damaged the subsurface of pipes. The output of this study will be utilized by water suppliers and industries to investigate corrosion phenomena at any damage stage.Water pipe surface deterioration is the result of continuous electrochemical reactions attacking the surface due to the interaction of the pipe surface with environments through the time function. The study presents corrosion characterization at the surface and sub-surface of damaged ductile iron pipe (DIP) and galvanized steel (GS) pipes which served for more than 40 and 20 years, respectively. The samples were obtained from Addis Ababa city water distribution system for the analysis of corrosion morphology patterns at different surface layers. Mountains 8.2 surface analysis software was utilized based on the ISO 25178-2 watershed segmentation method to investigate corrosion features of damaged pipe surface and to evaluate maximum pit depth, area, and volume in-situ condition. Based on the analysis maximum values of pit depth, area and volume were 380  In the designing and manufacturing process, iron-based products are favorable for making industrial products such as machine parts and pipes with the required aesthetic and functional properties. On the other hand, corrosion is a physically conditioned phenomenon of undesired results that deteriorate the integrity of iron materials which leads to damaged manufacturing products through time process. The issue of corrosion is a great problem among several stakeholders including material science engineers, water pipe distribution owners, product designers, health care, industries, hospitals, economists, researchers, etc. Moreover, buried pipes always create doubt to the owners of the distribution system due to sudden and frequent corrosion damage of the pipes.The causes of corrosion damage mechanisms of buried metallic pipes are broadly categorized as material compositions, environment, operational, and different manufacturing process phases which leads to deteriorating aesthetic and mechanical properties ,2. The fErosion corrosion which is caused by water flow and high service load. It forms a rough surface on the pipe wall due to the different degrees of corrosion damaged surface. The corrosion products of erosion–corrosion depend on the type of compound found on the surface of the pipe.3O4.Uniform corrosion that formed when the pipe thickness is reduced uniformly around the buried pipe. Such type of corrosion damage is the result of a corrosion product known as magnetite; FePitting corrosion is a localized corrosion attack forming a small hole or cavity in the metal surface. The corrosion product of pitting resulted from the interaction of iron, oxygen, and moisture or water.Stress corrosion cracking (SCC) is a form of corrosion caused by the internal water pressure and soil load. As the pressure exerts on the pipe surface, the circumferential and longitudinal stresses can cause cracks and develop corrosion with the combined action of stresses and the exposure to the corrosion conditions.Galvanic corrosion is formed between the coating material and the outer metallic surface. It can also occur in the dissimilar metallic alloying elements due to the difference in electrode potentials between the two materials.Several kinds of research have been used image processing to characterize corrosion behaviors and to interpret the damage situations such as pit depth and volume ,11 at anCorrosion damage of water pipes starts from both internal and external surfaces and continues towards the subsurface depending on the exposure time and environmental factors. The formation of external corrosion scales on the surface of buried water pipes is caused by electrochemical reactions between pipe and soil materials . Charact3O4 and Fe2O3 can be obtained through careful investigations of crystallographic structures which helps to identify corrosion mechanisms. Corrosion phenomena are complex due to a variety of parameters such as pressure which can cause unexpected pipeline failure in the chemical industry and even in the water distribution system [The interaction of pipe with environmental moisture from the environment forms hydroxyl groups (–OH) and ferrous oxides on the surfaces of pipe to form corrosion products ,15. Surfn system . To unden system . There aSoil types and compositions are inherently different from place to place due to the variability of soil mineral elements . The comBuried water pipes have been influenced by external corrosion of overlying soil and internal corrosion caused by water parameters which consequentially cause various losses including public health, cost of water treatment, and the economy at large for pipe maintenance and replacement. Among water parameters, conductivity, total dissolved solids, the deposit of trace elements, dissolved oxygen, chloride, and pH of the water are more responsible for pipeline damage. Similarly, soil corrosivity is a common problem that affects pipe service lifetime and challenges pipe manufacturers. Some soil parameters including moisture, pH, resistivity, density, soil element, and soil type are major factors that affect external pipe surface failure. During service time, the internal pipe surface wall gets rough, and turbulent and laminar flows develop into the bubbling of the water which indicates oxygen entrapment in the water forming erosion–corrosion that affects the corrosion of the pipe, severely reacting with water to form hydroxide and ferrous ions as shown in Equations (1) and (2).Corrosion can be analyzed using imaging instruments to characterize the surface and crystals of corrosion products by using scanning electron spectroscopy (SEM) to assess corrosion morphologies and X-ray diffraction spectroscopy (XRD) for studying corrosion products ,22,23. TInternal pipe corrosion can be caused by trace elements such as lead, copper, and others when deposited on the surface of pipes . On the Corroded iron pipe samples were collected from different sites of the Addis Ababa city water distribution system, Ethiopia. The specimens were dug out and cut using a hacksaw from the bulk size and GS pipe with a 100 mm diameter. Similarly, corrosion damaged of 300 mm diameter of DIP collected from the water main for corrosion characterizing at surface and subsurface in-situ condition. The study covers both surfaces inside and outside of the tubes. This is due to pipe surface deterioration was affected by the inside and outside corrosive environments. From visual inspection, more surface damage was observed at the bottom of the pipes