Both middle and large envelope proteins can mediate neutralization of hepatitis B virus infectivity by anti-preS2 antibodies: escape by naturally occurring preS2 deletions.

Hepatitis B virus (HBV) expresses co-terminal large (L), middle (M), and small (S) envelope proteins containing preS1/preS2/S, preS2/S, and S domain alone, respectively. S and preS1 domains mediate sequential virion attachment to heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP), respectively, which can be blocked by anti-S and anti-preS1 antibodies. How anti-preS2 antibodies neutralize HBV infectivity remains enigmatic. The late stage of chronic HBV infection often selects for mutated preS2 translation initiation codon to prevent M protein expression, or in-frame preS2 deletions to shorten both L and M proteins. When introduced to infectious clone of genotype C or D, both M-minus mutations and most 5' preS2 deletions sustained virion production. Such mutant progeny viral particles were infectious in NTCP-reconstituted HepG2 cells. Neutralization experiments were performed on the genotype D clone. Although remaining susceptible to anti-preS1 and anti-S neutralizing antibodies, M-minus mutants were only partially neutralized by two anti-preS2 antibodies tested while preS2 deletion mutants were resistant. By infection experiments using viral particles with lost versus increased M protein expression, or a neutralization escaping preS2 deletion only present on L or M protein, we found that both full-length L and M proteins contributed to virus neutralization by the two anti-preS2 antibodies. Thus, immune escape could be a driving force for the selection of M-minus mutations, and especially preS2 deletions. The fact that both L and M proteins could mediate neutralization by anti-preS2 antibodies may shed light on the underlying molecular mechanism.IMPORTANCEThe large (L), middle (M), and small (S) envelope proteins of hepatitis B virus (HBV) contain preS1/preS2/S, preS2/S, and S domain alone, respectively. The discovery of heparan sulfate proteoglycans and sodium taurocholate cotransporting polypeptide (NTCP) as the low- and high-affinity HBV receptors could explain neutralizing potential of anti-S and anti-preS1 antibodies, respectively, but how anti-preS2 neutralizing antibodies work remains enigmatic. In this study, we found two M-minus mutants in the context of genotype D partially escaped two anti-preS2 neutralizing antibodies in NTCP-reconstituted HepG2 cells, while several naturally occurring preS2 deletion mutants escaped both antibodies. By point mutations to eliminate or enhance M protein expression, and by introducing preS2 deletion selectively to L or M protein, we found binding of anti-preS2 antibodies to both L and M proteins contributed to neutralization of wild-type HBV infectivity. Our finding may shed light on the possible mechanism(s) whereby anti-preS2 antibodies neutralize HBV infectivity.

5' preS1 Mutations To Prevent Large Envelope Protein Expression from Hepatitis B Virus Genotype A or Genotype D Markedly Increase Polymerase-Envelope Fusion Protein.

