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The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Although multiple common susceptibility loci for lung cancer (LC) have been identified by genome-wide association studies, they can explain only a small portion of heritability. The etiological contribution of rare deleterious variants (RDVs) to LC risk is not fully characterized and may account for part of the missing heritability. Here, we sequenced the whole exomes of 2777 participants from the Environment and Genetics in Lung cancer Etiology study, a homogenous population including 1461 LC cases and 1316 controls. In single-variant analyses, we identified a new RDV, rs77187983 [EHBP1, odds ratio (OR) = 3.13, 95% confidence interval (CI) = 1.34–7.30, P = 0.008] and replicated two previously reported RDVs, rs11571833 (BRCA2, OR = 2.18; 95% CI = 1.25–3.81, P = 0.006) and rs752672077 (MPZL2, OR = 3.70, 95% CI = 1.04–13.15, P = 0.044). In gene-based analyses, we confirmed BRCA2 (P = 0.007) and ATM (P = 0.014) associations with LC risk and identified TRIB3 (P = 0.009), involved in maintaining genome stability and DNA repair, as a new candidate susceptibility gene. Furthermore, cases were enriched with RDVs in homologous recombination repair [carrier frequency (CF) = 22.9% versus 19.5%, P = 0.017] and Fanconi anemia (CF = 12.5% versus 10.2%, P = 0.036) pathways. Our results were not significant after multiple testing corrections but were enriched in cases versus controls from large scale public biobank resources, including The Cancer Genome Atlas, FinnGen and UK Biobank. Our study identifies novel candidate genes and highlights the importance of RDVs in DNA repair-related genes for LC susceptibility. These findings improve our understanding of LC heritability and may contribute to the development of risk stratification and prevention strategies.

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Periodontal disease may be associated with increased breast cancer risk, but studies have not considered invasive breast cancer and ductal carcinoma in situ (DCIS) separately in the same population. We assessed the relationship between periodontal disease and breast cancer in a large prospective cohort study. The Sister Study followed women without prior breast cancer ages 35 to 74 years from 2003 to 2017 (N = 49,968). Baseline periodontal disease was self-reported, and incident breast cancer was ascertained over a mean follow-up of 9.3 years. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression, adjusting for multiple potential confounders, including smoking status. Heterogeneity in risk for invasive breast cancer versus DCIS was also estimated. About 22% of participants reported a history of periodontal disease at baseline. A total of 3,339 incident breast cancers (2,607 invasive breast cancer, 732 DCIS) were identified. There was no clear association between periodontal disease and overall breast cancer risk (HR = 1.02; 95% CI, 0.94–1.11). However, we observed a nonstatistically significant suggestive increased risk of invasive breast cancer (HR = 1.07; 95% CI, 0.97–1.17) and decreased risk of DCIS (HR = 0.86; 95% CI, 0.72–1.04) associated with periodontal disease, with evidence for heterogeneity in the risk associations (relative HR for invasive breast cancer versus DCIS = 1.24; 95% CI, 1.01–1.52). A case-only analysis for etiologic heterogeneity confirmed this difference. We observed no clear association between periodontal disease and overall breast cancer risk. The heterogeneity in risk associations for invasive breast cancer versus DCIS warrants further exploration.

AIM: Studies have found that periodontal disease and tooth loss are associated with increased mortality; however, associations with cause-specific mortality and all-cause mortality within specific subgroups have not been thoroughly investigated. MATERIALS AND METHODS: We examined the association of self-reported periodontal disease and disease/decay-related tooth loss with subsequent all-cause and cause-specific mortality in the Sister Study, a prospective cohort study of 50 884 women aged 35 to 74 years at baseline whose sister was diagnosed with breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for relevant confounders. RESULTS: With a mean follow-up of 10.9 years (range 0.1–14.3), 2058 women died. Participants with periodontal disease had a slightly higher rate of all-cause mortality (HR=1.08, 95% CI 0.98–1.19), while participants with tooth loss had an increased rate of all-cause mortality (HR=1.15, 95% CI 1.05–1.26). For cause-specific mortality, women with tooth loss had increased rates of death from circulatory system diseases, respiratory system diseases, and endocrine/metabolic diseases. Results varied in stratified models, but no heterogeneity across strata was found. CONCLUSION: In this large prospective study, periodontal disease and tooth loss were associated with all-cause and certain specific cause-specific mortality outcomes.

Background Current methods for cervical cancer screening result in an increased number of referrals and unnecessary diagnostic procedures. This study aimed to develop and evaluate a more accurate model for cervical cancer screening. Methods Multiple predictors including age, cytology, high-risk human papillomavirus (hrHPV) DNA/mRNA, E6 oncoprotein, HPV genotyping, and p16/Ki-67 were used for model construction in a cross-sectional population including women with normal cervix (N = 1085), cervical intraepithelial neoplasia (CIN, N = 279), and cervical cancer (N = 551) to predict CIN2+ or CIN3+. A base model using age, cytology, and hrHPV was calculated, and extended versions with additional biomarkers were considered. External validations in two screening cohorts with 3-year follow-up were further conducted (NCohort-I = 3179, NCohort-II = 3082). Results The base model increased the area under the curve (AUC, 0.91, 95% confidence interval [CI] = 0.88–0.93) and reduced colposcopy referral rates (42.76%, 95% CI = 38.67–46.92) compared to hrHPV and cytology co-testing in the cross-sectional population (AUC 0.80, 95% CI = 0.79–0.82, referrals rates 61.62, 95% CI = 59.4–63.8) to predict CIN2+. The AUC further improved when HPV genotyping and/or E6 oncoprotein were included in the base model. External validation in two screening cohorts further demonstrated that our models had better clinical performances than routine screening methods, yielded AUCs of 0.92 (95% CI = 0.91–0.93) and 0.94 (95% CI = 0.91–0.97) to predict CIN2+ and referrals rates of 17.55% (95% CI = 16.24–18.92) and 7.40% (95% CI = 6.50–8.38) in screening cohort I and II, respectively. Similar results were observed for CIN3+ prediction. Conclusions Compared to routine screening methods, our model using current cervical screening indicators can improve the clinical performance and reduce referral rates.