both from internal and external surfaces. The ages of galvanized steel pipe (GS) and ductile iron pipe (DIP) were more than 20 and 40 years, respectively2, elongation of 14%, and yield strength of 207 N/mm2. The steel has British standard BS-1387 (1985). Similarly, the mechanical properties of DIP are tensile strength 480 N/mm2, elongation 18%, and yield strength 365 N/mm2. The designation of DIP pipe is ISO 2531 2009, (E) which was prepared for the analysis of microstructure.The new GS pipe has mechanical properties of tensile strength of 350 N/mmCorrosion damaged samples were prepared from two possibilities of in-situ and ex-situ conditions. The ex-situ method utilized an artificially prepared mixture of chemical forming electrolytes  whereas the in-situ technique of sample preparation utilizes natural environmental conditions. This study preferred to investigate the samples obtained naturally damaged by the soil and water environments in the loam soil. The electrical potential of soil was 0.313 dS/m, the internal pressure of 350 KPa, flow velocity of 1.5–2.5 m/s, and the length of these parameters reaction was for more than 40 years with ductile cast iron water main. The samples were then quickly taken to the laboratory to protect further atmospheric corrosion and to remove soil particles mechanically using a plastic brush and cotton cloth before analyses. After photographing, the samples were cut into sections to evaluate the internal wall of the pipes as shown in 3 for 4 s to produce a mirrored surface before analysis. Additionally, six corroded samples were cut from DIP and GS pipe with an 18 × 20 mm2 size to study corrosion morphology by using SEM-JEOL Japan, Kyoto, Japan). The SEM images were taken several times to characterize both internal and external surfaces at the micro-level with different magnifications starting from 1 mm at a decreasing size order including  μm. Below 20 μm, the image was blurred which is unable to differentiate surface details. For this study, a 100 μm scale was taken and the images were enlarged by100×–200× and 170×–220× for DIP and GS pipes, respectively. The elemental compositions of galvanized steel and ductile iron pipes were evaluated using a spark spectrometer and presented in To achieve the objectives, the authors utilized imaging instruments including an optical microscope  for analyzing internal details and scanning electron microscope (SEM) to characterize the topography of pipe materials and corrosion morphology. The laboratory analysis also focused on the microstructures of new pipes to evaluate defects from manufacturing points of view. Sample preparation of OM was carried out following standard procedures including cutting, mounting, and grinding using emery papers (grit numbers 400–2000). The samples were washed with running tap water during grinding to remove fine chips from the grounded surface before continuing to the next finer grit paper. The pipe samples were polished with a grit of 6-micrometer disc before being etched into the solution of ethanol 50 mL and 1% of HNOCorrosion-damaged pipes were excavated, cut, and covered with a paper bag to protect atmospheric corrosion and immediately taken to the laboratory for the analysis of scanning electron microscope (SEM).The image processing (IP) was utilized to characterize corroded pipes surface topographies and pitting features considering environmental and service age. It is important to characterize the degree of deterioration caused by environmental factors during service lifetime. The IP algorithm recognizes the SEM image of the corrosion damage surface and characterizes it using the watershed segmentation method to present the results in the form of graphs and tables. The morphology of pitting behaviors was evaluated based on the concept of roughness analysis of in-situ conditions from corrosion-damaged pipe surfaces. The digital image surface analysis method was developed to determine surface morphology including pit characteristics. Using Mountains 8.2 digital image surface processing software; the SEM images were analyzed following the procedures as shown in Water pipes surface corrosion inspection needs early detection to evaluate the corrosion damage status of the pipes, control water contaminants, and apply maintenance activities. Analyzing the rate of pipe surface removal as a result of electrochemical reaction is useful to determine corrosion characteristics of buried pipes in a given area with a time function. Numerous factors lead to pipe failure. Some of them are easily identified by the inspection of pipeline and its surrounding environment while others require more in-depth investigation of failure factors related to pipe material, age, manufacturing method, operating conditions, soil load, soil type, etc., as the main corrosion damage mechanisms. Internal pipe wall corrosion damage was caused by different parameters but the main pipe surface damage mechanisms were grouped into two categories; viz, deposits on the wall during the stagnant condition, and localized corrosion. The forms of corrosion formed on the water pipes during the service times are shown in 2 thin layer corrosion product and through time process which decomposes into magnetite in the presence of dissolved oxygen.Pitting was formed when the passive layer locally breaks which easily attacked the pipe surface. The process of passive layer breakage was assumed as a galvanic cell that develops an anodic site where the pipe corrodes and the undamaged area acts as cathodic protection. Pipe surface corrosion damage develops at the anode due to the loss of metallic ions and a reduction reaction is formed at the cathode which consumes electrons in the process of electrochemical reaction. As the pit depth increased, the pit acts as a pocket to hold moisture, chloride, and mineral ions able to form acidic or salty depending on the content soil parameters which accelerates corrosion rate. Corrosion damage of underground ferrous pipes begins at the outer surface and then continues to the subsurface according to the soil environmental context. Studying the chemical interaction of soil–pipe surface was crucial to identify soil behavior, applying maintenance and replacement, and predicting pipes’ operational service time. Soil moisture attacked the pipe surface by forming Fe(OH)External corrosion characteristics of buried iron pipes are influenced by the soil parameters of corrosion formation through a chemical or electrochemical reaction. This is due to underground pipe corrosion damage accelerates as the