P = .033). Active surveillance might reduce the severity of those progressed to cancer. Because a majority of the patients with recurrent CIN2+ had persistent type‐specific HPV infections, effective therapeutic vaccines are an unmet medical need.Human papillomavirus (HPV) is the well‐established etiologic factor for cervical neoplasia. Cervical conization constitutes an effective treatment for high‐grade cervical intraepithelial neoplasia (HG‐CIN). We conducted an observational study for long‐term outcomes and HPV genotype changes after conization for HG‐CIN. Between 2008 and 2014, patients with newly diagnosed HG‐CIN before conization (surveillance new [SN] group) and those who had undergone conization without hysterectomy (surveillance previous [SP] group) were enrolled. HPV testing and Pap smear were performed periodically for the SN and SP (collectively S) groups. All other patients receiving conization for HG‐CIN during the study period were identified from our hospital database. Those eligible but not enrolled into our study were assigned to the non‐surveillance (non‐S) group. For the S group (n = 493), the median follow‐up period was 74.3 months. Eighty‐four cases had recurrent CIN Grade 2 or worse (CIN2+) (5‐year cumulative rate: 14.8%), of which six had invasive cancer. Among the 84 patients, 65 (77.4%) exhibited type‐specific persistence in the paired HPV results, whereas only 7 (8.3%) harbored new HPV types that belonged to the 9‐valent vaccine types. Among the 7397 non‐S patients, 789 demonstrated recurrent CIN2+, of which 57 had invasive cancer. The stages distribution of those progressed to invasive cancer in the non‐S group were more advanced than the S group , a cervical carcinoma precursor, frequently is caused by high‐risk human papillomavirus (hr‐HPV) infection. HG‐CIN can be treated by cervical conization, though the procedure does not eradicate hr‐HPV, potentially enabling CIN recurrence. Here, in Taiwanese patients, investigation of HPV genotype changes in relation to HG‐CIN status after conization shows that 77.4 percent of patients with recurrent CIN 2 grade or worse (CIN2+) after conization had persistent type‐specific HPV infections. Vaccination against the remaining high‐risk HPVs prevented recurrent CIN2+ in only 8.3 percent of patients, revealing an unmet need for effective therapeutic vaccines. ASCCPAmerican Society for Colposcopy and Cervical PathologyCIconfidence intervalCIN2+CIN Grade 2 or worseFFPEformalin‐fixed paraffin‐embeddedFIGOFederation of Gynecology and ObstetricsHG‐CINhigh‐grade cervical intraepithelial neoplasiaHPVhuman papillomavirushr‐HPVhigh‐risk HPVHRshazard ratiosLEEPloop electrical excision procedurelr‐HPVlow‐risk HPVnon‐Snon‐surveillanceSNsurveillance newSPsurveillance previous1Cervical carcinoma is a multistep slow‐developing disease and is often preceded by high‐grade cervical intraepithelial neoplasia (HG‐CIN); human papillomavirus (HPV) is the well‐established causative agent of HG‐CIN.Data on HPV distribution in HG‐CIN and cervical carcinoma patients are essential for understanding the natural history of HPV‐associated cervical lesions. HPV16 has consistently been the predominant HPV type worldwide, both in HG‐CIN and cervical carcinoma patients. However, its absolute prevalence and the distribution of other genotypes vary in different countries and ethnic groups.Cervical conization constitutes an effective therapeutic treatment for HG‐CIN and early invasive cancer; however, this treatment cannot eradicate hr‐HPV completely. Wide‐ranging recurrence rates of CIN after conization of 0.35% to 69% were reported.In our study, we evaluated a post‐conization surveillance strategy involving follow‐up of Pap and HPV status of HG‐CIN patients treated with conization to delineate HPV subtype changes, and we compared the cumulative recurrence/progression rate in these patients with that in usual‐care patients.22.1We conducted a prospective observational study of patients who were newly diagnosed with HG‐CIN before conization (surveillance new [SN] group) and those who had received conization without hysterectomy (surveillance previous [SP] group) at Chang Gung Memorial Hospital and were willing to participate from the point of signing an informed consent form. Conization with the loop electrical excision procedure (LEEP) was most frequently performed, and cold knife or laser excision was chosen occasionally depending on the individual clinical scenario. For the SN group, HPV testing was performed before conization. For all surveillance  patients, cervical and vaginal cytology and HPV testing were performed every 6 months (except that the first post‐conization visit could be conducted between 3 and 6 months) and every year for those who had no events  in the 5 years after conization. Those with HPV‐positive results or abnormal Pap smears underwent colposcopy and directed biopsy, as indicated. For SP group patients, the follow‐up method in non‐S group was cytology alone 6 to 12 months. Their cytology/pathology results  as well as HPV testing results (some of them had HPV tests) before enrollment were retrieved from our hospital database. HG‐CIN events in the SP group after initial conization and before enrollment were recorded as a recurrent HG‐CIN event, and long‐term outcomes were analyzed. All the S group patients gave their written consent, and the study was approved by the institutional review board .Total HPV clearance was defined as HPV‐negative results throughout post‐conization follow‐up. Subsequent total clearance was defined as HPV‐negative results in at least two visits by the end of the study, despite HPV‐positive results in earlier post‐conization visit(s). Patients with negative results during follow‐up that turned positive were not considered to have HPV clearance. Type‐specific clearance was defined as negative results for a specific HPV type at two visits without reappearance at subsequent follow‐ups. Time to HPV clearance was defined as the time from initial conization of patients with HPV‐positive HG‐CIN to the first of the two visits with HPV‐negative results. HPV acquisition was defined as detection of HPV after at least two preceding visits with HPV‐negative results.2.2DNA was extracted from formalin‐fixed paraffin‐embedded (FFPE) tissue or swab cervical specimens, as previously described.2.3In our study, recurrence/progression was defined as diagnosis of HG‐CIN or cervical cancer (CIN Grade 2 or worse [CIN2+]) at least 3 months after the initial diagnosis. Those diagnosed with HG‐CIN within 3 months were considered to have persistent disease. Those diagnosed with invasive cancer within 3 months were considered to have invasive cervical cancer with the initial conization under‐diagnosis. If multiple events occurred in the same patient, the time to recurrence/progression was defined as the time of the first HG‐CIN event. The time‐dependent HPV infection status of the study patients was evaluated from first conization to the date of the last follow‐up visit, progression to cancer, or hysterectomy. Patients with multiple infections were categorized by the order of cervical cancer prevalence .The SP group patients had their earliest diagnosis of initial HG‐CIN in June 1995, and the last S group patient was enrolled in December 2014; therefore, all patients diagnosed with HG‐CIN between June 1995 and December 2014 were identified from the hospital database . All tests were two‐sided, and a P value of <.05 was considered statistically significant.Between‐group comparisons of cumulative recurrence were based on the Kaplan‐Meier method and log‐rank tests. Pearson's chi‐square test or Fisher's exact test was used to evaluate proportion differences between designated groups. Their hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Continuous covariates were compared between groups using both parametric and nonparametric approaches, mainly, the Student 3P < .001). The median follow‐up period of the SN group  was significantly shorter than that of the SP group  (P < .001). CIN was more severe in the non‐S group than in the S group (P = .019), whereas the difference in the CIN grade or margin status between the SN and SP groups was not significant.A total of 493 patients  were enrolled between June 2008 and December 2014 for this longitudinal surveillance study. A total of 8852 patients who were diagnosed with HG‐CIN between June 1995 and December 2014 were not included in the S group. After excluding patients with cervical cancer diagnosis (n = 696) at initial conization and those who underwent hysterectomy within 3 months after the initial HG‐CIN diagnosis (n = 759), the remaining 7397 patients served as usual‐care controls . The rates of recurrence/progression of probable hr‐HPVs and lr‐HPVs were not different. Additionally, none of the patients had shown progression to cancer , HPV52 (25.8%), HPV58 (15.6%), HPV33 (6.5%), HPV31 (5.7%), and HPV18 (5.5%), whereas 5.7% of the patients were HPV‐negative. Among HPV‐positive patients (n = 465), 97 (20.9%) were affected by multiple HPV types (Table er Table . The datP = .230)  Figure . The med) Figure .P = .319) , 57 had invasive cancer  Table . The medP = .574) and the 5‐year cumulative rates  was not significantly different   developed concordant type‐specific persistent HPV infections, 37 (44.0%) had discrepant HPV types, and 19 (22.6%) had new HPV genotype(s) . Among the 37 patients with discrepant results, 18 retained original types, although some patients acquired new types, or in some patients, some type(s) disappeared; therefore, type‐specific persistence was 77.4% (65/84) Table . Among tThe time‐dependent HPV infection status distribution of the S group patients is presented in Table 4In our study, the 5‐year cumulative recurrent CIN2+ rate of 14.8% was obtained, which is generally consistent with the rates in our previous studyIn the literature, approximately 5% to 25% of patients developed residual or recurrent disease after conization for HG‐CIN.The median value of HPV persistence tended to decline with increasing follow‐up time up to 24 months,P = .0112).adjusted = 0.86, 95% CI 0.67‐1.09) of recurrent CIN2+ compared to non‐vaccinated patients.Whether HPV vaccination can reduce the future risk of HPV‐related morbidities in patients treated for HG‐CIN has been controversial. However, a retrospective study demonstrated that only 2.5% of patients who received the quadrivalent HPV vaccine after LEEP developed recurrent CIN2/3 compared to 7.2% of those who did not receive the quadrivalent HPV vaccine after LEEP.In our study, we conducted a long‐term follow‐up of HPV genotype changes in relation to the recurrence and progression of HG‐CIN after conization. Our study had the following limitations: (a) The SP group might have had some advantage over the non‐S group because patients who showed progression to invasive cancer during follow‐up were not enrolled into the SP group; (b) many patients were lost to follow‐up in the non‐S group (median follow‐up: 19.8 months); and c) the cutoff of months to exclude non‐S cases with cancer diagnosis from the study was arbitrary; however, this may have inflated the percentage of the persistent HPV genotype among those patients with progression to cancer. Apparently, the cumulative CIN2+ rates were underestimated for both the S and non‐S groups. Another ongoing study using data from the Health and Welfare Data Science Center, Taiwan, will improve the recurrence/progression rate estimation. Additionally, the data on vaginal co‐tests were not analyzed in our study to avoid overwhelming readers and will be reported in a separate paper.In conclusion, the recurrent CIN2+ rate was significantly higher among patients with HPV‐positive results than those with HPV‐negative results in the initial conization samples. Active surveillance might reduce the severity of those progresses to invasive cancer. Emergence of new oncogenic HPV infections is a significant threat; therefore, vaccination against the remaining hr‐HPV types could be included in the care provided to these patients. Because a majority of those with recurrent CIN2+ develop type‐specific persistent HPV infections, effective therapeutic vaccines remains an unmet medical need.The authors declared no potential conflicts of interest.The study was approved by the IRB, and all the S group patients gave their written consent.AppendixS1: Supporting InformationClick here for additional data file.