This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer (HNC).56 incident HNC cases were identified, and 112 controls were incidence-density matched to cases. DNA extracted from pre-diagnostic oral wash samples was whole-genome shotgun metagenomic sequenced to measure the overall oral microbiome. ITS2 gene qPCR was used to measure the presence of fungi. ITS2 gene sequencing was performed on ITS2 gene qPCR positive samples. We computed taxonomic and functional alpha-diversity and beta-diversity metrics. The presence and relative abundance of groups of red-complex (e.g., Porphyromonas gingivalis) and/or orange-complex (e.g., Fusobacterium nucleatum) periodontal pathogens were compared between cases and controls using conditional logistic regression models and MiRKAT.Participants with higher taxonomic microbial alpha-diversity had a non-statistically significant decreased risk of HNC. No case-control differences were found for beta diversity by MiRKAT model (all p 0.05). A greater relative abundance of red-complex periodontal pathogens (OR = 0.51, 95 % CI = 0.26-1.00), orange-complex (OR = 0.38, 95 % CI = 0.18-0.83), and both complexes' pathogens (OR = 0.32, 95 % CI = 0.14-0.75), were associated with reduced risk of HNC. The presence of oral fungi was also strongly associated with reduced risk of HNC compared with controls (OR = 0.39, 95 % CI = 0.17-0.92).Greater taxonomic alpha-diversity, the presence of oral fungi, and the presence or relative abundance of multiple microbial species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of HNC. Future studies with larger sample sizes are needed to evaluate these associations.

Periodontal disease may be associated with increased breast cancer risk, but studies have not considered invasive breast cancer and ductal carcinoma in situ (DCIS) separately in the same population. We assessed the relationship between periodontal disease and breast cancer in a large prospective cohort study. The Sister Study followed women without prior breast cancer ages 35 to 74 years from 2003 to 2017 (N = 49,968). Baseline periodontal disease was self-reported, and incident breast cancer was ascertained over a mean follow-up of 9.3 years. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression, adjusting for multiple potential confounders, including smoking status. Heterogeneity in risk for invasive breast cancer versus DCIS was also estimated. About 22% of participants reported a history of periodontal disease at baseline. A total of 3,339 incident breast cancers (2,607 invasive breast cancer, 732 DCIS) were identified. There was no clear association between periodontal disease and overall breast cancer risk (HR = 1.02; 95% CI, 0.94–1.11). However, we observed a nonstatistically significant suggestive increased risk of invasive breast cancer (HR = 1.07; 95% CI, 0.97–1.17) and decreased risk of DCIS (HR = 0.86; 95% CI, 0.72–1.04) associated with periodontal disease, with evidence for heterogeneity in the risk associations (relative HR for invasive breast cancer versus DCIS = 1.24; 95% CI, 1.01–1.52). A case-only analysis for etiologic heterogeneity confirmed this difference. We observed no clear association between periodontal disease and overall breast cancer risk. The heterogeneity in risk associations for invasive breast cancer versus DCIS warrants further exploration.

The Roche Cobas (Cobas) and BD Onclarity (Onclarity) human papillomavirus (HPV) assays are convenient, PCR-based, HPV DNA tests; currently, data on performance of Onclarity in Chinese women is limited. We aimed to evaluate the clinical performance of Onclarity for detecting cervical lesions in Chinese women.In total, 1122 women were enrolled into this study. Exfoliated cervical cells were collected in PreservCyt medium and were tested using Cobas and Onclarity. Cytology and histology were interpreted by senior cytologists and a panel of pathologists, respectively, at Cancer Hospital, Chinese Academy of Medical Sciences.The assays showed excellent concordance for HPV16 (kappa = 0.91, 95% CI: 0.85-0.97) and for 12 other high-risk types (HPV31/33/35/39/45/51/52/56/58/59/66/68, kappa = 0.84, 95% CI: 0.78-0.90), and very good concordance for HPV18 (kappa = 0.75, 95% CI: 0.69-0.81). No difference for ≥CIN2 sensitivity was observed between Onclarity and Cobas (both 90.5%); and theCIN2 specificity for detection was similar between Onclarity (84.2%, 95% CI: 81.6-86.4) and Cobas (80.4%, 95% CI: 77.6-82.8). When combined with cytology triage, the colposcopy referral rate point estimate was slightly lower for Onclarity (9.0%) than for Cobas (11.0%), with the same ≥CIN2 sensitivity of 75.0% (95% CI: 53.1-88.8) for Onclarity and Cobas.Onclarity exhibited comparable screening performance and triage efficiency compared to Cobas in detection of cervical lesions in Chinese women.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic, and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and non-malignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N=379 breast cancer cases, N=102 non-malignant breast disease cases, N=414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith’s phylogenetic diversity), beta diversity (Bray Curtis and unweighted/weighted UniFrac distance), and presence and relative abundance of select taxa with breast cancer and non-malignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest vs. lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend

Factors that differentiate risk of cervical cancer associated with infection with single versus multiple HPV types are yet undefined. We hypothesize that E6 oncoprotein is one determining factor. This cross-sectional, multicenter study was performed between 2013 and 2017. A total of 1,781 women were recruited from six hospitals. Samples were tested for presence of 14 types of high-risk HPV DNA. HPV16/18-positive samples were also tested for HPV16/18-E6 oncoprotein. Of 1,781 subjects, 687 (38.6%) tested positive for HPV16/18. HPV16/18 single infections were associated with higher E6 positivity rates compared with multiple infections only for cancer cases (HPV16: 92.2% vs. 76.5%; HPV18: 93.9% vs. 62.1%) but not for normal histopathology or cervical intraepithelial neoplasia. In HPV16/18 coinfection subjects, the positivity rate was 42.9% for HPV16-E6 and 42.9% for HPV18-E6. The combined positivity rate of either HPV16-E6 or HPV18-E6 among HPV16/18 coinfection subjects was 78.6%, similar with HPV16 (74.8%) and HPV18 (79.5%) single-infection subjects. The positivity rates of HPV16/18 E6 oncoprotein varied depending on the HPV-type composition in multiple infection (“clusters”) including HPV types other than 16 and 18. Multiple infection clusters most likely to express HPV16-E6 and HPV18-E6 were HPV16/52 (61.5%) and HPV18/52 (66.7%), and the less were HPV16/45 (10.0%) and HPV18/51 (16.7%), respectively. Patterns of E6 oncoprotein expression varied depending on clustering types. However, expression was greatest in women with single HPV-type infections compared with those with multiple HPV types regardless of histopathology. Our findings provided new insight of natural history of cervical cancer.

Objective: This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer. Methods: Among 34,262 participants with oral wash samples, 60 incident head and neck cancer cases were identified during a mean of 6.25±1.28 years of follow-up. Two controls were matched to each case by age at sample collection, sex, and baseline smoking history, and available controls were not diagnosed with head and neck cancer over follow-up. Whole genome shotgun metagenomic sequencing was used to measure the overall oral microbiome, and ITS2 gene qPCR was used to measure the presence of fungi in pre-diagnostic oral wash samples. ITS2 gene sequencing was performed on ITS2 qPCR positive samples. Taxonomic and functional alpha-diversity and beta-diversity metrics were computed. Presence/absence and relative abundance of groups of red- and/or orange-complex periodontal pathogens were also calculated. Conditional logistic regression models and MiRKAT were used to investigate the case-control associations. Results: Participants with higher taxonomic microbial alpha-diversity had a decreased risk of head and neck cancer with odds ratios per every 10 observed species of 0.87 (95% CI=0.75-1.004, P=0.057), and per one unit of Faith’s PD and the Shannon index of 0.84 (95% CI=0.72-0.99, P=0.032) and 0.52 (95% CI=0.29-0.94, P=0.032), respectively. No case-control differences were found for beta diversity (all p>0.05). The presence of red-complex periodontal pathogens was non-significantly associated with reduced risk of head and neck cancer (OR=0.41, 95% CI=0.17-1.01, P=0.052). Greater relative abundance of red-complex (OR=0.29, 95% CI=0.09-0.94, P=0.040), orange-complex (OR=0.45, 95% CI=0.22-0.89, P=0.022), and both complexes combined (OR=0.46, 95% CI=0.25-0.82, P=0.009), were associated with reduced risk of head and neck cancer. The presence of oral fungi was also strongly associated with reduced risk of head and neck cancer compared with controls (OR=0.39, 95% CI=0.17-0.87, P=0.022). Conclusions: Greater taxonomic alpha-diversity and the presence or relative abundance of multiple bacterial or fungal species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of head and neck cancer. Citation Format: Zeni Wu, Yongli Han, Yunhu Wan, Xing Hua, Casey L. Dagnall, Kristine Jones, Amy Hutchinson, Belynda D. Hicks, Weiyin Zhou, Linda Liao, Heather Hallen-Adams, Jianxin Shi, Christian C. Abnet, Rashmi Sinha, Anil Chaturvedi, Emily Vogtmann. The oral microbiome and the risk of head and neck cancer: A nested case-control study in the NIH-AARP [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 687.

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% (95%CI: 87.9, 92.9) 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 (95.7% [95%CI: 92.0-97.7], 96.3% [95%CI: 92.1-98.3]), 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 (71.0% [95%CI: 65.9-75.7], 62.8% [95%CI: 57.8-67.5]), 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.

HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.

Objectives. To estimate the unintentional poisoning burden and risk factors in China from 1990 to 2015. Methods. We extracted data from the Global Burden of Disease Study 2015 to compare mortality, prevalence, disability-adjusted life years (DALYs), years of life lost, years lived with a disability, and risk factors of unintentional poisoning in China. We determined the median of the percent change and 95% uncertainty interval for the period between 1990 and 2015. Results. The age-standardized unintentional poisoning death rate decreased by 61.8% from 1990 (4.1 per 100 000) to 2015 (1.6 per 100 000). The age-standardized prevalence decreased from 1990 (87.9 per 100 000) to 2010 (39.0 per 100 000), but rebounded in 2015 (42.6 per 100 000). All risk factors combined accounted for 14.9% of unintentional poisoning DALYs in 2015. The leading risk factors for unintentional poisoning DALYs were alcohol and drug use and occupational risks. Conclusions. China has made substantial progress in reducing the mortality attributable to unintentional poisoning, but the prevalence and absolute number of patients has been increasing again since 2010. The growing contribution from alcohol and drug use requires increased attention.