amount of moisture and oxygen increased in the soil. Soil parameters like electrical conductivity and soil type have their effect on the pipe surface damage. Ductile iron and galvanized steel pipes were mainly used for water distribution due to their mechanical advantages. However, their service life was challenged by different corrosion mechanisms such as the formation of small cracks, non-uniform coating thickness, and environmental impacts during the exposure time. Through time process, buried pipes were interacting with soil and water environments in addition to operating conditions such as water flow rate and pressure conditions. From the detailed analysis, internal and external pipe corrosion mechanisms are grouped as (1) mechanical effects such as soil load and water pressure and (2) electrochemical reaction or environmental impacts with time function. The electrochemical reaction creates different stable corrosion products such as iron oxides and iron hydroxides which are the indicators of surface deterioration. The process of pipe surface damage begins when the passive film breaks on different occasions which leads to pitting formation. As a result of this, the pits continuously propagate and penetrates the surface of the pipe at random points, and later develop uniform corrosion when colonies of pits were joined each other and the process continues till pitting termination or leakage formation. The rate of pipe surface deterioration accelerates with the presence of chlorine ion which dissolves iron particles at the anodic site. Others such as galvanic, uniform, and pitting corrosions are the failure mechanisms of water pipes. The formation pitting passes three stages; namely, pitting initiation, pitting growth, and pitting termination or leakage. At the initiation phase, the external surface including coating has direct contact with moisture and oxygen which can form films. The films then easily break due to electrochemical reaction and create initial pitting which damages the coating and then the external surface. The pits growth occurs at the second stage and damages the external pipe surface then it proceeds to the subsurface of the pipes due to the formation of depth. At this stage, stress corrosion cracking contributes the rate of pit corrosion to be faster and the size of pits grows easily. Depending on the variations in pit depth and width, a local colony of pits meets each other and the surface of the pipes deteriorates layer-by-layer as shown in The composition of alloying elements and manufacturing process were able to create defects that contribute to corrosion formation especially when there are voids and micropores in the structure. Cross-sections of metallographic structures of 4” galvanized steel water pipe were shown in The typical ductile iron pipe was used for the characterization and is shown in 3O4 and Fe2O3. The depth of the pit is increasing due to the release of metallic ions at the anode during electrochemical reaction which creates pipe surface damage. Other pit characterization topographies including maximum and minimum diameters, pitting density, the shape of pitting such as roundness were extracted from 2D pseudo color images shown in Image processing was an alternative method of analyzing pitting corrosion and surface morphology characteristics. Mountains 8.2 software was applied for analyzing corroded pipe surfaces to evaluate pit characteristics such as bit depth, area, volume, diameters, density, and roundness. The investigation showed that the analysis of 2D SEM images and the reconstructed 3D images was possible to characterize the geometric features of the pit. The software calculates using mathematical regressions based on the statistical parameters obtained from SEM images related to surface morphology and pitting conditions. The behavior of pits on the buried pipes can be deep, shallow, and wide forming rough surfaces. Maximum pit depth was evaluated by adding minimum depth (Z-min) and height (Z-max) in-situ condition after uniform corrosion attacked the thickness of the pipe during service time. The morphology showed that pitting corrosion shared a large contribution to the failure of pipe structures during long exposure of service time. Mountains surface analysis software was effective to detect the morphology of corroded surfaces at the micro-level and was able to measure pit depth, diameter, area, roundness, and volume in a small micrometer precision from the source of SEM image. The characteristics and features of corrosion-damaged surface indicated the morphology of pit depth, cracks, cavity, and peaks as shown in Corrosion is an unwanted result obtained from the reaction between the environment and materials with time function. The pipe surface deterioration caused by soil corrosivity, water environment, buried service time, and pipe materials are very important parameters that influence buried water pipes to surface damage. As the exposure time increased, the service life of pipelines decreased. Numerous factors lead to pipe failure. Some of them are easily identified by the inspection of pipeline and its surrounding environment while others require more in-depth investigation of failure mechanisms relating to pipe material, age, manufacturing method, operating conditions, soil load, soil type, etc. are the main corrosion damage mechanisms.3 (77–215 ppm), total dissolved solids (TDS) (84.10–262.8 ppm), flow rate . The topography of corroded surface filled with watershed segmentation which was generated from the SEM image as shown in In this study, the external pipe corrosion was evaluated and which was affected by the soil environmental parameters including pH, resistivity, total nitrogen, moisture, loam soil type, and bulk density whereas the internal pipe corrosion mechanisms were the low level of dissolved oxygen (80–81 ppb), conductivity (171.4–493.4 µS/cm), CaCO2. Additionally, 3 among the particles. Similarly, 2, and 1600 3, respectively, obtained from 20 years old corrosion-damaged GS pipe. Similarly, from the image processing; the pit depth of DIP was 380 2 and 200,000 3, respectively, as shown in The graph shows the roughness or irregularity of corrosion-damaged surface values ranging from 40 to 70 µm. The process of pipe surface damage was reducing pipe thickness layer-by-layer during the electrochemical process. This is due to the formation of shallow pitting corrosion at random locations and the neighboring pitting colonies joined together to form uniform corrosion. In this case, a smaller pit depth was created on