This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups.  Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), P < 0.001); however, higher infection rates with MH were not observed (P > 0.05). PB, UU, and CT were associated with HR-HPV infection (P < 0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P < 0.05). However, this was not the case for the CT (P > 0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P > 0.05).  The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group ( PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions. Cervical squamous cell carcinoma (SCC) is one of the most common malignant tumors in gynecology . High-grRecent studies have found that certain HPV types and HPV viral loads may be related to HPV infection persistence and cancer progression . In addiThe incidence of lower genital tract infections has been increasing in recent years. An epidemiological survey of women in Beijing, China, showed that 11.4% of women had LGTIs –15. HoweThe aim of this study was to evaluate the prevalence of HR-HPV and other lower genital tract pathogens in different grades of cervical lesions in Fujian, China, and investigate the correlations of coinfection of HR-HPV and lower genital tract pathogens on the risk of high-grade cervical disease.n > 140,000) and had undergone cervical secretion testing, which involved 2 cohorts, one consisting of healthy patients undergoing routine physical examination and the other consisting of patients visiting the outpatient clinic for any gynecologic conditions. All women received cervical secretion testing between January 2012 and January 2016 (n = 1178). The participants were required to meet the following criteria: (1) women in nonmenstrual period; (2) nongestational period, nonlactation period; (3) no acute and chronic illness; (4) no hysterectomy history; (5) no vaginal washing three days before sampling; (6) no use of contraceptives and other vaginal drugs; (7) no previous experience of radiotherapy, chemotherapy, or surgery. The study was approved by the Ethics Committee of Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University (2016-002) and obtained the exemption of informed consent. The study flowchart is shown in The study population was from Fujian provincial lesion screening cohorts , M. hominis (MH), and C. trachomatis (CT).Gynecologists performed routine gynecological examinations. Cervical cytology samples were collected from all subjects using plastic brushes, which were then immersed in a preservation solution for HPV DNA testing, and stored at −20°C. At the same time, cervical samples were collected using sterile cotton swabs for the detection of pathogens Cervical exfoliated cells for polymerase chain reaction-reverse dot blot HPV genotyping  were obtained from all subjects. Twenty-three HPV genotypes were detected, including 18 HR-HPV  and five low-risk HPV  genotypes. All steps were performed in accordance with the manufacturer's instructions, and HPV DNA was amplified in a thermal cycler that included denaturation, annealing, extension, and hybridization. Finally, the blue spots on the strips, which were fixed with the 23 different HPV probes, were identified as positive.2 at 37°C. Individual colonies with large numbers of bacteria were selected, and clinical isolates were identified using standard microbiological methods. VITEK 2 Gram-positive-GP ID and Gram-negative-GN ID cards , based on colorimetric detection, were used for the identification of bacteria according to the manufacturer's instructions. Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, and Enterobacter cloacae ATCC 700323 strains were used as controls.After obtaining the cervical swabs, they were sent to the laboratory immediately. Culture was performed on blood agar plates, chocolate agar plates, and Sabouraud's dextrose agar plates  and incubated for up to 48 h in 5–10% COCervical specimens were collected for UU, MH, and CT testing. UU and MH were isolated by Mycoplasma IST 2 (BioMérieux), using the liquid culture method. Diagnostic criteria were based on the presence or absence of MH and UU and an estimate of concentration variation (cut-off 104-color-changing units-CCU/mL). CT was detected using an immunochromatography assay .P < 0.05 were considered statistically significant.Data were analyzed using SPSS 22.0 . The associations between other lower genital tract pathogens and HR-HPV infection were determined using chi-square tests. To compare the LGTIs positive rates based on pathological diagnosis, chi-square tests or Fisher exact tests were performed. Multivariate logistic regression analysis was used to assess the simultaneous effect of more than one variable on the risk of high-grade cervical lesions and to identify possible confounding factors. Data are reported as numbers (%) or odds ratios (OR) with the corresponding 95% CI. P < 0.001).A total of 458 (51.9%) women were with normal cervical pathology, and 424 (48.1%) women exhibited the following abnormal pathology: 85 LSIL (9.6%), 139 HSIL (15.8%), and 200 SCC (22.7%) . Women wP < 0.001), as shown in P < 0.001, P < 0.001, and P < 0.001, respectively), as shown in P = 0.433) and MH . Multivariate logistic regression analysis suggested that menopausal status, HPV, HR-HPV, PB, UU, and CT were independent risk factors for high-grade cervical lesions , with HR-HPV infection . This was followed by PB , UU , CT , and MH . As expected, as cervical pathology became more severe, the positive rate for HR-HPV significantly increased ( lesions .Escherichia coli (E. coli) . Similarly, UU was detected in 27.2% (125/460) of HR-HPV positive patients and CT in 16.5% (76/460) of HR-HPV positive patients. UU and CT were more likely to be diagnosed in HR-HPV positive women than in those who were HR-HPV negative . The prevalence of MH was 6.7% (31/460) among HR-HPV positive women and 7.1% (30/422) among HR-HPV negative women. Statistical analysis did not reveal any association between the presence of HR-HPV and MH , and a significant association between presence of HR-HPV and PB infection was observed (P < 0.001). Coinfection of HR-HPV and UU increased risk of ≥HSIL . Coinfections of CT plus HR-HPV increased the risk of ≥HSIL . No similar trends were observed in MH.As expected, we found a significant association between PB, UU, CT, and HR-HPV infection, and HR-HPV coinfection with these pathogens increased the risk of high-grade cervical disease. Among them, PB or UU infections may contribute to development of high-grade cervical lesions as an independent risk factor, regardless of whether there is HR-HPV infection. In contrast, we did not find a correlation between MH and HR-HPV or high-grade cervical lesions. In addition, in this study, the distribution of PB flora was also not statistically different between different grades of cervical lesions group.A survey of cervical HPV prevalence in China showed that, among the cervical intraepithelial neoplasia (CIN)2+ patients, the HPV infection rate was 84.97% , which wLactobacillus spp. It contains about 90% of the cervical bacterial flora and serves as the first line of defense against pathogenic bacteria [The healthy cervical bacterial community usually consists of bacteria . More anbacteria . Vaginalbacteria –21. In obacteria . In addiChlamydia trachomatis infection rates are higher in patients with cervical cancer [CT is one of the most widely studied sexually transmitted pathogens. Most epidemiological studies have shown that l cancer –26. Discl cancer . CT infel cancer . CT may In addition, Lukic et al.  found thIn our research population, the prevalence of mixed infections deserves the attention of the public health services. Our study further demonstrates the efficacy of coinfection with HR-HPV and other lower genital pathogens, supporting the high coinfection rate of pathogens, CT, UU, and HR-HPV, and their possible risk in high-grade cervical lesions. Whether it is HR-HPV, pathogens, CT, or UU, the mode of transmission is closely related to sexual intercourse. Therefore, advocating healthy sexual behavior is essential for the prevention and treatment of cervical lesions. It is suggested that, in the screening of clinical SCC and precancerous lesions, in addition to detecting HR-HPV, vaginal microecological detection should be carried out, attention should be paid to the balance of pathogens in the lower genital tract pathogens, and the coinfection of pathogens, CT, UU, and HR-HPV should be screened to block its ability to affect the host's ability to clear HPV infection to determine appropriate diagnostic and therapeutic methods.The advantages of our research include a relatively large number of patients, and the percentage of data missing in patients who participated in the study and met the inclusion and exclusion criteria was small. It is worth noting that our results are based on a summary analysis of rough epidemiological data, with moderate heterogeneity in the study, and without considering risk factors associated with sexual behavior in the study population. In addition, our study is mainly a cross-sectional study, lacking longitudinal observation of HR-HPV and other cervical pathogen infection processes and therefore it is difficult to study the relationship between persistent HR-HPV infection, genital pathogen infections, and cervical lesions. Future prospective cohort studies need to explore their relationship from a vertical perspective.In conclusion, this study provided an opportunity to detect HPV simultaneous detection of pathogens and determine the rate of coinfection between HR-HPV and other lower genital tract pathogens in different grades of cervical lesions. Our results reinforce the hypothesis that some lower genital tract pathogens may be associated with HR-HPV infection and may be a risk factor for high-grade cervical lesions. This study was considered critical to further elucidate the pathogenesis of high-grade cervical disease and to improve early screening and intervention strategies.