// Hai-Rui Wang 1, 2, * , Yu-Cong Li 3, * , Hui-Qin Guo 4 , Lu-Lu Yu 1 , Zeni Wu 1 , Jian Yin 1 , Guang-Dong Liao 5 , Yi-Min Qu 2 , Yu Jiang 2 , Dong Wang 3 and Wen Chen 1 1 Department of Cancer Epidemiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 2 School of Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 3 Department of Gynecological Oncology, Chongqing Cancer Institute & Hospital & Cancer Center, Chongqing, PR China 4 Department of Pathology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 5 Department of Gynecology and Obstetrics, The West China Second University Hospital, Sichuan University, Chengdu, PR China * These authors have contributed equally to this work Correspondence to: Wen Chen, email: chenwen@cicams.ac.cn Dong Wang, email: cqwindow120@163.com Keywords: HPV, p16/Ki-67 dual staining, p16/mcm2, cervical cancer screening, cytology Received: October 15, 2016 Accepted: July 11, 2017 Published: August 03, 2017 ABSTRACT Most human papillomavirus (HPV) infections are transient and additional triage approaches should be built after HPV-based primary cervical cancer screening. We evaluated the accuracy of p16/Ki-67 and p16/mcm2 dual staining as biomarkers for triaging HPV positive women in China. 4070 participants aged 35 to 64 years attending ongoing cervical cancer screening were enrolled in 2015-2016. Cervical exfoliated cells were collected for HPV DNA analysis and the residual positive specimens were tested for liquid-based cytology and biomarkers. Women infected with HPV 16/18 type or other 12 high-risk HPV types with abnormal cytology results received colposcopy. We found the positive rates of both biomarkers increased significantly with histology severity. p16/Ki-67 positivity in HPV16/18 group, other 12 high-risk HPV group and HPV negative group was 50.0%, 33.7% and 8.9%, respectively. The corresponding p16/mcm2 positivity was 70.0%, 56.3% and 6.7%, respectively. The sensitivity and specificity of p16/Ki-67 for CIN2+ in all HPV-positive women were 91.7% and 63.5%, with a referral rate of 36.2%, while p16/mcm2 were 87.5% and 42.1%, with a referral rate of 58.4%, respectively. The sensitivity of p16/Ki-67 increased to 95.8% for CIN2+ and 100% for CIN3+ when combined with high-grade cytology, without decrease in specificity. Our studies suggest that p16/Ki-67 is an efficient triaging biomarker for HPV-positive women and could reduce colposcopy workload. p16/mcm2 is more sensitive compared with cytology for identifying cervical lesions.

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (Ptrend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (Ptrend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8–42.4) and OR for dual stain− (ORDS−) of 3.87(1.89–7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05–21.0) and ORDS− of 1.27(0.38–4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.

Coinfections with multiple types of human papillomavirus (HPV) occur in cervical adenocarcinoma (ADC). However, it remains unclear the clustering patterns of multiple types in HPV coinfections and relevant factors in ADC. A total of 718 paraffin-embedded ADC specimens were collected in China and tested for HPV genotypes using SPF10-INNO-LIPA. The prevalence of HPV coinfections and clustering patterns by geographical regions, histological subtypes and ages were assessed. Type-specific attribution of HPV to ADC adjusted by HPV coinfections were calculated. The prevalence of HPV coinfections was found to be 8.4% in ADC cases with slight variation by geographic regions between 2.2% and 12.5%. The 88.3% of all HPV multiple infections in ADC were two types of HPV coinfections with predominant combination of HPV 16 and HPV 18. The attribution to ADC was 88.0% for HPV 16/18 targeted by bivalent and quadrivalent vaccine and 96.8% for HPV 16/18/31/33/45/52/58 targeted by nonavalent vaccine. Clustering patterns of multiple types were related with histological categories and age at diagnosis. In conclusion, HPV coinfections are uncommonly prevalent in ADC cases with slight variation by geographic regions and distinct clustering patterns of multiple types by histological subtypes and ages at diagnosis. The high attribution of carcinogenic HPV types to ADC predicts potential protection of HPV vaccine against ADC.

The relationship between HPV viral load and histological grades in the development of cervical cancer is in argument. It is helpful to better understand the association by quantitatively detecting viral load of HPV16, 18, and a pool of 12 other high-risk HPV type (OT) independently on the samples of precancer and cancer. A cross-sectional study was performed in five medical centers of China. Histological diagnosis made by local pathologists was adjudicated via a pathology expert panel. A fully automated real-time PCR test was used for the measurement of HPV16, 18, OT, and human β-globin gene. A total of 2,513 women [1,341 normal, 209 low grade intraepithelial lesion (LSIL), 392 high grade intraepithelial lesion (HSIL), 520 squamous cell carcinoma (SCC), and 51 adenocarcinoma (ADC)] were included. There is a linear increase in the total 14 HPV viral load with histological grade from normal to SCC. This trend was not observed in HPV18 infection but HPV16. The viral load for OT was low in normal, peaked in LSIL and HSIL, and declined in SCC and ADC. In the co-infection of HPV16 and HPV18, HPV16 viral load was significantly higher than HPV18 in LSIL and HSIL. In co-infection of HPV16 and OT, higher HPV16 viral load was also seen in SCC and ADC. Viral load of HPV16 increases with cervical lesion grade and is predominant in cervical cancer. HPV18 viral load is low in precancer, but going up in cancer. OT viral load shows inverse trend of HPV18. J. Med. Virol. 89:535-541, 2017. © 2016 Wiley Periodicals, Inc.