the remaining surface of the pipe. For example, the pit depth up to 400 μm can be categorized as uniform corrosion. On the other hand, localized pitting corrosion created a cavity and perforation of pipe surface while the pits grow with the function of time and environmental factors 3O4 while brown color was identified as Fe2O3. The white color ZnO was observed at some random points on the surface of the pipes and the geometry of corrosion had different sizes, shapes, and depths of localized corrosion. A corrosion pit was caused by scratch, localized surface defect, environmental corrosion, and variations of alloy compositions. Corrosion products have different colors such as white, red, and brown The surface irregularities observed on both internal and external surfaces were a result of soil and water effect during long-run service years. After the protecting of zinc coating has oxidized, the steel surface begins to form corrosion scales around the pipe and localized corrosion damage continued to the subsurface of the pipes even further attacked the whole pipe thickness. The internal pipe corrosion was a result of hydraulic operating conditions that influence the formation of erosion–corrosion and cracks due to water pressure and the effect of stagnant water during a steady time. In this study, as compared with corrosion resistance between GS and DIP, both pipes have different corrosion rates. The DIP pipe had more corrosion resistance capacity than GS due to variations of parameters including the thickness of the pipe, coating type, pipe compositions, and buried depth. For example, the thickness of DIP and GS pipes were 8 mm and 5 mm, respectively. Similarly, the buried depth of the DIP water main was 120–150 cm whereas the GS pipe is buried at 80 cm depth for 100 mm diameter. Due to mechanical properties and coating type of bituminous coating, DIP pipe is more corrosion-resistant than GS pipe. From a variety of corrosion characterizing methods, the results show that pitting corrosion is the main pipe failure problem of water pipes. The external pipe surface of the DIP pipe is affected by uniform corrosion. Similarly, the internal pipe wall was damaged by a corrosion pit and crack. The subsurface was affected by the crack due to water pressure and narrow pits. In general, pipe surface damage was a complex problem due to the combined effect of electrochemical reactions and stresses applied to the pipe. This study explored characterizations of corrosion morphologies at the surface and subsurface of corrosion-damaged iron-based water pipes. The proposed method of corrosion characterized using Mountains 8.2 digital image surface analysis software was used to analyze corrosion damaged surface at any stage up to particle level. The acceptability of corrosion defects was evaluated using image processing based on the ISO 25178-2 standard, microstructure analysis, and corrosion morphology characteristics. The rate of corrosion was more at the subsurface of the pipes than the outer surface as a result of pit depth growth. The SEM analysis confirmed that micro-cracks were observed at the subsurface due to water pressure and pitting depth. On the other hand, microstructural evaluation using OM showed the grain size and boundaries of the structure were observed as uniform distribution of alloying elements. From the various characterization techniques, the rate of corrosion deterioration process was categorized as: (1) pipe coating corrosion damage; (2) external pipe surface weakening; and (3) subsurface corrosion degradation and failure of pipe structures. This study provided a basic understanding of water pipe corrosion damage processed at the surface and subsurface of the pipes to understand the causes of water quality deterioration and structural failure. The outcome of this study will be important for the water distribution system, pipe manufacturers, and industries to control corrosion at an early stage.


P < 0.01). Our finding suggested a direct significant association between Pb accumulation and CIN existence. The consequences need to be further validated by including more relevant risk factors and controlling the confounders for better understating of Pb impact from outdoor air pollution on cervical cancer progression.Human papillomavirus genotypes (HPVs) have been confirmed to be the major cause of cervical intraepithelial neoplasia (CIN) that remains to be one of the most common women cancers around the world. It seems other risk factors have synergistic effects on cervical cancer occurrence including smoking, dietary pattern, sexual behavior, ethnicity, epigenetics, and environmental hazardous materials. Our study characterized the potential cancerous role of lead (Pb) as a common toxic environmental pollutant agent on CIN outcomes. Lead concentration was quantified using an atomic absorption spectrometer in liquid-based cytology specimens of 40 CIN-HPV positive subjects, 50 HPV infected non-cancerous cases, and 43 non-HPV infected/non-cancerous women. Pb concentration was 5.5 (4.7–6.4) μg/dL, 4.7 (4.2–8.7) μg/dL, and 4.7 (4.5–5.4) μg/dL in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous group, respectively. The results showed higher Pb concentration is associated with higher risk for cervical malignancy in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect (aOR = 4.55, 95% CI: 1.55–15.07,  Tehran, a metropolitan city with a population of more than 10 million people, is one the most polluted areas throughout the world. Air pollution is a life-threating factor caused by urbanization and industrialization especially due to fuel vehicles. Therefore, it seems traffic congestion is a common source of Pb emission to the environment  remains to be a severe public health concern in undeveloped countries lacking preventive medical resources and organized health screening programs. The incidence of cervical cancer varies in undeveloped and developed communities from 11.3 to 18.8 per 100,000 women in 2020, respectively. Several potential risk factors including HPV infection, life style, and self-awareness have been associated to cervical and genital malignancies . The AA spectrometer was equipped with a GTA120 (graphite tube atomizer) and an auto sampler. Pyrolytic ally–coated furnace tubes were employed and trace metal–free polycarbonate tubes were used for sample preparation. GFAAS conditions: 283.3-nm wavelength, 7A slit, D2 background correction, grooved furnace tube. Dry: ambient to 125 °C in 15-s ramp, 5-s hold. Ash: 125 °C to 600 °C in 45-s ramp, 20-s hold. Atomize: 