Human papillomavirus (HPV) vaccine hesitancy contributes to unsatisfactory vaccination coverage in Korea despite its high efficacy in preventing various diseases including cervical cancer. To enhance HPV vaccine uptake, effective communication with the public is key. To develop effective health promotion messages, this study examined the effects of message format on attitudes and intentions toward HPV vaccination, specifically focusing on anticipated action and inaction regrets. It employed a randomized experimental message design format (narrative versus didactic messages). A total of 222 Korean undergraduate students who had not received the HPV shot participated in the experiment. The results showed that didactic messages produce greater anticipated inaction regret, which further influences HPV vaccination attitudes and behaviors. Anticipated regret could potentially explain mixed narrative effects across health behaviors as described in existing literature. Human papillomavirus (HPV) is one of the most pervasive sexually transmitted diseases and can develop into cervical and anal cancers . In 2012To this end, the present study focused on the relative effectiveness of narrative message formats, which have been acknowledged as “a promising set of tools for motivating and supporting health-behavior change”  (p. 789)The present study focused on Asian young adults because HPV vaccination coverage is much lower in Asia (1.1%) compared to other continents  . MoreoveNarrative, defined as “a representation of connected events and characters that has an identifiable structure, is bounded in space and time, and contains implicit or explicit messages about the topic being addressed”  (p. 222)In the context of vaccination, narrative effects are more obscure and related research has therefore produced even more mixed results than in other topic areas. For example, Hopfer’s longitudinal study  featurinIn contrast, Kim and Nan presented opposing results in an experimental study . They exNan et al.’s experiment with college students also produced null effects, showing no significant differences between narrative and non-narrative texts promoting the HPV vaccine . These nHypothesis 1 (H1).A didactic message produces more positive attitudes toward HPV vaccination than a narrative message.Hypothesis 2 (H2).A didactic message produces greater intentions toward HPV vaccination than a narrative message.Regret, “an aversive cognitive emotion”  , while anticipated inaction regrets occur when one imagines not performing a given behavior . As individuals attempt to reduce self-blame after engaging in or avoiding certain behaviors, non-narrative messages—which rely on the credibility of medical authorities—are expected to be more effective than narrative messages—which are commonly presented by laypersons—in increasing anticipated inaction regrets. Anticipated action regrets, on the other hand, are expected to be more effective when the messages are presented by laypersons since individuals may think of possible procedural risks such as side effects [When making health-related decisions, individuals forgo situations that would have resulted from their alternative decisions and feel responsible for the choices that lead to negative outcomes . Anticip effects . Thus, tHypothesis 3 (H3).A didactic message produces greater anticipated inaction regrets for not getting the HPV vaccine than a narrative message.Hypothesis 4 (H4).A didactic message produces less anticipated action regrets for getting the HPV vaccine than a narrative message.It is further postulated that non-narratives have indirect effects on vaccinating attitudes and intentions via anticipated regrets since anticipated regrets are a critical predictor of HPV vaccination behavior ,35. For Hypothesis 5 (H5).Message format has an indirect effect on attitudes through anticipated inaction regrets.Hypothesis 6 (H6).Message format has an indirect effect on intentions through anticipated inaction regrets.Hypothesis 7 (H7).Message format has an indirect effect on attitudes through anticipated action regrets.Hypothesis 8 (H8).Message format has an indirect effect on intentions through anticipated action regrets.To determine sample size, G*Power  was usedM) age was 21.22 years  and 53.2% of participants were females. Participation was voluntary and no rewards  were provided. The HPV vaccine has been approved for both males and females aged 9–26 [For this study, 222 undergraduate students who had not received any HPV shots were recruited from communication classes at a major university in Seoul, Korea. The sensitivity power analysis for an ANCOVA based on G*Power  indicateged 9–26 , and thuAn experiment was conducted using a paper-and-pencil survey in classrooms. At the end of various classes, the researcher briefly introduced the study to the students and stated that their participation was voluntary. Those who were unwilling to take part in the survey left the classroom and those who were willing to take part remained and received the survey. Study participants first answered some questions regarding HPV and the HPV vaccine. They were then assigned to one of two experimental conditions: 112 participants were assigned to the didactic condition while 124 were assigned to the narrative condition. After reading the stimuli, they answered the survey questions regarding their anticipated regret, attitudes, intentions, and demographic information. A total of 15 surveys were excluded because they were either incomplete or marked repeatedly with the same number from the scale. Therefore, the final sample size was 221 (105 in the didactic condition and 116 in the narrative condition). The researcher obtained informed consent from the participants and endeavoured to comply with ethical standards for treating participants and conducting research, although the institution to which the researcher belonged while collecting data did not require such processes.Two experimental stimuli were adapted from a prior study of narrative health messaging . Each meThe message format (narrative vs. didactic) was manipulated in the last paragraph of each message. The didactic message stated: “The HPV vaccine works effectively to protect your body. Imagine the huge sense of relief you will feel after you have received the HPV vaccine!” Meanwhile, the narrative message stated: “‘I know the HPV vaccine works effectively to protect my body,’ said Yena, a University of X student who recently got vaccinated against HPV, ‘after I got the HPV vaccine, I felt a huge sense of relief!’” Anticipated regret, the extent to which one anticipates negative emotional consequences, was measured twice in relation to either acting  or not acting . Three items adapted from prior research ,41 were Attitudes toward the HPV vaccination were measured using three items. Participants were asked to rate their responses on three 7-point semantic differential scales  to the statement “Getting vaccinated against the human papillomavirus (HPV) is, …” Intentions were measured using two scenarios: (1) the vaccine is offered free of charge and (2) the vaccine costs approximately $440. Intentions toward the HPV vaccination when offered for free were measured using three items. Participants were asked to envision themselves in a situation in which the HPV vaccine was offered for free and then to rate their responses on a 1–7 scale  to the following three questions: “How likely would you be to get the HPV vaccine in the future?”, “How likely would you be to get the HPV vaccine sometime soon?”, and “If you were faced with the decision of whether to get the HPV vaccine today, how likely is it that you would choose to get the vaccine?”. Intentions toward the vaccine with cost were measured with the same three items, after participants were asked to envision themselves in a situation in which they needed to pay $440  to get the vaccine. These measures were adapted from past studies ,42,43.M = 4.86, SD = 1.37; narrative condition M = 4.29, SD = 1.46; p = 0.003) and narrative message as more focused on experience-based description .For manipulation checks of the didactic and narrative message formats, an ANOVA was conducted. The results showed that the participants perceived the didactic message as more explanatory , intentions regarding the free vaccine , and intentions regarding the paid vaccine  only via anticipated inaction regret. Specifically, non-narratives increased anticipated inaction regrets (p = 0.023), which in turn significantly increased attitudes (p = 0.000), intentions regarding free shots (p = 0.000), and intentions regarding paid shots (p = 0.000). Thus, H5 and H6 were supported.H5 and H6 examined the indirect effects of message format on attitudes and intentions through anticipated inaction regrets. To test these hypotheses, Preacher and Hayes’s PROCESS  with 500p = 0.000). p = 0.002), attitudes (p = 0.034), and intentions regarding the free shot (p = 0.048). Gender did not predict any of these variables.H7 and H8 examined the indirect effects of message format on attitudes and intentions through anticipated action regrets. The same procedure using PROCESS  was emplThis is one of the first studies to focus on anticipated regrets as potential mediators in explaining narrative effects on HPV vaccination. Compared to narratives, non-narratives generally produced more positive attitudes toward HPV vaccination. Moreover, this effect occurred through anticipated inaction regret. The findings regarding message format support prior research  showing The present study showed that message format has indirect effects on attitudes and intentions only via anticipated inaction regret. In particular, message format did not yield a direct effect on intentions, but it did have an indirect effect on intentions via anticipated inaction regret. Prior studies have shown that inaction regret is stronger than action regret in vaccination contexts , since pThe associations between message format and anticipated regret may provide the key to explaining narratives’ mixed effects. Generally, narratives have been found to be more effective than non-narratives. However, in HPV vaccination contexts, the effectiveness of narratives has been proven to be null and/or non-narratives have been found to be more effective, as confirmed in this study. Anticipated regrets arise in response to lost opportunities that may have improved particular situations. The choice of forgoing the HPV vaccine, compared to other health behaviors , is expected to incur higher levels of self-blame since it eliminates the opportunity to prevent cervical cancer by 70%. Forgoing other health behaviors may not be perceived as resulting in as much loss as forgoing the HPV vaccination. Simply put, individuals may anticipate more regret from performing or not performing behaviors that are widely perceived to protect health rather than behaviors have uncertain health outcomes.For behaviors involving predetermined consequences, non-narratives delivered directly by medical authorities may be more effective because defying medical authorities’ recommendations can lead to significant losses in health protection. Moreover, in these cases, individuals become more vulnerable to self-blame for not complying with the recommended behaviors. For behaviors involving less predetermined consequences , individuals may doubt didactic information since the potential lost opportunities are less concrete. Therefore, individuals may become more receptive to other laypersons’ narratives, boosting narratives’ relative efficacy. Specifically, in this study, narratives provided by peers may have induced fewer anticipated regrets by being perceived as less credible, while non-narratives may have increased individuals’ expected self-blame via the perception that they were presented directly by medical experts. Although the reasons underlying mixed narrative effects cannot be fully explained, the findings of this study suggest a potential explanation for such effects and highlight the need for further research.This study’s findings need to be interpreted with a few limitations in mind. First, the sample was comprised of college students who are not representative of young adults. This sample may have been above average in terms of young adults’ socioeconomic status. The high cost of the HPV vaccine is one of the major barriers to vaccine uptake . Future Despite these limitations, the findings of this study have several implications for HPV vaccine promotion message design. First, the results indicate that non-narratives are more effective than narratives in promoting HPV vaccination when the messages are presented in print form. They also show that narrative effects are mixed in this context, so health communicators should use narratives cautiously. Second, anticipated inaction regret—through which non-narratives exert their effects—was identified as an important determinant of vaccination behaviors. Health communicators could highlight the lost opportunities for cancer prevention in developing their promotional messages. In particular, the current study revealed that non-narratives affect intentions only via anticipated inaction regret. Therefore, health communicators need to strategically design messages to maximize anticipated inaction regrets. Lastly, this study’s findings regarding message format and anticipated regret can be generalized to other vaccination contexts, although further research would be required. The degree of other vaccines’ disease preventability may differ, but presenting specific information about lost opportunities for health protection by forgoing a vaccine may help enhance the effectiveness of health messages.This study, by examining the relative effectiveness of narrative (versus didactic) messages on attitudes and intentions toward HPV vaccination, enhances our understanding of message format effects. As the first study to focus on anticipated inaction and action regrets, through which message format exerts its effects on vaccine uptake, this study advances scholarly knowledge of the underlying psychological processes of narrative effects. The findings provide practical implications for designing strategic messages for HPV vaccination.