// Lu-Lu Yu 1 , Hui-Qin Guo 2 , Xiao-Qin Lei 1 , Yu Qin 1 , Ze-Ni Wu 1 , Le-Ni Kang 3 , Xun Zhang 2 , You-Lin Qiao 1 and Wen Chen 1 1 Department of Cancer Epidemiology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 2 Department of Pathology, National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China 3 National Office for Maternal and Child Health Surveillance of China, West China Second University Hospital, Sichuan University, Chengdu, PR China Correspondence to: Wen Chen, email: // Keywords : HPV persistent infection; p16/Ki-67 co-expression; cervical cancer screening Received : April 24, 2016 Accepted : August 23, 2016 Published : August 30, 2016 Abstract Purpose: To evaluate the association of p16/Ki-67 co-expression and persistence of high-risk human papillomavirus (HR-HPV) infection as well as cervical abnormalities. Methods: We performed a 3-year cohort study among which 2498 Chinese women aged 25 to 65 years were screened by different HPV tests in 2011. 690 women who were positive at any of the tests and a random sample of 164 women with all negative results received colposcopy, cervical specimens for cobas HPV test (Roche diagnostics) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas, Liquid-based cytology, HPV E6 test (Arbor Vita Corporation) and p16/Ki-67 dual staining (Roche diagnostics) in 2014. Colposcopy and biopsies was performed on women with any abnormal result. Results: Compared to women without HR-HPV persistent infection, women in the HR-HPV persistence group had a higher risk of p16/Ki-67 positive, with an adjusted Odds Ratio(OR) and 95% confidence interval (CI) of 6.29 (4.07-9.72); moreover, adjusted odds ratio for women who had HPV16/18 persistent infection was nearly 4-folder higher than women with other 12 HR-HPV persistent infection (adjusted OR = 17.15, 95% CI: 7.11-41.33 vs adjusted OR = 4.68, 95% CI: 2.89-7.58). Additionally, p16/Ki-67 positivity rate significantly increased with the severity of the cytological and histological abnormalities, and resulted strongly associated with a CIN2+ diagnosis (OR = 16.03, 95% CI: 4.46-57.59). Conclusions: p16/Ki-67 co-expressions associated strongly with HR-HPV persistence, especially with HPV16/18, and the presence of a CIN2+ lesion. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

Background and objective: Breast cancer burden is rising in Africa; however, breast cancer risk factors remain largely understudied in this population. The gut microbiome may play a role in the etiology of breast cancer through the regulation of estrogen homeostasis and other metabolic or immunologic pathways. We investigated the association of fecal bacteria with breast neoplasms in a case-control study conducted in Accra and Kumasi, Ghana, comprising 102 non-malignant breast disease cases, 379 invasive breast cancer cases, and 414 population-based controls nested within the Ghana Breast Health Study. Methods: We used the MO-BIO PowerMag kit for DNA extraction and sequenced the V4 region of 16S rRNA gene to characterize bacteria in fecal samples. We used DADA2 to process sequencing data. We calculated estimates of alpha diversity (observed sequence variants, Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray Curtis and unweighted/weighted UniFrac), and presence/absence and relative abundance of select taxa. We then estimated the associations of the microbial metrics with non-malignant breast disease and malignant breast cancer using multivariable unconditional logistic regression. Results: Odds of malignant breast cancer were statistically significantly lower with increasing alpha diversity (all Ptrends 0.1) but was statistically significantly different for both case groups compared controls (all p's Conclusions: Our findings suggest lower fecal alpha diversity, differences in overall microbial composition, and prevalence of certain taxa involved in estrogen metabolism may be associated with both non-malignant breast disease and invasive breast cancer. Given that the gut bacteria are potentially modifiable and targetable, our findings warrant further investigation into the role of the gut microbiota in hormone regulation and etiology of breast cancer in integrative, prospective studies. Citation Format: Doratha Byrd, Emily Vogtmann, Zeni Wu, Autumn Hullings, Xing Hua, Thomas Ahearn, James J. Goedert, Jianxin Shi, Jonine Figueroa, Louise Brinton, Montserrat Garcia-Closas, Rashmi Sinha. Associations of fecal microbial profiles with non-malignant breast disease and breast cancer in the Ghana Breast Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4638.

Background This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining in the detection of cervical intraepithelial neoplasia grade 2 or 3 or worse (CIN2+/CIN3+) in Chinese women. Methods Cervical exfoliated cells were collected from 537 eligible women and were used for liquid-based cytology (LBC), p16/Ki-67 dual staining, and human papillomavirus (HPV) DNA testing. All women received colposcopy with biopsies taken at abnormal sites. Histopathological diagnoses were used as the gold standard. Results p16/Ki-67 staining had a positivity rate of 43.58% overall; the rate increased significantly with histological severity (p0.001). The sensitivities of p16/ki-67 for detecting CIN2+ and CIN3+ were 88.10% and 91.30%, respectively. Compared with high-risk HPV (HR-HPV), sensitivity of p16/Ki-67 was lower for detecting CIN2+ (88.10% versus 95.71%), but similar for detecting CIN3+ (91.30% versus 96.27%). Specificities of p16/Ki-67 were 85.02% for detecting CIN2+ and 76.86% for detecting CIN3+, values similar to those for LBC (84.71% for CIN2+, 80.05% for CIN3+) but higher than those for HR-HPV (62.77% for CIN2+, 71.25% for CIN3+). All the tests performed better in women30 years. With respect to the performance of triage for women with ASC-US, sensitivities of p16/Ki-67 were 86.36% for detecting CIN2+ and 83.33% for detecting CIN3+, values similar to those of HR-HPV. However, specificities of p16/Ki-67 were both higher than those of HR-HPV (85.96% versus 67.54% for CIN2+, 79.84% versus 62.90% for CIN3+). Conclusion P16/Ki-67 dual staining could probably provide an optional method for China's national cervical cancer screening, and could also be considered as an efficient method of triage for managing women with ASC-US.

