High-risk Human Papillomavirus Infection In Women Research Articles

Prevalence and Genotype Distribution of High-Risk Human Papillomavirus Infection in Women with Abnormal Cervical Cytology: A Population-Based Study in Shanxi Province, China.

PurposeHigh-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical cancer and there are notable differences in HR-HPV prevalence and genotype distribution in different populations. Women with abnormal cervical cytology are at increased risk of cervical cancer; however, the genotype distribution of HR-HPV in women with abnormal cervical cytology remains unclear.MethodsA total of 2,300 women with abnormal cervical cytology (from 39,988 women completing a baseline survey in a cohort established during June 2014 to December 2014) were enrolled in this study. All participants gave informed consent and completed a questionnaire about characteristics related to HPV infection. HPV genotypes were identified using flow-through hybridization, and cytology was assessed by the ThinPrep cytological test. Data were analyzed using SPSS 22.0 for Windows.ResultsThe overall prevalence of HR-HPV in the 2,300 women with abnormal cervical cytology was 32%, with single and multiple HR-HPV infections making up 70.2% and 29.8%, respectively. The top-five HR-HPV genotypes were HPV16 (13.5%), HPV58 (5.7%), HPV52 (4.9%), HPV53 (2.5%), and HPV51 (2.3%). The prevalence of HR-HPV in atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or higher was 30.8%, 36.5%, and 54.9%, respectively, showing an increasing trend with severity of cervical cytology (χ2trend=13.952, p<0.001). The prevalence of HPV16 and HPV33 increased significantly with the degree of cytological abnormality. HR-HPV infection risk was statistically higher in women aged 35–45 years, with low education, infrequent bathing, multiple gravidity, multiple parity, history of gynecological diseases, and premenopause.ConclusionHR-HPV infection in women with abnormal cervical cytology was 32%, and the top-five HR-HPV genotypes were HPV16, HPV58, HPV52, HPV53, and HPV51 in Shanxi Province, China. These results shed light on demographic and behavioral characteristics related to HR-HPV infection in women with abnormal cervical cytology and provide an insight for the development of HPV vaccines.

Deciphering the impact of genetic variation of the TLR9 gene in cervical cancer pathogenesis

Cervical carcinogenesis is a multi-step process associated with refractory infection by high-risk human papillomavirus (HPV) types. Only a minority of HPV infected women develop cervical intraepithelial neoplasia (CIN) or cervical cancer, indicating that HPV infection is not the sole risk factor to induce cervical cancer. The present study aimed to identify the association of toll like receptor 9 (TLR9) (2848C&amp;#62;T; rs352140) single neucleotide polymorphism (SNP) with cervical cancer in East Indian women. Study subjects comprised 71 women with histologically proven cervical cancer, and 100 women with benign cervical lesions. The case group included HPV 16 +ve subjects with malignancy. Among subjects with benign lesions, 43 were HPV 16 +ve (intermediate group) and 57 were HPV –ve (control group). TLR9 genotyping was performed using PCR RFLP. TLR9 expression was analyzed using real time PCR. For the C2848T polymorphism of TLR9, the TT genotype and the T allele frequency were significantly increased in the case group compared to those in the control group and the intermediate group. Our study suggests that the TLR9 C2848T polymorphism may be a genetic risk factor for cervical cancer and the progression from HPV infection to cervical cancer.