Lactobacillus  is generally supported. On the other hand, high microbial diversity and specific microorganisms such as Sneathia, Anaerococcus tetradius, Peptostreptococcus, Fusobacterium and Gardnerella vaginalis were found to be implicated with higher frequency and severity of disease, potentially resulting in pre-cancerous and cancerous cervical lesions.The role of vaginal microbiota appears to play an as yet not fully understood role in the susceptibility to HPV infection and its natural history.Accumulating evidence indicates the potential correlation between the vaginal microbioma and the acquisition and persistence of human papillomavirus (HPV) infection. This study aims to demonstrate the potential relationship through a systematic review of the current literature. A search was conducted on the following medical databases: PubMed and Scopus. Nineteen studies met the inclusion criteria and were incorporated in the present review. A total of 12.204 patients and their demographic characteristics were studied. Commercially available DNA tests and polymerase chain reaction (PCR) were used for the detection of different HPV subtypes, while the identification of the microbiomes was performed through specific diagnostic methods and PCR assay. The most frequently encountered species were classified based on their protective or detrimental impact on the progression of HPV infection. The beneficial role of some types of  Sexually transmitted diseases (STDs) are among the most frequent infectious diseases worldwide and are defined as those which include transmission of infectious organisms between sex partners. According to the Centers for Disease Control and Prevention almost 19 million cases are reported as infected each year by more than 20 different STDs (Human papillomavirus (HPV) represents one of the most frequent causes of STDs in women around the world . More thThe viral types of HPV can be easily transmitted from one person to another via skin and mucous membranes, which makes the possibility of infection from HPV relatively common. Nevertheless, the majority of infections are subclinical and transient, as they are suppressed by immunocompetent immune systems . TherefoLactobacillus species. In women, whose vaginal microbiota is not lactobacilli-dominated, anti-bacterial defensive mechanisms are decreased  were described by Ravel et al. (Lactobacillus crispatus (L. crispatus), Lactobacillus gasseri (L. gasseri), L. iners and Lactobacillus jensenii (L. jensenii). respectively. In contrast, CST IV is characterized by depletion of lactobacilli and increased diversity of anaerobic bacteria, such as Atopobium  and (HPV or human papillomavirus). The references of relevant articles were also hand-searched, for additional studies.Studies reporting data on the association of microbiota and HPV were included in this systematic review. Abstracts in scientific conferences, editorials, and reviews as well as animal studies were not included in the study. Studies published in languages other than English, Dutch, German, Greek, Italian or Spanish were not taken into consideration.A total of 78 and 291 articles were retrieved from PubMed and Scopus respectively. From those studies, 16 studies were identified as eligible for inclusion in this review. No additional studies were identified through hand-searching of references. The included studies are graphically presented in From the eligible articles, the techniques that were used for HPV detection and the identification of species present in the microbiome were DNA tests, Sequencing and polymerase chain reaction (PCR) amplification.HPV detection and genotyping was performed either with commercially available DNA tests, such as Roche Linear Array HPV Genotyping test and Digene Hybrid Capture II DNA test, or through an assay of PCR using specific primers such as MY09/MY11 or GP5+/GP6+. A range of 15-49 HPV types was identified, including predominantly high-risk HPV types with or without low risk subtypes ,14.For the detection of vaginal microbiota, the initial assessment included diagnostic methods such as microscopic evaluation, Gram stain test, microbiological cultures and measurement of vaginal pH. Amsel criteria were used for diagnosing bacterial vaginosis . PCR ampSixteen studies, including a total of 12.204 patients, have been published in the literature with regard to the association between vaginal microbiota and HPV infection ,32,33,34According to the searched literature, participants were categorized based on several epidemiologic criteria which included age, race/ethnicity, educational status, marital status, time of first intercourse, lifetime number of sexual partners, number of live births, use of hormonal contraception or antibiotics/probiotics, prevalence of smoking, alcohol use, and menstrual phase.Concerning specific population characteristics, the correlation between HPV infection and vaginal microbiota has been studied in human immunodeficiency virus (HIV) infected patients ,28, whilThe demographic details of the populations under study are shown in L. iners classified as CSTIII ; L. crispatus classified as CSTI ; CSTIV-B which represents anaerobic microbiomes combined with reduced Lactobacillus ; Megasphaera, G. vaginalis and L. jensenii which is classified as CSTV ; Sneathia, L. gasseri classified as CSTII as well as CSTIV-A which represents Peptoniphilus, Anaerococcus, Corynebacterium, Finegoldia and Prevotella ; Prevotella, L. vaginalis, Phylum protebacteria, Lactobacillus reuteri (L. reuteri) and other members of Pseudomonas family ; and in one study each (6.25%) Dialister, L. formicalis, Fusobacterium, Lactobacillus gallinarum and Lactobacillus salivarus (found only among South African women).The detected microbiotas in these studies included several types of microorganisms: Lactobacillus. A lower prevalence of L. iners and L. crispatus was also observed (L. crispatus. Other common microorganisms among HPV (+) patients were L. gasseri and Gardnerella vaginalis  also had a high diversity of their vaginal microbiota  and theyorganism . Interesorganism  found anL. crispatus/CSTI and L. gasseri/CSTII were the most common species  women,  species . L. criss et al.  and Borgs et al.  to decreotrichia ,22.The relationship between vaginal microbiota and HPV remission was highlighted by Brotman et al. . CSTIII Brotman et al.  comparedConcerning the severity of the HPV infection, Mitra et al.  reportedL. crispatus was found to have an advantageous effect on the HPV infection evolution in both HIV-infected and uninfected women and in general L. crispatus was found to be a protective factor against HIV, high risk HPV and Herpes Simplex type 2, as it was found in high abundance in uninfected women while, in contrast, infected women had a reduced prevalence. In both HIV and HPV infections, a comparable shift in the composition of the Lactobacillus flora was identified.Five of the above mentioned studies have shown an association between vaginal microbiota, HPV and HIV infection. Another factor that strongly affects the vaginal microbiota seems to be ethnicity. The studies included in this review refer to women of all ethnicities: European/Caucasian, Asian, Latin-American and African. It has been found that Afro-Caribbean women have a fourfold higher risk of suffering from a vaginal dysbiosis or high microbiota diversity, which indicates that the most common type of microbiota among them is CST IV, in comparison with European/Caucasian and African women. However, the prevalence of HPV and the rate of more severe lesions was not proportionately higher .Sneathia, were identified as a possible microbiological marker correlated with HPV infection, as was shown by Lee et al.  low concentration of Lactobacillus and the subsequent vaginal dysbiosis were found to affect the incidence, persistence and severity of HPV infection. The aforementioned parameters should be subjected to further investigation via multicentre trials in order to be validated as robust independent risk factors.Recently available data suggest a potential association between the vaginal microbioma and HPV infection. Specifically, (i) highly diverse vaginal flora, (ii) identification of specific species such as


Stomach adenocarcinoma (STAD) is one of the most common malignancies worldwide with poor prognosis. It remains unclear whether the prognosis is associated with somatic gene mutations.In this research, we collected two independent STAD cohorts with both genetic profiling and clinical follow-up data, systematically investigated the association between the prognosis and somatic mutations, and analyzed the influence of heterogeneity on the prognosis-genetics association.Typical association was identified between somatic mutations and overall prognosis for individual cohorts. In The Cancer Genome Atlas (TCGA) cohort, a list of 24 genes was also identified that tended to mutate within cases of the poorest prognosis. The association showed apparent heterogeneity between different cohorts, although common signatures could be identified. A machine-learning model was trained with 20 common genes that showed a similar mutation rate difference between prognostic groups in the two cohorts, and it classified the cases in each cohort into two groups with significantly different prognosis. The model outperformed both single-gene models and TNM-based staging system significantly.The study made a systematic analysis on the association between STAD prognosis and somatic mutations, identified signature genes that showed mutation preference in different prognostic groups, and developed an effective multi-gene model that can effectively predict the overall prognosis of STAD in different cohorts. Stomach adenocarcinoma (STAD) represents the global fifth most common malignancy and the third leading cause of cancer mortality, with estimated 1,033,701 newly diagnosed cases and 782,685 deaths in 2018 . ScreeniMulti-omics studies disclosed a high heterogeneity of STADs in genetics , gene exFor a variety of tumors, prognosis has been reported to be associated with somatic gene mutations . Despitep-values for each round  mutation rate difference and with recurrent mutations in either group were retrieved as candidate features.Two strategies were adopted for the feature extraction in this research, j m belonging to a certain category Ci, where i equaled to 1 or 0, and mi represented the total number of cases of the category Ci, the genetic features were represented as a binary vector Fj  in which gk  represented the kth genetic feature, taking the value of 1 if the corresponding gene was mutated and 0 otherwise. There was an i∗nm matrix for category