Hepatitis B virus (HBV) large (L) envelope protein is translated from 2.4-kb RNA. It contains preS1, preS2, and S domains and is detected in Western blotting as p39 and gp42. The 3.5-kb pregenomic RNA produces core and polymerase (P) proteins. We generated L-minus mutants of a genotype A clone and a genotype D clone from 1.1-mer or 1.3-mer construct, with the former overproducing pregenomic RNA. Surprisingly, mutating a preS1 ATG codon(s) or introducing a nonsense mutation soon afterwards switched secreted p39/gp42 to a p41/p44 doublet, with its amount further increased by a nonsense mutation in the core gene. A further-downstream preS1 nonsense mutation prevented p41/p44 production. Tunicamycin treatment confirmed p44 as the glycosylated form of p41. In this regard, splicing of 3.5-kb RNA to generate a junction at nucleotides (nt) 2447 to 2902 for genotype D enables translation of p43, with the N-terminal 47 residues of P protein fused to the C-terminal 371 residues of L protein. Indeed p41/p44 were detectable by an antibody against the N terminus of P protein and eliminated by a nonsense mutation at the 5' P gene or a point mutation to prevent that splicing. Therefore, lost L (and core) protein expression from the 1.1-mer or 1.3-mer construct markedly increased p41/p44 (p43), the P-L fusion protein. Cotransfection with an expression construct for L/M proteins reversed high extracellular p41/p44 associated with L-minus mutants, suggesting that L protein retains p43 in wild-type HBV to promote its intracellular degradation. Considering that p43 lacks N-terminal preS1 sequence critical for receptor binding, its physiological significance during natural infection and therapeutic potential warrant further investigation. IMPORTANCE The large (L) envelope protein of hepatitis B virus (HBV) is translated from 2.4-kb RNA and detected in Western blotting as p39 and gp42. Polymerase (P) protein is expressed at a low level from 3.5-kb RNA. The major spliced form of 3.5-kb RNA will produce a fusion protein between the first 47 residues of P protein and a short irrelevant sequence, although also at a low level. Another spliced form has the same P protein sequence fused to L protein missing its first 18 residues. We found that some point mutations to eliminate L and core protein expression from overlength HBV DNA constructs converted p39/gp42 to p41/gp44, which turned out to be the P-L fusion protein. Thus, the P-L fusion protein can be expressed at extremely high level when L protein expression is prevented. The underlying mechanism and functional significance of this variant form of L protein warrant further investigation.

Improving the resident assessment process: application of App-based e-training platform and lean thinking.

BACKGROUND: The assessment system for standardized resident training is crucial for developing competent doctors. However, it is complex, making it difficult to manage. The COVID-19 pandemic has also aggravated the difficulty of assessment. We, therefore, integrated lean thinking with App-based e-training platform to improve the assessment process through Define-Measure-Analyze-Improve-Control (DMAIC) cycles. This was designed to avoid unnecessary activities that generate waste. METHODS: Panels and online surveys were conducted in 2021-2022 to find the main issues that affect resident assessment and the root causes under the frame of waste. An online app was developed. Activities within the process were improved by brainstorming. Online surveys were used to improve the issues, satisfaction, and time spent on assessment using the app. RESULTS: A total of 290 clinical educators in 36 departments responded to the survey, and 153 clinical educators used the online app for assessment. Unplanned delay or cancellation was defined as the main issue. Eleven leading causes accounted for 87.5% of the issues. These were examiner time conflict, student time conflict, insufficient examiners, supervisor time conflict, grade statistics, insufficient exam assistants, reporting results, material archiving, unfamiliarity with the process, uncooperative patients, and feedback. The median rate of unplanned delay or cancellation was lower with use of the app (5% vs 0%, P < 0.001), and satisfaction increased (P < 0.001). The median time saved by the app across the whole assessment process was 60 (interquartile range 60-120) minutes. CONCLUSIONS: Lean thinking integrated with an App-based e-training platform could optimize the process of resident assessment. This could reduce waste and promote teaching and learning in medical education.

Online re-examination of postgraduate medical students during the COVID-19 pandemic.