600 °C to 2400 °C in fast ramp or step, 5-s hold.Pb was measured using an atomic absorption spectrometer (Agilent technologies/200 SeriesThe Milli-Q water was purified by de-ionization with a Milli-Q system (Millipore) for washing all laboratory wares, solutions, and standards preparation. In addition, all reagents were obtained from Merck Co. Working standards were prepared daily by serial dilution of a master standard with 0.1% v/v nitric acid. Dilution ranges of Pb standards were made and vortexed by 0, 1, 5, 10, 25, 50, and 100 μg/dL for working standard solutions. Calibration was also performed directly using aqueous standards.One hundred microliters of samples was diluted with 400 μL of “Matrix modifier” . The Pb concentration of samples was calculated from integrated absorbance measurements and calibration graph. Analysis was performed with 20-μL loads under the following GFAAS conditions.n = 20) and 2.7 at 25 μg/dL (n = 20). The recovery of 25 μg/dL was 97.2%. The accuracy was checked by analyzing standard reference materials: Seronorm™ (Trace Elements Serum), an accuracy control for analysis of trace elements and heavy metals  signal that was 0.2 μg/dL, corresponding to a limit of quantification (10× SD) of 0.6 μg/dL. Precision was 6.7% at 10 μg/dL  and corresponding 95% confidence intervals (CIs).Pb concentration was investigated as numerical variable and presented in the CIN-HPV positive group, HPV infected non-cancerous cases, and non-HPV infected/non-cancerous subjects. As the Pb concentration had a skewed distribution in the study population, it was summarized using median value and corresponding interquartile range in each group and compared using non-parametric methods. Specifically, we used the Mann-Whitney U test. Comparison of Pb concentration was also performed between multiple HPV genotypes using the Kruskal-Wallis test. The statistical analysis was conducted using R software (version 3.6.1), and a two-tailed P value ≤ 0.05 was regarded to be statistically significant.In addition, we studied the Pb concentration in different HPV groups based on their genotypes. Findings were presented as boxplots and summarized using median values and interquartile ranges. The difference of Pb concentrations was compared between HPV infected and non-HPV infected women by the Mann-Whitney P < 0.01). As a result, when controls were divided into HPV infected and non-HPV infected, Pb level in the case group was only statistically higher than non-HPV infected women (P < 0.01). The median Pb concentration was also different within CIN grades-HPV positive group (P = 0.019). The outcomes are presented in Table Pb concentration was measured on 133 women and median concentration of Pb was higher in the cancer group compared with the total control group (Pdifference = 0.04). In the non-HPV infected/non-cancerous group, Pb concentration was higher in the younger age group and was negative linearly correlated with age , while such a pattern was not observed in HPV infected non-cancerous cases.The difference of Pb concentrations was also examined in two age groups and its potential linear correlation with age as a numerical variable, in each study group. Outcomes are shown in Table P < 0.01), as well as in comparison with the control group without HPV infection . No statistical significance was observed between Pb and CIN-HPV positive group in comparison with the HPV infected control group. The association between ternary Pb level and CIN  was conducted in comparison with different control groups. After controlling for age effect in the regression model, higher level of Pb concentration was associated with a higher risk for CIN in comparison with the total control group . The detailed outcomes are mentioned in Table P < 0.01).The association between binary Pb level and CIN was compared between the CIN-HPV positive group, HPV infected-non cancerous subjects, and the non-HPV infected/non-cancerous control group. The results are shown in Table Pb concentrations of different HPV genotype groups are demonstrated in Fig. Women could possibly be more exposed to Pb, as a toxic element for multiple organs and cancers at even a low dose after a long-term exposure, through ambient environment, cooking, and cosmetics. In line with our results, a previous study also reported a higher Pb level in CIN endo-cervical tissues, compared to histological normal tissues. Notably, their study had 3 CIN cases, while our study focused on a bigger sample size, ensuring a better statistical power (Rzymski et al. Specifically, it seems women smokers have a higher Pb concentration in the endo-cervical tissues than non-women smokers, although we could not access smoking habit data of the current study. However, it seems the prevalence rate of tobacco smoking is less than 5% among Iranian women (Sohrabi et al. Microbial pathogens might also play a synergistic role for carcinogenic heavy metals and trace element existence in cervical cancer progression (Fenga et al. Our study adds up to the direct evidence that higher Pb level accumulated in tissue of cervical neoplasia. It seems it is associated with higher risk of cancerous changes. There are also significant drawbacks in our study. Firstly, our study could not exclude the effects of factors that may have a significant impact on Pb exposure such as smoking habits, education level, living conditions, and working environment. Albeit, smoking habit is not common in Iranian women. We considered the various risk factors and variables in the study questionnaire, but they have missed meanwhile the sample collection. Therefore, insufficient factors were excluded for biostatistical analysis. Secondly, we could not elucidate the possible causal relationship between Pb exposure and cervical cancer in the current setting. Pb could trigger cancerous changes in cervical tissues related to HPV genotypes.Here, the study showed an association between increase of cervical Pb concentration and progression of cervical intraepithelial neoplasia in comparison with non-HPV infected/non-cancerous subjects, after controlling for age effect. As a result, the higher level of cervical tissue Pb concentration was associated with a higher risk for CIN subjects in comparison with total control studied and non-HPV infected control. Therefore, further dedicated attempts are needed to validate the outcomes by including more relevant risk factors, appraising the source of Pb exposures and finding any correlations particularly from outdoor air pollution and its consequences on cervical cancer progression.