Ci. When stage was used as an additional feature, the size of the matrix was enlarged to mi∗(n + 1), and the stage feature was also represented in a binary form in the additional column, for which 1 and 0 represented “early” and “later,” respectively. The anatomic sites were represented as two-bit features, i.e., “cardia/gastro-esophagus junction,” “fundus/corpus,” and “antrum/pylorus” being represented as “00,” “01,” and “10,” respectively.For each case, 1. During the training stage, all four kernels, “Radial Base Function (RBF),” “linear,” “polynomial,” and “sigmoid,” were tested and the parameters were optimized based on a 10-fold cross-validation grid search. The best kernel with optimized parameters was selected for further model training.An R package, “e1071,” was used for training SVM models using each training datasetA 5-fold cross-validation strategy was used in this study. The original feature-represented matrix for each category was randomly split into five parts with identical size. Every four parts of each category were combined and served as a training dataset while the rest one of each category was used for testing and performance evaluation.The Receiver Operating Characteristic (ROC) curve, the area under the ROC curve (AUC), Accuracy, Sensitivity, Specificity, and Mathews Correlation Coefficient (MCC) were utilized to assess the predictive performance. In the following formula, Accuracy denotes the percentage of both positive instances (“good prognosis”) and negative instances (“poor prognosis”) correctly predicted. Specificity and Sensitivity represent the true negative rate and true positive rate, respectively, while the default threshold value from “e1070” (0.0) was used to define the Sensitivity and Specificity in the research. An ROC curve is a plot of Sensitivity versus (1 – Specificity) and is generated by shifting the decision threshold. AUC gives a measure of classifier performance. MCC takes into account true and false positives and false negatives and is generally regarded as a balanced measure which can be used even if the classes are of very different sizes.1. The Gehan–Breslow–Wilcoxon test was used to compare the difference of overall survival curves, and the significance level was set as 0.05.The follow-up survival information of STAD cases was annotated. To evaluate the survival of prediction results of each model, all the 5-fold cross-validation testing results were collected and grouped, followed by the survival analysis for each predicted group. Kaplan–Meier overall survival analysis was performed with R survival packageBoth Tumor Mutation Load (TML) and Missense TML were analyzed for STAD cases of different prognostic groups. TML is defined as logarithm transformation of mutation rate per megabase, while Missense TML only counts the mutations causing amino acid changes. The Wilcoxon rank-sum test was performed to compare the distributions of TML or Missense TML, with the preset significance level as 0.05.TTN, PCDHAC2, PCDHGC5, TP53, MUC16, SYNE1, and CSMD (p < 0.05), while 5 genes showed marginally significant somatic mutation rates among different anatomic sites   .p < 0.20) , area under the receiver operating characteristic (ROC) curves (AUC), and Mathews Correlation Coefficient (MCC) of 0.81, 0.82, and 0.64, respectively (p = 3e-07).The overall survival of the included TCGA STAD cases appeared poor, with a median of 805 days . The cas < 0.20) . A randoectively . Cases cp > 0.05). Distribution analysis on clinical factors of the training cases demonstrated that clinical TNM stage could be a significant co-founding factor (p = 7e-08). The models further integrated with other clinical information-based features , however, performed not better than f52s (To test whether the observed mutation–prognosis association was biased by tumor mutation load (TML), we compared the TML distribution between the cases with good and poor prognosis. However, neither total TML nor missense TML showed significant difference between the two groups of cases either classified by the median survival time or predicted by the f52 model . Other performance measures further demonstrated the superiority of multi-gene models over the individual MUC16 model  between poor and good prognostic groups stratified by 1 year, and observed the mutation rate changes along with overall survival time . The resp = 0.03). Compared to f52, f1y24 did show better performance for the short-term prognosis classification (p = 1e-05).The above results suggested that these gene mutations could be indicators for poorest prognosis. As validation, we used these genes as features and trained models based on 1-year-stratified TCGA training data . The 5-ffication . CombinaThe overall survival of the Chinese cohort with 78 STAD cases appeared better than the TCGA cohort, with a median of 1353 days . We alsoTo our surprise, the Chinese and TCGA cohorts showed an unexpected heterogeneity on the prognosis-associated gene mutation signatures. Very few common genes were identified in both cohorts with either higher or lower mutation rates in good prognostic groups .This dramatic genetic heterogeneity could likely make the TCGA-based prognosis prediction models ineffective in application for the Chinese cohort. The application of the f52, f1y24, and f76 models confirmed the following assumption: none of them could well classify the Chinese cases into groups with different prognosis  and 20 genes showing ≥15%, ≥10%, and ≥5% mutation rate differences between prognostic groups for both cohorts with the same direction (p = 0.008). The model appeared much more effective in prognosis prediction of the Chinese cohort (p = 4e-06). It consistently showed good performance to predict the different stratifications of prognosis for the Chinese cohort, especially for 3- and 2-year prognosis  between prognostic groups for both cohorts stratified, respectively, and the common ones were further identified correspondingly to serve as signatures. To reduce the biases caused by imbalanced sample size between groups, the prognostic groups were stratified by an overall survival period of 576 days for the TCGA cohort and 3 years for the Chinese cohort, respectively, with which the two groups in either cohort showed the identical sample size. There were 0, 4 (irection . Furtherrognosis .p = 4e-06). When testing in the Chinese cohort, however, the performance deteriorated, in spite that it remained effective to predict the prognosis (p = 4e-06). Both cf20 and cf20s, however, outperformed the single-gene models in predicting the prognosis of the STAD cases  could well classify the cases into two groups with significantly differentiated survival . It is nIt was noted that all the 52 genes with most significant difference showed higher mutation rates in the good prognosis group of TCGA cases stratified by the median survival time . It was With the analytic strategy in this study, we also got an interesting finding that the composition of genes and the direction of mutation rate difference between groups stratified by 1-year survival were totally different from those identified for median (573-day) or 2-year stratification . The latHeterogeneity of STADs and their genetics was not surprisingly identified between cohorts, and yet the dramatic difference of prognosis-associated genetic signatures between the TCGA and Chinese cohort was unexpected . Direct Besides somatic mutation signatures, germline variants could also be associated with tumor prognosis. Recently, Milanese et al. reported different germline variants in recurred and non-recurred patients of breast cancers . These sThe datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/YW, XC, and DL conceived the project. XL, XH, and YW coordinated the project. XH, HK, QF, and AC collected the data. XL, XH, HK, YH, and YW performed the analysis. XH, HK, and YW developed the models. XL, XH, HK, and YW wrote the first draft. XL, XH, HK, DL, XC, and YW revised the manuscript. All authors approved the final version of manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Infections by both human oncoviruses, human Papillomaviruses (HPV) and Epstein–Barr virus (EBV) are very common in the adult human population and are associated with various malignancies. While HPV is generally transmitted sexually or via skin-to-skin contact, EBV is frequently transmitted by oral secretions, blood transfusions and organ transplants. This study aims to determine the prevalence and circulating genotypes of HPV and EBV in healthy blood donors in Qatar.We explored the co-prevalence of high-risk HPVs and EBV in 378 males and only 7 females blood donors of different nationalities  residing in Qatar, using polymerase chain reaction (PCR). DNA was extracted from the buffy coat and genotyping was performed using PCR and nested-PCR targeting E6 and E7 as well as LMP-1 of HPV and EBV, respectively.We found that from the total number of 385 cases of healthy blood donors studied, 54.8% and 61% of the samples are HPVs and EBV positive, respectively. Additionally, our data revealed that the co-presence of both high-risk HPVs and EBV is 40.4% of the total samples. More significantly, this study pointed out for the first time that the most frequent high-risk HPV types in Qatar are 59 (54.8%), 31 (53.7%), 52 (49.1%), 51 (48.6%), 58 (47%) and 35 (45.5%), while the most commonly expressed low-risk HPV types are 53 (50.6%), 11 (45.5), 73 (41.7%) and 6 (41.3%), with all the cases showing multiple HPVs infection.In this study, we demonstrated for the first time that HPV and EBV are commonly co-present in healthy blood donors in Qatar. On the other hand, it is important to highlight that these oncoviruses can also be co-present in several types of human cancers where they can cooperate in the initiation and/or progression of these cancers. Therefore, more studies regarding the co-presence of these oncoviruses and their interaction are necessary to understand their cooperative role in human diseases. TP53 and RB expressions, which are known as tumor suppressor genes [Human Papillomaviruses (HPVs) and Epstein–Barr virus (EBV) are human oncoviruses that can co-exist together. HPVs are small, double-stranded DNA viruses which tend to infect cutaneous and mucosal epithelial tissues of the ano-genital tract . HPVs aror genes . Additioor genes –9. On thor genes . Severalor genes –15.Human herpesvirus 4, commonly known as Epstein–Barr virus is a DNA lymphotropic herpesvirus that causes infectious mononucleosis . EBV comSeveral recent studies have demonstrated that the co-presence of high-risk HPVs and EBV mRNA in various human malignancies including cervical, breast and oral cancers, indicating