BACKGROUND: Postgraduate entrance examination (the Unified National Graduate Entrance Examination) is the major way for Chinese medical undergraduate student to apply for postgraduate studies. It consists of two stages: the preliminary basic written test and the re-examination in form of both written tests and interviews. With the spread of COVID-19, the traditional on-site re-examination of postgraduates must be changed to online re-examination. By comparing the re-examination process and admission results of online and on-site re-examination, we studied the feasibility of online re-examination for postgraduates and measures to improve it. METHODS: This was a retrospective cohort study using data from the Unified National Graduate Entrance Examination. Our sample population was the applicants to Peking University Third Hospital (PUTH) who completed re-examinations. In total, 281 records were successively selected from March 2017 to May 2020. By comparing the re-examination process and admission results of the 2020 online re-examination with those of the 2017-2019 on-site re-examinations, we analyzed the process, difficulties and improvement of online re-examination. RESULTS: A total of 281 subjects were included, of whom 77.9% completed an on-site re-examination in 2017-2019 and 22.1% completed the 2020 online re-examination. In the on-site re-examinations, 70.8% of the students were admitted, and in the online re-examination, 74.2% of the students were admitted. There were no significant differences between the students who completed on-site and online re-examinations in terms of gender, recent graduation, cultivation type, graduate from a key university, and admission (P>0.05). The on-site and online re-examination results were very similar among the admitted students. The multivariable logistic regression analysis showed that online re-examination had no effect on student admissions. Students seeking professional degree were less likely to be admitted than those seeking academic degree, and those with a better standardized rank in medicine and a better standardized rank of re-examination score were more likely to be admitted. CONCLUSIONS: The online re-examination implemented in 2020 during the COVID-19 pandemic achieved the same selective effect as on-site re-examination. Effective time management, a standardized test question template, well-trained staff and effective technology are the keys to success.

Application of PDCA cycle management for postgraduate medical students during the COVID-19 pandemic.

BACKGROUND: The COVID-19 outbreak has exerted an enormous impact on various industries worldwide. During this pandemic, clinical teaching hospitals have faced unprecedented challenges regarding the management of postgraduate medical students since postgraduate students in clinical medicine have both student and resident identity characteristics. The purpose of this study was to explore the management effectiveness of Peking University Third Hospital (PUTH) based on PDCA (plan-do-check-act) cycle management and to further develop the medical student management system during the pandemic. METHODS: The methods of document review, questionnaire surveys and interviews were used to continuously improve the management measures for postgraduate medical students during the COVID-19 pandemic by using the PDCA cycle. RESULTS: Investigations were conducted on the management system, back-to-school arrangements, laboratory management, COVID-19 prevention and control training, online teaching, mentoring, dissertation progress, and emotional state of postgraduate medical students during the COVID-19 pandemic. We found that strengthening public health management knowledge training, increasing infectious-disease-related knowledge training, innovating online teaching methods, improving PDCA management model maps, and formulating improvement programmes are conducive to improving the quality of such management. CONCLUSION: Given the difficulties involved in the management of postgraduate medical students during the COVID-19 pandemic, managers need to comprehensively consider and conduct overall planning and use the PDCA management model to improve the management of postgraduate medical students during this period.

Clonal evolution of esophageal squamous cell carcinoma from normal mucosa to primary tumor and metastases.

The clonal evolution which drives esophageal squamous cell carcinoma (ESCC) from initiation in normal cell to primary carcinoma and metastases is poorly understood. In this study, multi-region whole-exome sequencing (WES) (284X) and whole-genome single nucleotide polymorphism genotyping were performed on a total of 109 samples of ESCC from 10 patients. This included 42 apparently normal samples of esophageal mucosa at increasing distances from the upper or lower boundaries of the primary tumor to the surgical margins of resection, 43 spatially separated tissue samples within primary tumor and 24 regional lymph node metastases. Phylogenetic analysis was performed to reconstruct ancestor-descendant relationships of clones and the clonal composition of multi-region samples. Mutations of cancer-related genes were validated by deep targeted sequencing (1,168X). Both inter- and intra-tumoral genetic heterogeneity were obvious across multi-region samples among ESCC patients. Clones varying in number from one to seven were discovered within each regional tumor or metastatic sample. Phylogenetic analysis demonstrated complex clonal evolution patterns. Regional lymph node metastases had characteristics of early initiation and polyclonal spreading, and could be derived from carcinoma in situ (CIS) directly. TP53 was the only gene harboring non-silent mutations identified across all multi-region tumor samples of all ten patients. Mutations of TP53 were also found in histologically normal mucosa in sites away from primary tumor.

Effectiveness of Intensive Endoscopic Screening for Esophageal Cancer in China: A Community-Based Study.