A hospital-based multicenter, retrospective study was conducted to compare the distribution of human papillomavirus (HPV) in squamous cell carcinoma (SCC) and cervical adenocarcinoma (CADC) in China.Paraffin-embedded tissue blocks diagnosed as SCC and CADC across China were collected, as well as the total number of diagnosed invasive cervical cancer of the 9 selected centers. DNA enzyme immunoassay, reverse hybridization, and multiplex type-specific polymerase chain reaction were used for HPV genotyping.The ratios of CADC to SCC were increasing from 2005 to 2010, in parallel with HPV prevalence in CADC. In 630 patients with SCC (mean ± SD age, 45.40 ± 10.30) and 718 patients with CADC (mean ± SD age, 46.09 ± 10.59) recruited, HPV prevalence rates were 97.6% and 74.5%, respectively. Human papillomavirus viral load for SCC is significantly higher than that for CADC. Most common HPV types distributed in SCC and CADC were HPV-16 (78.5%, 75.1%-81.6%; 47.1%, 42.9%-51.3%), HPV-18 (8.0%, 6.1%-10.4%; 41.1%, 37.0%-45.3%), HPV-52 (2.3%, 1.4%-3.8%; 5.6%, 4.0%-7.9%), and HPV-45 (1.1%, 0.6%-2.3%; 3.9%, 2.6%-5.9%). Different diagnostic mean ± SD age for HPV-16/HPV-18 versus other high-risk HPV types were observed: SCC (44.5 ± 9.94 vs 51.0 ± 10.83, p.05) and CADC (44.1 ± 9.44 vs 47.4 ± 10.41, p = .006). For HPV-negative cases, mean ± SD age was 46.1 ± 10.73 in SCC and 50.3 ± 11.85 in CADC, which were older than the positive (45.4 ± 10.31, 44.5 ± 9.64). HPV-16 and HPV-18 were the most frequent HPV types in both histological types, and HPV-18 was more frequent in CADC than in SCC.Human papillomavirus infection was identified more often in SCC than in CADC. Women with HPV-associated cancers, especially HPV-16/HPV-18, were of a younger age at diagnosis when compared with non-HPV-associated cancers.

Background It has been reported that high HPV DNA load and elevated E6 protein expression correlate with cervical cancer, but no epidemiological study has been performed. Objectives To assess the association between type-specific HPV DNA load and presence of E6 protein in cervical intraepithelial neoplasia and cancer. Study design This study was a cross-sectional multicenter study performed between 2013 and 2017. A total of 1717 women (normal histopathology: n = 916; CIN1: n = 94; CIN2: n = 63; CIN3: n = 130; SCC: n = 474; adenocarcinoma: n = 40) were included. HPV DNA load and presence of E6 protein were detected. DNA load was measured as log copies/10,000 cells. Results The HPV16/18-E6 positivity rates increased from negative for DNA to the highest load grade. Compared to the HPV16 DNA negatives, women with low (RR = 31.5, 95%CI = 18.9–52.5), medium-low (RR = 133.5, 95%CI = 77.3–230.7), medium-high (RR = 247.9, 95%CI = 134.9–455.6) and high DNA loads (RR = 677.9, 95%CI = 301.6–1523.7) had increasingly higher relative ratios of HPV16-E6 expression. The association of HPV18-E6 with its DNA load was also significant for low (RR = 27.9, 95%CI = 10.4–74.9), medium-low (RR = 89.0, 95%CI = 32.8–241.3), medium-high (RR = 276.8, 95%CI = 76.7–998.9) and high grade (RR = 441.2, 95%CI = 97.7–1992.4). The positivity rates of both HPV16 DNA and E6 protein increased consistently with the severity of diseases from normal histopathology to SCC. Unlike HPV16, the trends of HPV18 DNA and E6 protein fluctuated consistently among women from normal histopathology to cancer. DNA load in E6-positive women was significantly higher than E6-negative for both types. Conclusions There is a type-dependent association between HPV16/18 DNA load and E6 protein; our study furthers the understanding of the natural history of cervical cancer.

HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p 0.001), but more specific (97.1% vs. 75.4%, p 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.

The zinc-finger transcription factors of the kruppel-like factor family (KLF) are critical in many physiological and pathological processes including cell proliferation, differentiation, inflammation, and apoptosis. Recently, there is increasing evidence that suggests these KLFs have an important role in fat biology. This review summarizes the role of KLFs in lipid metabolism, especially in adipogenesis, and reveals the relationship networks among members of KLF family in differentiation.