Introduction: Human papillomavirus (HPV) is associated with six types of cancer in men and women. A vaccine against HPV, preferably administered before initial sexual intercourse, has been proven to be highly effective in preventing these cancers. An effective healthcare provider recommendation has significant influence on HPV vaccine uptake; therefore, it is critical that medical students receive comprehensive training in this area. Aim: The aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus’s (HPV) ways of transmission, risk of cancer development, and vaccination against HPV. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others. Materials and Methods: The study was conducted among 1061 (678 women and 383 men) medical students who filled in our questionnaire. The medical students were divided into two subgroups: (1) pre-clinical medical students  and (2) clinical medical students . Results: A total259 (24.41%) of the 1061 medical students were vaccinated against HPV. We found a significant improvement in the general level of knowledge in the later years of education (4–6) compared to the early years of education (1–3). However, it was demonstrated that, despite medical education advancements, there are still significant gaps of knowledge about the relationship between HPV infection and cancers other than cervical cancer, as well as in relation to the routes by which HPV is transmitted. Medical students’ intentions to recommend HPV vaccine to others were related to their own HPV-related knowledge and their own vaccination status. Conclusion: Medical students have gaps of knowledge regarding particular issues and aspects of HPV. It is necessary to further educate medical students in the field of prevention and in the treatment of lesions caused by HPV infection. Medical students’ intention to recommend the HPV vaccine can be improved by including them and members of their families in the HPV vaccination program. HPV has over 200 subtypes, the most dangerous of which are the oncogenic subtypes, whose current number is about 15 . GynecolInitially, HPV vaccination programs were female-only programs. However, it has been demonstrated that HPV infection significantly increases the risk of development of other types of cancers, e.g., anal cancer, oropharyngeal cancer, laryngeal cancer, penile cancer, and vulvar cancer. It is estimated that 90% of cases of anal cancer are caused by HPV infection . In the In particular regions of the world, HPV vaccination programs are recommended for both women and men. Particularly high vaccination efficacy rates of about 70% in men and 80% in women were obtained in Australia ,11. It iIncreasing HPV vaccination rates is in the interests of society. Achieving this goal requires a multi-pronged measures, including conducting campaigns and educational programs for society and developing a proper training system for healthcare professionals, including students of medical universities . TherefoThe aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus’s (HPV) ways of transmission, the risk of cancer development, and vaccination. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others.The study was conducted among 1061 (678 women and 383 men) medical students at Karol Marcinkowski Poznan University of Medical Sciences between November 2019 and December 2019 . After aA self-designed questionnaire (32 questions) was created after analysis of the available literature. The first part of questionnaire contained nine questions about basic characteristics and personal sexual history. The second part of the questionnaire included fifteen questions concerning knowledge of HPV and HPV vaccination. The internal consistency of the questionnaire assessing knowledge on HPV was performed by Cronbach’s alfa coefficient. For our HPV knowledge questionnaire, Cronbach α level was 0.70. The last part of the questionnaire contained eight questions about HPV awareness and attitudes towards HPV vaccination.A pilot study was carried out among 20 medical students of the Poznań University of Medical Sciences in order to test and evaluate the questionnaire in terms of clarity and completeness of the questions asked. After taking into account the suggestions of the students participating in the pilot study and introducing the suggested changes, the proper study was launched. The questionnaires were distributed to the students in classrooms at the beginning of lectures. The participants were informed as to the purpose of the study. Each participant provided written consent to participate in the study. Time to fill in the questionnaire was unlimited, but it usually took no more than 10 min.Each participant in the study scored 1 point for giving a correct answer, and no points were awarded or deducted for an incorrect answer or the answer “I do not know”. Students were compared in terms of the point numbers and the percentage of correct answers they obtained by completing the questionnaire. The levels of knowledge were described by median, mean, standard deviation, and percentage of correct answers. Student’s t-tests were used to compare the two groups. A comparison of the percentages of responses between the analyzed groups was made using a test of proportions.A logistic regression model, both univariate and multivariate, was used to analyze the relationships between specific factors  and the recommendation of HPV vaccination among medical students. The results of the analysis are presented as an odds ratio (OR) and a 95% confidence interval (95% CI). For the multivariate logistic regression model, a stepwise backward selection was used.http://statistica.io, accessed on 20 April 2020. All tests were analyzed at the significance level of p = 0.05.The calculations were made with the use of TIBCO Software Inc. (2017) Statistica , version 13. The estimated sample size of 310 students was required for a 5% margin of error and a 95% confidence interval (CI). A total of 1155 students participated in our survey. Finally, 1061 of them who fully completed the questionnaire were included in the study. Incomplete or incorrectly filled in questionnaires were eliminated from the analysis. The number of questionnaires is therefore sufficient to assess the level of knowledge in particular groups of students and to find statistically significant differences between them.p < 0.001). Moreover, heterosexual students had a lower level of knowledge than homosexual/bisexual students (p < 0.001). Furthermore, students with a permanent sexual partner showed a higher level of knowledge than students without a sexual partner (p < 0.001). A higher number of sexual partners in the past was also associated with a higher level of knowledge (p < 0.001).The mean score  among all the respondents was 11.74 ± 2.51 points out of a maximum of 15 points . First op < 0.001) (p < 0.001), as well as in the field of genital warts (question-5) (p < 0.001) and in the field of differential diagnosis with the Herpes Virus (question-6) (p < 0.001). Medical students (both early and late years) showed significantly less awareness of the HPV-related risks of cancer development in locations other than the cervix, such as the anus, the penis, and the vulva. Moreover, our study demonstrated that medical students in