Evidence is required to evaluate the effectiveness of population-level endoscopic screening for esophageal cancer (EC). In this study, 5,632 permanent residents aged 25-65 years from 6 villages in Hua County, Henan Province, China, were defined as the screening cohort and were offered intensive endoscopic screening. Residents of all 914 remaining villages in Hua County were included as the control cohort, and age-sex standardization was used to calculate the expected numbers of EC and upper gastrointestinal (GI) tract cancer cases and deaths in the screening cohort. The effectiveness of screening was assessed by comparing observed numbers of cases and deaths with expected numbers after 9-year follow-up of these screened subjects (2007-2016). In the screening cohort, 23 upper GI cancers (including 16 ECs) and 10 upper GI cancer deaths (including 5 EC deaths) were identified, and 47% (standardized incidence ratio = 0.53, 95% confidence interval (CI): 0.33, 0.87) and 66% (standardized mortality ratio = 0.34, 95% CI: 0.14, 0.81) reductions in cumulative EC incidence and mortality were found. For upper GI cancers, incidence and mortality were lowered by 43% (standardized incidence ratio = 0.57, 95% CI: 0.38, 0.86) and 53% (standardized mortality ratio = 0.47, 95% CI: 0.25, 0.88), respectively. This study showed that upper GI tract endoscopy is an effective population-level screening test for EC in high-risk regions.

A Model To Identify Individuals at High Risk for Esophageal Squamous Cell Carcinoma and Precancerous Lesions in Regions of High Prevalence in China.

BACKGROUND & AIMS: We aimed to develop a population-based model to identify individuals at high risk for esophageal squamous cell carcinoma (ESCC) in regions of China with a high prevalence of this cancer. METHODS: We collected findings from 15,073 permanent residents (45-69 years old) of 334 randomly selected villages in Hua County, Henan Province, China who underwent endoscopic screening (with iodine staining) for ESCC from January 2012 through September 2015. The entire esophagus and stomach were examined; biopsies were collected from all focal lesions (or from standard sites in the esophagus if no abnormalities were found) and analyzed histologically. Squamous dysplasia, carcinoma in situ, and ESCC were independently confirmed by 2 pathologists. Before endoscopy, subjects completed a questionnaire on ESCC risk factors. Variables were evaluated with unconditional univariate logistic regression analysis; variables found to be significantly associated with ESCC were then analyzed by multivariate logistic regression modeling. We used the Akaike information criterion to develop our final model structure and the coding form of variables with multiple measures. We developed 2 groups of models, separately defining severe dysplasia and above (SDA) (lesions including severe dysplasia and higher-grade lesions) and moderate dysplasia and above (lesions including moderate dysplasia and higher-grade lesions) as outcome events. Age-stratified and whole-age models were developed; their discriminative ability in the full multivariate model and the simple age model was compared. We performed area under the receiver operating characteristic curve (AUC) and the DeLong test to evaluate model performance. RESULTS: Our age-stratified prediction models identified individuals 60 years of age or younger with SDA with an AUC value of 0.795 (95% confidence interval, 0.736-0.854) and individuals older than 60 years with SDA with an AUC value of 0.681 (95% confidence interval, 0.618-0.743). Factors associated with SDA in individuals 60 years or younger included age closer to 60 years, use of coal or wood as a main source of cooking fuel, body mass index of 22 kg/m2 or less, unexplained epigastric pain, and rapid ingestion of meals. In subjects older than 60 years, SDA associated with age, family history of ESCC, cigarette smoking, body mass index of 22 kg/m2 or less, pesticide exposure, irregular eating habits, intake of high temperature foods, rapid ingestion of meals, and ingestion of leftover food in summer months. Use of our model in screening could have allowed 27% of subjects 60 years or younger and 9% of subjects older than 60 years to avoid endoscopy without missing SDAs. This means that approximately 2500 of endoscopies in total (16.6%) could have been avoided. CONCLUSIONS: We developed a low-cost, easy-to-use model to identify individuals at risk for severe dysplasia or cancer of the esophagus living in a region of China with a high risk of ESCC. This model might be used to select individuals and groups of persons who should undergo endoscopy analysis for esophageal cancer.