The relationship between HPV viral load and histological grades in the development of cervical cancer is in argument. It is helpful to better understand the association by quantitatively detecting viral load of HPV16, 18, and a pool of 12 other high-risk HPV type (OT) independently on the samples of precancer and cancer. A cross-sectional study was performed in five medical centers of China. Histological diagnosis made by local pathologists was adjudicated via a pathology expert panel. A fully automated real-time PCR test was used for the measurement of HPV16, 18, OT, and human β-globin gene. A total of 2,513 women [1,341 normal, 209 low grade intraepithelial lesion (LSIL), 392 high grade intraepithelial lesion (HSIL), 520 squamous cell carcinoma (SCC), and 51 adenocarcinoma (ADC)] were included. There is a linear increase in the total 14 HPV viral load with histological grade from normal to SCC. This trend was not observed in HPV18 infection but HPV16. The viral load for OT was low in normal, peaked in LSIL and HSIL, and declined in SCC and ADC. In the co-infection of HPV16 and HPV18, HPV16 viral load was significantly higher than HPV18 in LSIL and HSIL. In co-infection of HPV16 and OT, higher HPV16 viral load was also seen in SCC and ADC. Viral load of HPV16 increases with cervical lesion grade and is predominant in cervical cancer. HPV18 viral load is low in precancer, but going up in cancer. OT viral load shows inverse trend of HPV18. J. Med. Virol. 89:535-541, 2017. © 2016 Wiley Periodicals, Inc.

To explore the association between life style, diet intake and high risk human papillomavirus (HR-HPV) persistent infection among Chinese rural women living in Xinmi City, Henan Province.In 2010, a 3-year prospective study in which 2500 women were enrolled and screened by different HR-HPV DNA tests was conducted, part of women among them was followed and tested for HR-HPV DNA in 2012 and 2014. Furthermore, socio demographic factors, gynecological information and diet intake in the past 12 months were collected by self-designed questionnaire in 2014. A total of 721 women with complete test results were eligible for the final analysis. Study participants were divided into 3 groups (persistent infection group, transient infection group, and negative group) by HR-HPV status, and the association between life style, diet intake and HR-HPV persistence was evaluated using ordinal logistic regression model.The average age of 721 women included in the analysis was 50 years old. 141 women had HR-HPV persistent infection, 180 women had HR-HPV transient infection, and 400 women were negative for HR-HPV in 3 years. Age (Χ2 = 58.449, P0.001, P(trend)0.001), smoking (Χ2 = 6.981, P = 0.021), contraception method (Χ2 = 8.448, P = 0.015) , menopause (Χ2 = 35.712, P0.001), number of live births (Χ2 = 16.340, P0.001, P(trend)0.001), and the intake frequency of cereals (Χ2 = 17.937, P = 0.001) or others (Χ2 = 12.107, P = 0.017) varied significantly between women grouped by different HR-HPV status. Compared to women who were older than 59 years, women in the younger groups had a much lower risk of HR-HPV persistence (adjusted OR1 = 0.39, 95% CI 0.26 - 0.59, OR2 = 0.40, 95% CI 0.23 - 0.69, and OR3 = 0.28, 95% CI 0.12 - 0.68).Age is the main risk factor of HR-HPV persistent infection. Lifestyle, diet intake do not associate with HR-HPV persistence after adjustment by age.

// Lu-Lu Yu 1 , Wen Chen 1 , Xiao-Qin Lei 1 , Yu Qin 1 , Ze-Ni Wu 1 , Qin-Jing Pan 2 , Xun Zhang 2 , Bai-Feng Chang 2 , Shao-Kai Zhang 3 , Hui-Qin Guo 2 and You-Lin Qiao 1 1 Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 2 Department of Pathology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China 3 Department of Cancer Epidemiology, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Henan Office for Cancer Control and Research, Zhengzhou, P. R. China Correspondence to: Hui-Qin Guo, email: // You-Lin Qiao, email: // Keywords : cervical cancer; p16/Ki-67 dual staining; human papillomavirus; Chinese women; Pathology Section Received : December 23, 2015 Accepted : March 10, 2016 Published : March 23, 2016 Abstract Purpose: To analyze the clinical performance of p16/Ki-67 dual-stained cytology identifying high-grade cervical intraepithelial neoplasia (CIN2+) in Chinese women. Methods: 1079 women attending ongoing cervical cancer screening and 211 “enriched” women aged ≥30yrs with biopsy-confirmed CIN2+ from five Chinese hospitals were enrolled during year 2014-2015. Cervical specimens were collected for high-risk human papillomavirus (HR-HPV) DNA analysis, Liquid-based cytology (LBC) and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal result. Results: p16/Ki-67 positivity increased with histologic severity. It was 18.4%(183/996) in normal histology, 54.0%(34/63) in CIN1, 81.0%(34/42) in CIN2, 93.3%(111/119) in CIN3, 71.4% (5/7) in adenocarcinoma and 95.2%(60/63) in squamous cell carcinoma. Compared with the HR-HPV negatives, p16/Ki-67 expression was significantly higher in the HPV16/18 positive (OR: 35.45(95%CI: 23.35-53.84)) and other 12 HR-HPV types positive group (OR: 8.01(95%CI: 5.81-11.05). The sensitivity and specificity of p16/Ki-67 to detect CIN2+ in the entire population were 90.9% and 79.5%, respectively. In women with ASC-US and LSIL, sensitivity and specificity for detection of CIN2+ were 87.5% and 66.4%, respectively, with a referral rate of 43.8%. In women who tested positive for HR-HPV, sensitivity and specificity of dual-staining for detection of CIN2+ were 92.7% and 52.7%, respectively, and the referral rate was 68.7%. Conclusions: p16/Ki-67 dual-stained cytology provided a high sensitivity and moderate specificity to detect underlying cervical precancer and cancers in various settings, and might be considered as an efficient screening tool in China.