their active role in cancer initiation and metastatic progression via the acceleration of EMT through numerous common signaling pathways , 31.In light of these findings, the objective of this study is to explore the presence of HPV and EBV DNA in the blood of healthy individuals in the Middle East region, more specifically in Qatar.A total of 385 whole blood samples  were collected in EDTA tubes from healthy donors at the Blood Donor Unit of Hamad Medical Corporation (HMC) over a period of 1 year (September 2014–September 2015) as previously described . Blood sDNA was extracted from PMNCs (buffy coat samples) suspended in 200 μl of PBS using Qiagen kit following the manufacturer’s instructions  as previously described . The conTwenty-five nm of purified genomic DNA , from each sample, was analyzed for HPV and EBV by polymerase chain reaction (PCR) using specific primers as follows:The E6/E7 and L1 region of HPV types; GP5/6, 6, 11, 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73 and 82 were amplified  version 25 software (IBM SPSS).Of the total 385 blood samples analyzed in the present study, 378 samples (98.1%) were from males and seven samples (1.8%) from females. The majority of the samples were obtained from non-Qatari residents 66.2%), and the rest were from Qatari individuals (33.7%). The age of participants ranged between 19 and 68 years, (37.12 ± 9.3 years). Based on the study conducted previously , of the %, and thWe herein explored the presence of low-risk HPVs in healthy blood donors from Qatar, in both EBV positive and negative groups. Table Analysis revealed that of the total 385 samples, 235 were positive and 150 were negative for EBV. On the other hand, 233 of the total samples (60.5%) were positive for low-risk HPVs, and all of the positive cases were infected with more than one type of low-risk HPV . However, in EBV-positive samples, as shown in Table Viral infections are the most common etiologic causes of infection-related cancer agents (~ 15%) , 42. AltIn the present study, we investigated the co-presence of both low- and high-risk HPVs and EBV in the blood of healthy individuals from the middle east region, more specifically in Qatar. Several previous studies have already shown the occurrence of HPVs in subjects with unidentified HPV-related disease or cancer; viral DNA/RNA being identified in several tissues including sperm cells , 48, plaAdditionally, based on few studies, HPV DNA was shown to circulate in the bloodstream during ephemeral asymptomatic infections –55; howeOur study has some limitations: Given that it included a very low number of female participants due to socio-cultural factors and religious/fatalistic barriers, in addition to low levels of hemoglobin in women which is reported as a cause of donor loss –60, it iOn the other hand, our present study showed for the first time the co-presence of high and low-risk HPVs with EBV in 40.4% and 50.6% of the examined samples, respectively. More specifically, in EBV-negative samples, approximately more than half of the Qataris were positive for low-risk skin HPV-types HPV-6, 11, 53 and 73 (Table Our study provides evidence that HPV and EBV can be detected and quantified in blood samples of healthy blood donors without any obvious HPV infection, suggesting potential viral persistence at different anatomical sites. This random distribution of HPV subtypes along with EBV, suggests potential facilitative or competitive interactions among these onco-viruses, which has been recently reported by several studies , 46, 66.In conclusion, our study revealed that both low-risk and high-risk HPVs are frequently co-present with EBV among healthy blood donors in the heterogeneous population of Qatar. Further observational and clinical studies are required to assess the full relevance of the obtained data.


Military service during early life can result in exposure to traumatic events that can reverberate throughout life. Although much attention is focused on the negative effects of military service, many veterans report positive effects. These papers explore life course effects of military service on veterans’ health and well-being. Three used national US longitudinal cohorts ; two sampled veterans from Oregon or from Korea. Three compared veterans to non-veterans; two examined veterans only. Cheng and colleagues found that veterans in HRS are more likely to be risk-averse than non-veterans. Risk aversion matters because it determines how people make decisions and predicts a wide array of health and economic outcomes. Kurth and colleagues examined Oregon veterans from several wars, finding PTSD symptoms were highest among Vietnam combat veterans, the oldest cohort; there were no differences among non-combat veterans. Piazza and colleagues examined in MIDUS the impact of veteran status on cortisol, a stress biomarker, finding older veterans more likely had non-normative patterns than did younger or non-veterans. Lee and colleagues studied patterns of mental health among Korean Vietnam veterans, identifying two patterns as ‘normal’ and ‘resilient’ encompassing half the sample; these veterans demonstrated positive outcomes of military service. Frochen and colleagues compared depression trajectories between veterans and non-veterans in HRS, finding veterans had less depression than non-veterans, but among veterans, trajectories varied based on extent of service. in sum, these papers demonstrate that military service can have positive as well as negative effects on veterans’ health and well-being in later life. Aging Veterans: Effects of Military Service across the Life Course Interest Group Sponsored Symposium.


This study aims to evaluate the clinical performance of the HPV E6/E7 mRNA test in cervical cancer screening in China. A hospital-based study was conducted with mRNA, DNA, and liquid-based cytology (LBC) as primary screening tests. Each woman with a positive result received colposcopy with lesion-targeted-biopsy. Histopathological diagnosis was used as the gold standard. The total agreement of HPV DNA and mRNA was 90.7%  with a kappa value of 0.81. The positive rates of HPV DNA, mRNA, and LBC increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2+ and CIN3+ were 93.8% (95%CI: 89.7–96.4) and 95.7% (95%CI: 91.3–97.9), respectively, which were not different from HPV DNA testing , but higher than LBC (80.4% [95%CI: 74.5–85.2] and 88.8% [95%CI: 83.0–92.8]). The specificities for mRNA to detect CIN2+ (79.0% [95%CI: 74.2–83.0]) and CIN3+ (70.5% [95%CI: 65.7–74.9]) were higher than HPV DNA testing , but lower than LBC (84.5% [95%CI: 80.1–88.0] 79.8% [95%CI: 75.4–83.6]). All tests were more effective in women older than 30 years. HPV mRNA test showed excellent agreement with the DNA test, with similar sensitivity and a higher specificity in detecting high-grade cervical lesions. It is promising that mRNA test could be used for the national cervical cancer screening to reduce false positive without losing sensitivity. It is known that persistent infection with high-risk human papillomavirus (hr-HPV) is a necessary cause for cervical cancer and precancerous lesions , 2. WithIn China, there were 98,900 new cases and 30,500 deaths from cervical cancer in 2015 . To curbDisease-specific molecular markers of cervical cancer provide a combination of high sensitivity and high specificity to detect cervical pre-cancer. Most of these markers were identified based on the mechanism of HPV-related carcinogenesis. The HPV RNA testing is based on the detection of HR-HPV E6 and E7 mRNA. The oncogenic potential of HPV infection depends on the production of viral E6/E7 oncoproteins. Thus, the detection of E6/E7 mRNA transcripts provides the possibility for a specific test to detect precancerous lesions.In this study, we evaluated the clinical performance of the HPV E6/E7 mRNA test to detect high-grade cervical intraepithelial neoplasia (CIN) and cancer among Chinese women.This hospital-based study was conducted during April to December 2017 in Henan province, China. Women who visited the department of gynecology of The Second Affiliated Hospital of Zhengzhou University (SAHZU) for colposcopy were invited. The inclusion criteria were as follows: (1) women aged between 25 and 64 years-old; (2) no history of cervical cancer or hysterectomy; (3) no clinical symptoms of pregnancy or 8 weeks after the termination of pregnancy; and (4) understand the study procedures, and voluntarily participated. The study was approved by the Institutional Review Board (IRB) of Henan Cancer Hospital (HCH). Written informed consent was obtained from each participant.® transport medium  and stored at 4°C. Then, colposcopy examination was performed by a gynecologist. Women with abnormal colposcopy finding underwent lesion-targeted biopsy. If the colposcopy examination was unsatisfactory (the squamocolumnar junction was not completely visible), endocervical curettage (ECC) was performed. Specimens of cervical exfoliated cells were transported to the Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CICAMS). The specimens were divided into two portions: a 1.5 ml cell mixture into a EP tube for the HR-HPV DNA test and HPV E6/E7 mRNA test. The residual preservcyt with exfoliated cells was used for ThinPrep cytologic test (TCT) . The Bethesda reporting system was used for cytology by a senior cytologist  by Cobas 4800 HPV assay . It reported pooled result of the 14 hrHPV, and the separate result for HPV 16 and 18, simultaneously , according to the manufacturer’s instructions . It was Biopsy and ECC tissues were sent to SAHZU for histopathological diagnoses according to the cervical intraepithelial neoplasia (CIN) reporting system. Then histopathologists from HCH reviewed all the slides. Any inconsistent pathological diagnosis was sent to CICAMS for adjudication. The final diagnosis for each woman was based on the worst reading from the panel review. All the detection and diagnosis process were blind.p < 0.05 (two-sized) was deemed as statistically significant.The final histopathological diagnosis was used as the gold standard. Women with TCT diagnosis of the low-grade squamous intraepithelial lesion (LSIL) or worse (LSIL +) were deemed as liquid-based cytology (LBC) positive. The HPV DNA results were stratified, according to the HPV types: HPV16/18 , HPV-others , and HPV-total . The absolute estimates and 95% confidential intervals (95%CI) of positive rates, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. The differences in HPV mRNA expressions in different HPV groups were calculated using the chi-square test or Fisher’s exact test. The McNemar test was used to identify the differences in sensitivity and