Design of an actuator with bionic claw hook-suction cup hybrid structure for soft robot.

To improve the adaptability of soft robots to the environment and achieve reliable attachment on various surfaces such as smooth and rough, this study draws inspiration from the collaborative attachment strategy of insects, cats, and other biological claw hooks and foot pads, and designs an actuator with a bionic claw hook-suction cup hybrid structure. The rigid biomimetic pop-up claw hook linkage mechanism is combined with a flexible suction cup of a 'foot pad' to achieve a synergistic adhesion effect between claw hook locking and suction cup adhesion through the deformation control of a soft pneumatic actuator. A pop-up claw hook linkage mechanism based on the principle of cat claw movement was designed, and the attachment mechanism of the biological claw hooks and footpads was analysed. An artificial muscle-spring-reinforced flexible pneumatic actuator (SRFPA) was developed and a kinematic model of the SRFPA was established and analysed using Abaqus. Finally, a prototype of the hybrid actuator was fabricated. The kinematic and mechanical performances of the SRFPA and entire actuator were characterised, and the attachment performance of the hybrid actuator to smooth and rough surfaces was tested. The results indicate that the proposed biomimetic claw hook-suction cup hybrid structure actuator is effective for various types of surface adhesion, object grasping, and robot walking. This study provides new insights for the design of highly adaptable robots and biomimetic attachment devices.

The positive impact of introducing public engagement as a self-directed learning strategy in undergraduate nervous system education.

Undergraduate medical education in China has shifted from educator-centered learning to self-directed learning (SDL) over the past few decades. Careful design of public engagement activities can enable SDL and empower medical students to pioneer public health and patient safety education. In this study, we aimed to innovate nervous system education by implementing a public engagement model that empowers students to learn about the nervous system by teaching the public. Our goal was to generate greater interest in the nervous system at the undergraduate stage, inspire students' enthusiasm to pursue a career in neurology, and ultimately, contribute to health promotion. During the nervous system module of the second year of the undergraduate curriculum, students were given the option to participate in the public engagement model. Participants were tasked with the creation of educational videos focusing on knowledge, attitudes, and behaviors associated with the prevention and management of neurological diseases and their complications. The videos were made accessible to the general public through the university's official channel at the end of the semester. A total of 117 students (67.24% of all students) chose to participate in the public engagement model. Female students and those with higher Grade Point Averages in the present semester were more likely to participate. The model received strong positive feedback from participants, as students found the public engagement task helpful in learning about the nervous system module as well as in enhancing their public engagement skills. Despite the time and effort consumption, participating in the public engagement task did not affect students' exam scores. The public engagement task is an innovative model in the nervous system curriculum and has the potential to be integrated into a broader range of undergraduate courses. It empowers medical students to pioneer public health and patient safety education.

Risk Factors of Gastrointestinal Perforation with a Poor Prognosis.