Background: An association between high-risk human papillomavirus (HR-HPV) oncoprotein expression and viral persistence has been suggested by the outcome of etiology studies, but there are no epidemiologic studies evaluating that link. Methods: We performed a 3-year prospective study in which 2,498 Chinese women ages 25 to 65 years were screened by six screening tests, including the OncoE6 Cervical Test (Arbor Vita Corporation) in 2011 (baseline). Six-hundred and ninety women who were positive for any of the tests and a random sample of 164 women with all negative results received colposcopy, and cervical specimens for the cobas 4800 HPV test (“cobas,” Roche Molecular Systems) were collected before colposcopy; of this group, 737 cervical specimens were collected to perform cobas and OncoE6 Cervical Test in 2014 (follow-up). Twenty-four cases of HPV16/18 E6 positives and 204 selected controls at baseline, 13 cases of HPV16/18 E6 positive and another 204 selected controls at follow-up were analyzed separately using unconditional logistical regression models to estimate ORs and 95% confidence intervals (CI). Results: Compared with women who were HPV16 E6 oncoprotein negative at baseline, women in the E6-positive group had a much higher risk of HPV persistence (adjusted OR, 54.64; 95% CI, 7.19–415.09) at 3-year follow-up; a statistically strong association was also found between HPV16/18 HPV persistence and E6 oncoprotein expression detected at follow-up (adjusted OR, 360.57; 95% CI, 28.30–4,593.55). Conclusions: A single detection of HPV16/18 E6 oncoprotein expression was strongly associated with viral persistence. Impact: HPV16/18 E6 oncoprotein constitutes a marker for risk of HPV persistence. Cancer Epidemiol Biomarkers Prev; 25(7); 1167–74. ©2016 AACR.

Volume 55, no. 2, p. 568–573, 2017, [https://doi.org/10.1128/JCM.02025-16][1]. The article was originally published on 25 January 2017 with a standard copyright line (“© 2017 American Society for Microbiology. All Rights Reserved.”). We elected to pay for open access for the article after

Coxsackievirus (CV) strains CVA2, CVA4, CVA5, and CVA10 were isolated from patients with hand, foot, and mouth disease during a 2009 outbreak in China. Full genome sequences for four representative strains, CVA2/SD/CHN/09 (A2SD09), CVA4/SZ/CHN/09 (A4SZ09), CVA5/SD/CHN/09 (A5SD09), and CVA10/SD/CHN/09 (A10SD09), were determined. Phylogenetic and recombination analyses of the isolates by comparison with human enterovirus A prototype strains revealed that genetic recombination occurred during cocirculation of the viruses. The A2SD09 and A4SZ09 strains were most closely related to their corresponding prototype strains in the capsid region but shared noncapsid sequences with each other. Similarly, strains A5SD09 and A10SD09 had serotype-specific homology for the capsid proteins but shared noncapsid sequences with each other. Phylogenetic analyses of the four isolates with homotypic strains showed that CVA2 strains were divided into five genotypes. The A2SD09 strain clustered with Mongolia strains isolated in 2003, forming genotype V. The A4SZ09 strain and other isolates from mainland China and Taiwan clustered with genotype III strains and are likely related to strains that circulated in Europe and Mongolia. The A5SD09 strain is closely related to other Chinese strains isolated in 2008. The A10SD09 isolate, together with other Chinese strains isolated since 2004, formed a distinct lineage that was likely imported from Japan and South Korea. This study shows that natural recombination is a frequent event in human enterovirus A evolution. More comprehensive surveillance of enteroviruses that focus not only on EV71 or CVA16 is needed for us to understand the molecular epidemiology of enteroviruses and to track recombination events which may ultimately affect the virulence of viruses during outbreaks.

Taking laser-guided seeker as an example, this paper analyses factors of jamming effect of the laser blinding. The mathematical model of the jamming effect is founded. The evaluation criterion and partial simulation results are given. Through analyzing the simulation results, it provides theoretical foundation for design and evaluation of the laser blinding system.

treatment-naive HIV/HCV coinfected patients in China across a broad spectrum of HCV genotypes. Methods: Population-basedNS3/4A sequencingwas completed for 826 HIV/HCV coinfected patients enrolled between 2004 and 2013, from 12 provinces across China. All patients were naive to antiretroviral treatment for HIV and any prior or investigational treatment for HCV. In-house primers for genotypes 1–6were used. NS3 sequences were aligned against reference sequences and mutations were manually identified in the following positions reported to confer resistance to HCV protease inhibitors: 36, 41, 43, 54, 55, 80, 109, 122, 132, 155, 156, 168, and 170. Findings: Overall, 81% (632/778) of all HCV sequences had at least one mutation associated with resistance to HCV protease inhibitors. Mutations were found in 4% (1/28) of genotype 1a, 44% (73/165) of genotype 1b, 100% (23/23) of genotype 2a, 100% (125/125) of genotype 3a, 100% (112/112) of genotype 3b, 99% (299/303) of genotype 6a, and none (0/22) of genotype 6n/u/v sequences. The Q80K mutation was present in 98% of genotype 6a sequences. Mutations with the potential to cause high-level decreased drug susceptibility are rare, occurring in only 0.8% of patients. Interpretation: The low frequency of high-level mutations associated with primary protease inhibitor drug resistance among most genotypes is encouraging, but the presence of theQ80Kmutation among patients with HCV genotype 6a is concerning given the association with decreased simeprevir efficacy in genotype 1a. Further phenotypic studies and clinical research are needed.