specificity. The α level was set at 0.05, and in situ (AIS). The histopathology diagnoses were 298 (55.5%) normal, 30 (5.6%) cervical intraepithelial neoplasia grade 1 (CIN1), 48 (8.9%) CIN2, 111 (20.7%) CIN3, 43 (8.0%) SCC, and 7 (1.3%) AIS.In total, 537 women were included in this analysis. The average age was 43.88 ± 10.97 years. The LBC diagnoses were: 183 (34.7%) normal, 135 (25.1%) atypical squamous cells of undetermined significance (ASC-US), 22 (4.1%) atypical squamous cell cannot exclude HSIL (ASC-H), 7 (1.3%) atypical glandular cell (AGC), 82 (15.3%) LSIL, 75 (14.0%) high-grade squamous intraepithelial lesion (HSIL), 31 (5.8%) squamous cell carcinomas (SCC), and 2 (0.4%) adenocarcinoma p < 0.001).The HPV DNA, mRNA, and LBC positive rates increased with the severity of histopathology diagnosis, ranged from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The positive rates of the three tests in AIS were 85.7, 85.7, and 100.0%, respectively. These three tests had similar positive rates in CIN3, SCC, and AIS. But the positive rates of mRNA were relatively lower in women under CIN2 diagnosis. The rates of HPV16 positive were the highest in CIN3, SCC, and AIS when compared with other HPV DNA groups. HPV18 positive rates were lower than 7% in all squamous cell lesions, but a little higher (28.6%) in AIS .p < 0.05), but lower than those detected by LBC . The PPVs for mRNA to detect CIN2+ and CIN3+ were 74.0% (95%CI: 68.4–78.9) and 58.1% (95%CI: 52.1–63.9), and the NPVs were 95.2% (95%CI: 92.0–97.2) and 97.4% (95%CI: 94.8–98.8), respectively.The presented results showed that the mRNA test and DNA teat reached a high agreement as 90.7%. The HPV DNA, mRNA, and LBC positive rates increased with the severity of histopathology diagnosis, from 25.5, 19.1, and 11.4% in normal to 100.0% in SCC, respectively. The sensitivities for mRNA to detect CIN2 and CIN3+ were 93.8% and 95.7%, which were similar to those detected by DNA (95.7% for CIN2+ and 96.3% for CIN3+). But the specificities for mRNA (79.0% for CIN2+ and 70.5% for CIN3+) were significantly higher than those detected by DNA (71.0% for CIN2+ and 62.8% for CIN3+).In this study, the HPV E6/E7 mRNA test and HPV DNA test showed high agreement. Of those HPV 16/18 DNA positive women, 91.7% were also positive on mRNA, which is similar to other studies, that reported an overall agreement of over 90% between APTIMA HPV test and HPV DNA tests , 18, andAs we know, DNA-based HPV tests detect the presence or absence of HPV DNA. However, most HPV infections are transient, cleared spontaneously within 1 year, which would not progress to cervical pre-cancer or cancer . E6/E7 mWe also evaluated the test performance in older and younger women. The age-specific analysis found that the three tests functioned better in women older than 30 years. Based on the fact that younger women with CIN lesions had a higher possibility of regression, we suggest a conservative management of younger women. Studies have found that HPV infection was common in young women, however, a large portion of them were transient infections, and may be cleared spontaneously , 32. TheAlthough the China Food and Drug Administration approved three prophylactic HPV vaccines , cervical cancer prevention still relies on screening. In 2009, the Chinese government launched a nationwide free cervical cancer screening for rural women. In 2015, the HPV DNA test was used as a primary screening tool in pilot sites for the first time. However, due to its large population, HPV DNA-based screening would result in unavoidable huge false positives, leading to a waste of health resources and unnecessary anxiety. It is promising that mRNA could be used in the national cervical cancer screening program to reduce the false positive without losing any sensitivity.Several limitations should be addressed in this study. First, this is a cross-sectional study, and we could not evaluate the risk of lesion progression associated with HPV E6/E7 mRNA. However, we stratified our data by histological grade, which provides information on the correlation. Second, it is important to note that the results cannot be fully generalized to the general population because the study participants were recruited from the outpatient in hospital.In conclusion, the APTIMA mRNA test had good agreement with Cobas 4800 HPV DNA test with similar sensitivity and higher specificity to detect high-grade cervical lesions. It is promising that mRNA could be used in China’s national cervical cancer screening program to reduce the false positive without losing any sensitivity. Further studies are needed to evaluate the clinical performance of mRNA test in younger women in China.All datasets generated for this study are included in the article/supplementary material.The studies involving human participants were reviewed and approved by the role of co-expression of HPV E6/E7 mRNA and p16/Ki-67 protein in predicting the risk of cervical cancer. By Life Science Ethics Review Committee of Zhengzhou University. The patients/participants provided their written informed consent to participate in this study.S-KZ contributed to the design and wrote the manuscript. ZG contributed to the manuscript’s writing and revision. PW, M-MJ, and P-PG contributed to the investigation and HPV DNA test. L-NK and Z-NW contributed the HPV mRNA test. D-MZ contributed to cytology and histology examination. QC and X-QC performed the statistical analysis. X-BS helped to conceive the study and assisted with the statistical analyses. Y-LQ and J-GZ helped to conceive the study and assisted with the manuscript’s writing. J-GZ assisted with the implementation of the study. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This study aimed to investigate how gynecologic oncologists modified their patient management during Coronavirus disease-2019 (COVID-19) in Turkey.An online survey was sent to gynecologic oncology specialists and fellows in Turkey. It included management questions about strategies for newly diagnosed or recurrent endometrial, cervical, ovarian and vulvar cancer during the pandemic. Participants were asked if treatment of these cancers can be delayed or not and, if yes, the duration of delay.32.9% of surgeons prescribed oral or intrauterine progesterone for early stage, low-grade endometrial cancer. Conversely, 65.7% and 45.7% of the most surgeons did not change their management for early stage high-grade and advanced stage endometrial cancers respectively, as they perform surgery. 58% and 67.1% of the surgeons continued to prefer standard surgical treatment for microinvasive and early stage cervical cancers, respectively. Radiotherapy was preferred administered with hypofractionated doses for locally advanced cervical cancer (57.1%). While 67.1% of surgeons operated early stage ovarian cancer patients, 50% administered neoadjuvant chemotherapy (NACT) to all advanced stage ovarian cancers and 50% administered more cycles of NACT in preference to interval debulking surgery. 93.7% of the surgeons responded that treatment should not be delayed beyond eight weeks.Most Turkish gynecologic oncologists modified their management of gynecologic cancers due to the COVID-19 pandemic. While chemotherapy was preferred for ovarian cancer, postponement of the surgery, with or without non-surgical options, was considered for early stage, low-grade endometrial cancer. Treatment of gynecologic cancers should be decided on a case by case basis, taking into account local COVID-19 infection rates and availability of health facilities. Prognosis is also an important consideration if delay is contemplated. Standard treatment and normal time-frames should be used if possible. If not, a postponement for a maximum of eight weeks or referral to another center were acceptable alternatives. At the end of 2019, a novel type of coronavirus, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was identified as the cause of severe pneumonia in China  beds may not be available due to COVID-19. Many organizations and associations issued new guidelines, taking into account the effect of the pandemic, for the management of gynecologic cancers ,3.As of 10 May 2020, 138,657 cases of COVID-19 have been reported in Turkey and cases continue to occur with variable incidence. The Turkish Society of Gynecologic Oncology (TRSGO) has issued its recommendations that management of gynecological cancer patients may differ between centers according to available resources .The aim of this study was to investigate how gynecologic oncologists modified their management of gynecologic malignancies during the COVID-19 pandemic in Turkey.This study was approved by Ordu University Institutional Review Board . A questionnaire developed by the TRSGO was sent to gynecologic oncology specialists and trainees working actively at either university hospitals, training hospitals, public hospitals or special clinics across Turkey via the internet. The survey was sent in April 2020, along with an informed consent form. Respondents were able to complete and return the survey online. The questionnaire included how management of endometrial, cervical, ovarian and vulvar cancer changed during the pandemic. Participants were also asked if treatment of these cancers can be delayed or not and, if yes, the duration of delay.Descriptive analyses are presented as numbers and percentages. Chi-square test and Fisher’s exact test were used to compare clinico-pathologic characteristics. Values of p<0.05 were considered statistically significant. SPSS, version 21.0  was used for statistical calculations.The survey was sent to 172 physicians listed in the TRSGO database. Of these, 70 (40.7%) gynecologic oncologists or fellows in gynecologic oncology answered the survey. As seen in 67.1% of participants did not change their management (staging surgery) in early stage ovarian cancer. If it was not possible to operate, they mostly (12.9%) referred patients to more suitable cancer centers, rather than administering CT after obtaining tissue biopsy. While 38.6% continue to perform interval debulking surgery (IDS) for patients who had already completed their neoadjuvant chemotherapy (NACT), 50% administered more cycles of CT and 11.4% referred patients to another center. 50% of surgeons administered NACT to all advanced stage ovarian cancers, 20% continued to operate, 17.1% limited cytoreductive surgery indication and the remainder either delayed the operation or referred the patients elsewhere. 32.9% of surgeons administered NACT according to cytology, 15.7% performed diagnostic L/S, and 48.6% referred patients to interventional radiology for tissue biopsy. 