Background: Despite medical progress, mortality from gastrointestinal perforation was relatively high. Our study's objective was to identify risk factors associated with a poor prognosis for gastrointestinal perforation. Methods: Patients diagnosed with gastrointestinal perforation at the Longchuan County People's Hospital between January 2019 and February 2022 were the subject of a retrospective analysis of their laboratory data. Patients were grouped based on length of hospital stay, septic shock, and mortality. Results: A total of 240 patients participated in our study. Using univariate and multivariate analysis, we identified several risk factors for gastrointestinal perforation associated with a dismal prognosis. Lower digestive tract perforation (OR=2.418, 95% CI 1.119-5.227, P=0.025), low total protein (OR=0.934, 95% CI 0.879-0.992, P=0.026) and low hemoglobin (OR=0.985, 95% CI 0.971-0.999, P=0.039) were linked to a longer length of stay, especially hemoglobin (OR=0.978, 95% CI 0.966-0.991, P=0.001) in upper digestive tract. High ratio of neutrophils to lymphocytes (NLR) (OR=1.043, 95% CI 1.012-1.076, P=0.007), high lymphocyte-to-monocyte ratio (LMR) (OR=2.158, 95% CI 1.495-3.115, P<0.001) and low prognostic nutrition index (PNI) (OR=0.814, 95% CI 0.751-0.833, P<0.001) predicted septic shock. In upper digestive tract, PLR (OR=1.001, 95% CI 1.000-1.002, P=0.067), LMR (OR=2.160, 95% CI 1.440-3.240, P<0.001) and PNI (OR=0.843, 95% CI 0.767-0.926, P<0.001) were risk factors for septic shock, and total protein (OR=0.796, 95% CI 0.686-0.923, P=0.003) was a risk factor for septic shock in lower digestive tract. High NLR (OR=1.056, 95% CI 1.019-1.093, P=0.003), high LMR (OR=1.760, 95% CI 1.177-2.632, P=0.006) and low PNI (OR=0.832, 95% CI 0.754-0.918, P<0.001) were the risk factors of mortality. In subgroup analysis of perforation site, albumin (OR=0.820, 95% CI 0.719-0.934, P=0.003) and LMR (OR=1.506, 95% CI 1.069-2.123, P=0.019) were risk factors for mortality in upper digestive tract and PNI (OR=0.636, 95% CI 0.445-0.908, P=0.013) was a risk factor for mortality in lower digestive tract. Conclusion: Our research found that the perforation site, total protein, albumin, hemoglobin, NLR, LMR, PLR and PNI were risk factors for gastrointestinal perforation with a poor prognosis.

Absence of Lugol staining indicates initiation of esophageal squamous cell carcinoma: A combined genomic and epidemiologic study.

The genomic characteristics during the carcinogenic process of esophageal squamous cell carcinoma (ESCC) remain largely unknown. We report here the genomic characteristics of 106 esophageal tissues of various stages from a population-based screening cohort in China ("Endoscopic Screening for Esophageal Cancer in China" trial) and 57 ESCC tissues from a local hospital. A significant increase in somatic mutation and copy number alterations is observed in the non-dysplastic Lugol unstaining lesions (ND-LULs). Extensive clonal expansion has emerged in the ND-LULs to an extent similar to that in higher-stage lesions. The burden of genomic alterations correlates with the size of LULs in the ND-LULs. 8-year follow-up shows that ND-LULs harbor an increased risk of progression to ESCC (adjusted IRR6-10 mm vs. none = 4.66, adjusted IRR>10 mm vs. none = 40.70), and the risk is correlated with LUL size for both non-dysplastic and dysplastic lesions. Lugol unstaining can be the initial stage in the carcinogenic process of ESCC.

Application and Research Progress of High Frequency Ultrasound in the Diagnosis of Chronic Inflammatory Neuropathies.

In recent years, clinicians have gradually improved their understanding of multiple neuropathy and have done some studies about chronic inflammatory neuropathies, for example, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and Lewis-Sumne syndrome. The early diagnosis is very important for the next step treatment and long-term prognosis. At present, the disease mainly depends on clinical and neural electrophysiological examination, but imaging studies are few. In recent years, with the rapid development of high frequency ultrasound, it could clearly show the morphology of the nerve, and it has been an emerging diagnosis tool of polyneuropathies. This article mainly reviews the application and the latest research progress of high frequency ultrasound in these diseases.

What factors affect the quality of medical students' doctoral theses? A comparative study in affiliated hospitals of a Chinese university.