later years of study had a significantly higher level of knowledge about the possible routes of HPV transmission than those in their early years of study (questions 12 and 13) (p < 0.001). In the question about vertical routes of transmission as a source of HPV infection (question 14), students in years 1–3 were more likely to give the correct answer that vertical transmission is associated with a potential risk of HPV infection than students in years 4–6 (p < 0.001); however, both groups of medical students had a low level of knowledge in this matter. Finally, we found that in relation to the question about the recommended age for HPV vaccination (question 15), students in later years of study gave the correct answer more often (p < 0.001).Our study also demonstrated an improvement in HPV knowledge among medical students who were more advanced in their education. Students of higher years of study (4–6) had a higher level of knowledge about HPV and HPV vaccination than students in their early years of study (1–3) (< 0.001) . First op < 0.001)  . Overall< 0.001) . Among mThe study performed by our research team is an analysis that assesses the state of knowledge about HPV and preferences in terms of HPV vaccination among Polish medical students with respect to sex, degree of education, sexual data, and experience with HPV vaccination (respondent was vaccinated or a member of the respondent’s immediate family was vaccinated).Our analysis has shown a significant improvement in the level of knowledge about HPV among students, along with progress in the educational process. Moreover, it was demonstrated that students who have already experienced sexual intercourse and students who have had more sexual partners in the past scored better in the survey. The above results are consistent with the data obtained by the WHO, which assume, above all, a positive effect in terms of public health and an increase in awareness among the public  based on prevention measures, including information and education, implemented on a global scale .One of the few sources we can rely on is a study from a culturally distant part of the world, i.e., China, in which 1878 medical students were examined. This was a multi-center study, which included six selected universities from south-western China . The stuIn the general population, even in countries where educational programs on the prevention of HPV infection have been implemented, the level of knowledge is insufficient and, surprisingly, has deteriorated over the last decade . The lowp < 0.001). However, about 20% of medical students in their final years of study are not aware of the relationship between HPV infection and the increased risk of developing cancer in other locations, i.e., the penis and anus. These results are reflected in studies conducted by other research teams, which indicate a lack of knowledge among medical students in this field [Another issue raised by our research team was the assessment of the state of knowledge on the relationship between HPV infection and increased risk of developing particular types of cancer. We observed a significant general improvement in the state of knowledge in this field, along with progress of the educational process but, in the case of the analysis of individual cancers, there were some significant differences that require separate commentary. First of all, it should be emphasized that almost all students in both their early and late years of education are highly aware that HPV infection increases the risk of cervical cancer. Our analysis also shows that students in their early years of study are significantly less aware of the increased risk of developing cancers in other locations. Importantly, we observed that the system of training in the medical program contributes to a significant improvement in the knowledge of medical students, particularly with regard to head and neck cancer . Moreover, the HPV vaccination coverage of Polish teenagers is even lower, and is estimated to be 7.5–10% . In PolaPolish medical guidelines also provide recommendations for conducting HPV vaccination in young boys aged 9–15 . This isAn important issue that has been raised by our research team concerns the factors that predict the attitude of medical students when it comes to recommending HPV vaccination. The vast majority of respondents who participated in our study would recommend HPV vaccination, and most of them believe that HPV vaccination should be mandatory. In our multifactorial analysis, we have shown that medical students were more likely to recommend HPV vaccination to both women and men if the following criteria were met: they had higher level of knowledge about HPV, they were vaccinated against HPV, or a member of the respondent’s immediate family was vaccinated against HPV. These results are consistent with the results of other studies, where a better general level of knowledge about HPV and positive HPV vaccination status have been shown to be positive predictive factors ,27. ThesFinally, our study found that medical students also have gaps in their knowledge about HPV protection methods and HPV transmission routes. More than 90% of all respondents are aware of the fact that condoms contribute to reducing the risk of HPV infection. However, one in five medical students in their early years of education are not aware that HPV infection is possible during anal or oral sex. Moreover, only half of the students are aware that the HPV virus may also be transmitted vertically. This shows that medical students do not have full knowledge of this important matter. These results are confirmed in other research papers, which show, for example, that a significant proportion of respondents are wrongly convinced that the use of condoms provides fully effective protection against HPV infection .It has to be emphasized that our study has several limitations. First of all, the data were collected in only one region of Poland and the medical students attended only one medical school. The HPV-related curriculum provided by the university where the study was performed mostly concerned the virus’s molecular and epidemiological aspects. Undoubtedly, the provided curriculum also does not include training in more practical aspects such as methods of recommendation HPV vaccination to others. Finally, the study was performed using a researcher-designed questionnaire; however, there is no validated questionnaire in this area.Increasing HPV vaccination rates in society has proven to be a cost-effective intervention that prevents HPV infection and various types of cancer. Educational programs and a proper training system for healthcare professionals, including students at medical universities, are crucial for achieving this goal. We demonstrated that, despite medical education advancement, there are still significant knowledge gaps about HPV. Our survey showed data that can be useful in the design of future HPV programs and services, as they highlight gaps in the education  of future medical professionals. Finally, we also demonstrated that the attitudes of medical students when it comes to recommending HPV vaccination to others can be improved by encouraging them, as well as members of their families, to take up HPV vaccination.