2.9% administered NACT if there was a very high suspicion of ovarian cancer without confirmation by cytology or tissue biopsy. While 44.3% continued to operate recurrent ovarian cancer patients who were suitable for surgery, 28.6% administered CT and the rest either delayed the operation or referred the patients elsewhere.As seen in Participants were asked to score their priority for treatment of each gynecologic cancer from 1 to 5, with 1 the lowest priority and 5 the highest priority. One participant did not answer this part of the questionnaire. While continuing to be mindful of disease progression, participants were asked their opinion on the maximum time (in weeks) that treatment can be delayed under COVID-19 conditions. As seen in With the rapid spread of COVID-19 throughout the world, national health systems of many counties experienced additional stresses. Many countries, including Turkey, took steps to slow the spread of infection. Much elective surgery was suspended to allow resources to be deployed for COVID-19. Despite this situation, it was apparent that clinicians had a duty to continue to provide health care to gynecologic oncology patients.97.1% of responding Turkish gynecologic oncologists stated their cancer management changed during the pandemic. Surgical treatment remained the gold standard for many types of gynecologic cancers. However, performing surgery may not be possible under pandemic conditions. There are several reasons for this. First, gynecologic oncology patients are generally old and have pre-existing comorbidities such as cardiovascular disease or diabetes mellitus. Therefore, they may need observation in ICU postoperatively. Even a young patient undergoing radical surgery and multiorgan resection may need ICU. Unfortunately, many ICU beds were, and continue to be, occupied by COVID-19 patients. Second, some hospitals ran out of blood and blood products since fewer people made blood donation due to the pandemic. Third, when COVID-19 is more prevalent, COVID-19 patients are hospitalized not only in infectious disease or respiratory disease clinics, but also in any available hospital bed. Many clinics were converted into COVID-19 clinics due to the growing number of infected patients. Lastly, some gynecologic oncologists were recruited to take care for COVID-19 patients ,6.The route of surgery was another change during the pandemic. The majority of surgeons 73.9%) preferred L/T rather than L/S because of concern about viral transmission via contaminated aerosol produced from port sites during L/S. To date, there is no evidence to show that the COVID-19 virus speads via laparoscopic smoke plume and this theoretical risk was extrapolated from other viral infections. For example, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and human papillomavirus (HPV) have been detected in surgical smoke ,6,7,8. A3.9% prefPerforming operations solely using L/T because of this hypothetic risk may result in more surgical complications, such as blood loss, wound infection or atelectasis, longer hospital stay and greater risk of COVID-19 exposure for the patient. Since electrosurgical devices create surgical smoke plumes, they potentially increase viral transmission both in open and minimally invasive surgeries. There is no evidence to prove that infection occurs more often via L/S compared to L/T. Nevertheless, precautions should be taken to minimize this theoretical risk and these should include all operating room personnel being equipped with adequate personal protective equipment, L/S being performed with lower intra-abdominal pressure when possible, use of energy should be minimized and smoke evacuation/filtration should be used ,10. TherOral progesterone or progesterone releasing IUD is the most common management strategy for early stage, low-grade endometrial cancer amongst Turkish gynecologic oncologists and it is a reasonable alternative to surgery. Several studies have reported 75-80% regression rate with oral progestins in young endometrial cancer patients who want to retain fertility ,10,11,12Surgery is the accepted standard of care for early stage cervical cancer. As such, most Turkish gynecologic oncologists continue to operate microinvasive and early stage cervical cancers. If immediate operation was not possible, operations were delayed, since postponing the surgery for 6-8 weeks has been recommended as acceptable for localized disease during the pandemic . Primary67.1% of participants perform staging surgery for early stage ovarian cancer. Performing only adnexectomy and deferring the staging surgery for 1-2 months may be another alternative under pandemic conditions ,13. DespThe majority of surgeons treated both early and advanced stage vulvar cancer as they had done prior to the pandemic. This result is unsurprising since surgery is the only treatment option in many cases. When the tumor is small, it has been reported that it is acceptable to postpone surgery for a couple of months .Time is particularly important in the fight against cancer as the chance of achieving a cure can be lost if if the delay is too long. However, due to the pandemic, delay in treatment is currently unavoidable. Therefore, one should always keep in mind which patients will benefit most from treatment, who needs to be treated urgently and who can wait for some time without disease progression. Participants indicated a general belief that timing of treatment is more important for advanced stage and high-grade tumors compared to early stage and low-grade tumors. Hence, a delay in cancer treatment to minimize infection risk is more commonly associated with early stage cancers compared to advanced stage tumors.This is the first national survey of gynecologic oncologists regarding changes to their practice due to the COVID-19 pandemic. A strength of this study is the inclusion of an homogenous group of gynecologic oncologists who actively work in Turkey. However, as this is a single country survey and only 40.7% of gynecologic oncologists responded, it may limit generalization.Most gynecologic oncologists have changed their management for gynecologic cancers due to the pandemic. While surgery was postponed and progesterone treatment was preferred in early stage low-grade endometrial cancer, CT came to fore for ovarian cancer. Surgery is performed immediately or with a delay for microinvasive and early stage cervical cancers and hypofractionated dose is preferred for LACC. The number of COVID-19 infected patients and availability of health facilities differ from center to center within Turkey. During the pandemic, treatment for gynecologic cancers should be decided on a case by case basis, taking into account local resource availability and local risk of infection, in conjunction with the chance of achieving a cure. The authors believe that, applying standard treatment when possible and, if not, postponing the treatment for a couple of months in patients in whom it is safe to do so or referral to another cancer center when delay is inadvisable are the best choices at the current time.


The recent coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disruption which also extends to the arena of scientific meetings around the world. Here, we explore the lessons learned from moving two human genetics and genomics meetings quickly to an online format in early 2020. The tips presented herein may be useful not only for future virtual meetings but may also enrich future physical if not hybrid meetings once they resume. Both meetings are convened annually or biannually under certain circumstances with attendance around 500 and lasting over several days. The 2020 HGM and G2MC were convened virtually in the first few months of 2020 pivoting quickly from the traditional physical setup. The HGM had 505 attendees from 37 countries and all continents. This included 123 registrants that only registered after the announcement that the meeting would go fully virtual. HGM2020 was planned for in its physical version and hence run from Perth, WA, Australia, in early April of 2020. The G2MC was envisaged for Santiago, Chile, in early May 2020 and accordingly run mostly virtually from Santiago as well, with 489 registrants from 50 countries across all continents, more than doubling the original 176 registrants from 20 countries.Due to the COVID-19 (coronavirus disease 2019) pandemic . The theme of the meeting was Genomic Medicine Implementation in Low Resources Settings-Latin America (LATAM), as a follow-up to the previous meeting with a similar focus that took place in Cape Town, South Africa, in December 2018. In early March 2020, given the global epidemiological situation with the first cases of COVID-19 being diagnosed in LATAM, the decision was made to change the meeting to a virtual modality. The program maintained most of its original structure: parallel, highly interactive working-group sessions on specific projects, followed by sequential presentations by invited speakers organized around specific themes. Nevertheless, several changes were introduced: the overall duration of each day´s program was shortened from the original version to accommodate the diverse time zones of the participants, conferences were reduced in duration to focus on highlights of ongoing programs and initiatives, the time allotted to Q&A sessions was increased to promote interactions, and the decision was made to postpone the Young Investigators´ Forum to a future face-to-face meeting to optimize opportunities for networking. The most significant and immediate effect of the virtual format was the increased number and country of origin of registrants, particularly from LMIC, a result that was aligned with the aims and theme of the meeting. Compared to previous G2MC meetings, the increase of registrants from LATAM was noticeable whilst Africa was also again well represented. The G2MC meeting could pivot earlier in the planning to a virtual setting and accordingly realized substantial cost savings. When comparing the costs of past physical and the 2020 virtual meeting, it is important to also bear in mind that both the HGM and the G2MC are held around the world which leads to varying cost structures.The 5th G2MC meeting was scheduled to occur from May 6–8 2020 in Santiago, Chile [A post meeting survey to participants, 97% declared being “very satisfied or satisfied” with the virtual format. Responders were also satisfied with items related to interaction, such as time allocated for discussion, and opportunities for networking and future collaborations. Over 60% expressed that they would be unable or unsure about participating in a face to face meeting.Other meetings have also gone virtual to notable success  echoing