Background: The quality of doctoral theses decides whether medical PhD and MD candidates could get their doctoral degree successfully. Good quality theses could be rewarded by Peking University which is a great honor for both doctoral candidates and for mentors. The present study aims to determine factors affecting the quality of medical doctoral theses. Methods: Honored theses and nonhonored theses were matched 1:3 randomly by specialty and submission year. Conditional logistic regressions were utilized. Results: Five domains comprising 17 indicators were put forward to evaluate the quality of doctoral theses. 41 honored theses and 119 matched nonhonored theses from years 2012-2016 were analyzed by univariate and multivariate conditional logistic regression. Degree type (OR: 107.56, 95%CI: 1.20-9632.70, P=0.041), first author impact factor (OR:1.24, 95%CI: 1.01-1.53, P=0.040) and correctly reported statistic results (OR: 43.18, 95%CI: 1.88-991.61, P=0.019) are independent factors influencing the quality of a doctoral thesis. Conclusions: The present study indicates that there is a significant gap between PhD and MD students on quality of thesis. The rewarded theses have a feature of high first author impact factor. However, most medical students need more training on statistics to improve the quality of their doctoral theses.

Mutation landscape and intra-tumor heterogeneity of two MANECs of the esophagus revealed by multi-region sequencing.

Mixed adenoneuroendocrine carcinoma (MANEC) in the esophagus is an infrequent but highly malignant cancer with few known genomic alterations. We conducted whole-exome sequencing and whole-genome SNP genotyping for 4-6 tumor subregions and 5-6 adjacent normal tissue sites and 1-3 lymph node metastases in two esophageal MANECs to detect somatic mutations and copy number alterations, and to explore their spatial heterogeneity and underlying clonal structure. TP53 mutation, RB1 deletion or LOH, and PIK3CA, PTEN, KRAS, SOX2, DVL3, TP63 amplification appeared in all regions in both tumors. Mutations falling in known cancer genes tended to show higher variant allele frequencies than those not falling in these genes in at least one of the cases. Phylogenetic analyses of the samples and underlying subclones suggested extensive migration across different tumor regions and from some regions to the lymph nodes. Lymph node metastases appeared to have been seeded by both early founder cells as well as subsequent, locally emerging daughter clones. A phenotypically normal tissue site carried most of the mutations found in neighboring tumor samples, implying field cancerization. Understanding such complex genetic heterogeneity within each patient will be important for guiding clinical decisions.

Prevalence and genotype distribution of human papillomavirus among Hakka women in China.

BACKGROUND: Human papillomavirus (HPV) infection is the primary risk factor for cervical cancer. HPV genotypes are associated with varying degrees of pathogenicity. To better formulate strategies for cervical cancer prevention, we investigated the population-specific distribution of HPV genotypes, including those with high carcinogenicity. METHODS: From January to December 2012, a cervical cancer-screening program for HPV infection in Hakka women of Heyuan City Guangdong province was conducted. Of 736,000 women residents, 8,284 volunteers were recruited. The cytology specimens of 107 women were not adequate and excluded. Thus, 8,177 women submitted to polymerase chain reaction (PCR) sequencing of 16 HPV genotypes via MassARRAY spectrometry. RESULTS: Risk stratification based on genotypes indicated that the prevalence of overall, high-risk, and low-risk HPV infections was 12.27%, 14.20%, and 0.79%, respectively. Of the 1,003 women positively infected, 82.75% were infected with a single HPV type; 17.25% were infected with ≥2 types. Analysis revealed a U-shaped curve in HPV prevalence that correlated with age group, with peaks at ages 18-24 y (22.03%) and 60-65 y (25%). The most frequently detected HPV genotype was HPV-52 (26.81%), and then HPV-16 (17.54%), HPV-58 (14.25%), HPV-18 (10.16%), HPV-68 (8.27%), HPV-39 (5.68%), and HPV-51 (5.38%). CONCLUSIONS: HPV-52 is the most prevalent genotype infecting Hakka women. Therefore, vaccination against HPV-52 is imperative. The prevalence of HPV infection is highest in the younger (18-24 y) and older (60-65 y) age groups, indicating that screening for HPV in Hakka women should be performed early and maintained in the elderly.