Some studies suggest that Human Papilloma Virus (HPV) infection is important factor in carcinogenesis of breast tumors. This study’ objective was to analyze HPV prevalence in breast cancers of patients from south-central Poland.The study was performed based on archival paraffin embebbed and formalin fixed blocks in the group of 383 patients with breast cancer. HPV prevalence and its genotype were assessed, respectively by: nested PCR (with two groups of primers: PGMY09/PGMY11 and GP5+/GP6+), quantitative PCR (qPCR). Tumors were classified as HPV positive in case of at least one positive result in nested PCR and positive results in genotyping procedure. For all HPV positive tissues P16 immunostaining was applied in order to confirm active viral infection.In the group of 383 breast cancers, HPV positivity was found in 17 samples (4.4%) in nested PCR. All these samples were subjected to HPV genotyping. This analysis revealed presence of HPV type 16 into two tumors (0.5%). In these two cancers, P16 overexpression was reported.In breast tumors of patients from south-central Poland in Poland, HPV positivity is demonstrated in very low percentage of cases. Helicobacter pylori, high risk Human Papillomavirus (HR-HPV) and Hepatitis B and C viruses. In 2018, HR-HPV infection was responsible for 690 000 new diagnosed cancers [According to the analysis based on the GLOBOCAN database from 2018, 2.2 million infection-attributable cancers  were diagnosed [ cancers  to 5.9 [HPV presence in breast cancers can occur from direct skin to skin contact during sexual intercourse or in case of woman with previous history of HPV positivity in the cervix trough nipple or micro-lesions or body fluids  . It is hData concerning prevalence of HPV in breast cancers are, however, inconsistent. The percentage of HPV positivity in these type of tumors varied between individual studies from 0.0 , 11–21 tInitially, formalin–fixed paraffin emedded tissue blocks (FFPE) were gathered from 448 patients with infiltrating invasive ductal breast cancer in clinical stage T1–2, N1–2, M0, treated in Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Krakow Branch, Poland between 1992 – 2006 .The study was approved by the Ethical Committee at the Regional Medical Chamber in Cracow (Poland) . Informed consent was obtained from all individual participants included in the study. All samples were anonymized.+ (32.6%) and luminal B HER2− (24.1%) immunophenotypes.For all cancers, their immnunophenotypes was assessed based on estrogen, progesterone, and HER2 immunoexpression (or hybridization in situ in case of inconclusive results of HER2 immunostaining), according to St. Gallen International Expert Consensus on The Primary Therapy of Early Breast Cancer 2013 . Before β-actin gene using TaqMan® Gene Expression Assay , with mix of specific primers and MGB probe as described earlier [DNA was extracted using 4 μm thick FFPE Sects. (3–7 depending on sample size) using ReliaPrep™FFPE gDNA Miniprep System  based on manufacturer`s suggestions with our own modification. All details concerning this procedure were described earlier . In brie earlier .The nested PCR involves two pairs of primers—outer , used in two successive PCR runs, what allows to detect L1 gene fragment of multiple HPV types during one experiment. The product of the first reaction serves as a template in the second reaction. Sequences of primers, composition of reactions mix and conditions of PCR reactions were described earlier . To asseL1 gene amplification. The reaction was carried out according to manufacturer`s protocol and all its details were presented earlier [For all HPV positive samples in nested PCR (at least one positive result), virus genotyping with AmoyDx® Human papillomavirus (HPV) Genotyping Detection Kit  was performed. This procedure allows for genotyping of 19 high risk HPV  and 2 low risk (6 and 11) on the basis of virus  earlier . As a ne earlier .Expression of P16 was analyzed in the group of 383 tumors using CINtec® Histology Kit  according to the manufacturer’s procedure, described by us earlier . In brieFor all 383 DNA samples 100.0%) extracted from FFPE, amplification of β-action was noticed. HPV positivity in nested PCR was found in 17 samples (4.4%), at least in one reaction in 15 samples and in two reactions in two cases , we have found HPV prevalence at the level of 0.5% (2 cases). These two tumors were also characterized by P16 overexpression , special attention must be paid on type of material using as a source of HPV DNA. In the present study, we have used nested PCR with GP5+/6+, MY09/11 and PGMY09/11 set. In relation to this set, we would also like to pay attention on results of Erhart et al. , who havP16 gene , found in nearly 50% of malignancies, can inhibit synthesis of this protein [In the present study, we have found P16 positivity in two HPV16 positive BC, whereas all HPV negative BC in PCR analysis were also negative for P16 expression. Expression of P16 is a known surrogate marker of HPV infection . However protein . Therefo protein  or recta protein .Presented by us results demonstrated very low percentage (0.5%) in breast tumors of patients from south-central Poland, what suggest that in this region HPV infection has no influence on development of breast tumors. Our study has some limitation related with the fact that it is case study without control group. However, case–control study is not suitable to study rare exposures, as in the case of the presented analysisy, in which the percentage of BC positivity is at the level of 0.5. It should be also noticed that in the light of contrary results concerning HPV prevalence in BC, future studies are needed to fully explain the association between this infection and development of breast cancer.