The role of body mass index in incidence and persistence of cervical human papillomavirus infection

PurposeThis study aimed to assess the association between body mass index and incident or persistent cervical high-risk human papillomavirus (hrHPV) infection. MethodsThis cohort study included 6809 women from the general Danish population who participated in two clinical visits (in 1991–1993 and in 1993–1995). Height and weight were measured by nurses, lifestyle data were obtained by structured interviews, and cervical cytology samples were obtained for hrHPV DNA testing. We conducted log-binomial regression to estimate risk ratios (RRs) with 95% confidence intervals (CIs) of incident and type-specific persistent hrHPV infection according to body mass index, adjusting for age, education, smoking, and the number of sexual partners in the past year. ResultsWe found no increased risk of incident hrHPV infection in women who were underweight (RRadjusted, 0.97; 95% CI, 0.64–1.48), overweight (RRadjusted, 0.98, 95% CI, 0.82–1.17), or obese (RRadjusted, 0.93; 95% CI, 0.63–1.36) compared with women of normal weight. The risk of hrHPV persistence was similar in overweight (RRadjusted, 0.98; 95% CI, 0.71–1.34) and obese (RRadjusted, 1.00; 95% CI, 0.56–1.79) women compared with women of normal weight, whereas underweight women had a lower risk (RRadjusted, 0.32; 95% CI, 0.11–0.95). ConclusionsOverweight and obesity were not associated with HPV incidence or persistence when adjusting for sexual behavior.

The Correlation between the Determination of Vaginal Micro-Ecological Composition and the Outcome of HPV Infection by High-Throughput Metagene Sequencing Information Technology on the Illumina Platform

ObjectiveTo study the correlation between vaginal micro-ecological composition and the outcome of human papillomavirus (HPV) infection by High-Throughput Metagene Sequencing Information Technology on the Illumina Platform, and to improve the efficiency of clinical infection detection. Methods: With the aid of Illumina high-throughput sequencing platform and sequence research method, the composition and diversity of vaginal microorganisms in high-risk HPV (HR-HPV) infected women and healthy women were analyzed. The differences in vaginal flora of HR-HPV infected women and healthy women were compared to explore the correlation between HR-HPV infection and vaginal flora. Results: The structure of vaginal flora in healthy women was relatively single, with Lactobacillus as the dominant genus, accounting for more than 80%. The structure of vaginal flora in women infected with HR-HPV was significantly different from that in non-infected women. The former had a significantly increased species diversity, which was mainly manifested by a decrease in Lactobacillus and an increase in Gardnerella vaginalis. Mycoplasma and Ureaplasma urealyticum might play a synergistic role in the initial stage of cervical lesions caused by HR-HPV infection. Conclusion: The prevention and treatment of mycoplasma and Ureaplasma urealyticum should be valued clinically to prevent the occurrence of HR-HPV infection and cervical lesions.

Genotypic distribution of human oncogenic papillomaviruses in sexually active women in Burkina Faso: Central, Central-Eastern and Hauts-Bassins regions.

Objective this study was conducted to determine the distribution of high-risk human papillomavirus (HR-HPV) genotypes in women in the general population of three regions of Burkina Faso. Method This multicenter, descriptive cross-sectional study involved 1321 sexually active women in five cities in three regions of Burkina Faso: Central, Central-Eastern and Hauts-Bassins regions. After collection of endocervical specimens, pre-cervical lesions were screened by visual inspection with acetic acid and lugol (VIA / VILI). HR-HPV genotypes were characterized by multiplex real-time PCR after extraction of viral DNA. Results The mean age of women was 31.98 ± 10.09 years. The HR-HPV infection in the three regions ranged from 26.16% to 43.26% with 35.42% as overall prevalence in women. The most common HR-HPV genotypes in descending order were: HPV 56, 52, 66, 59, 39, 51, 18, 35. The prevalence of bivalent vaccine genotypes (HPV16 / 18) was 7.83% against 63.78% of genotypes not covered by HPV vaccine; 36.32% (170/468) of women had multiple concomitant HR-HPV infections. Conclusion this study showed significant regional variation and high prevalence of HR-HPV infection in women. The predominant genotypes differ from those covered by available vaccines in Burkina Faso. These results will help guide our health policies towards better prevention of cervical cancer. The diversity of oncogenic genotypes is sparking a large-scale study in the West African sub-region, particularly in cases of cancer and the introduction of the nonavalent vaccine which includes HPV 52 found among the predominant genotypes in this study.

A demographic and clinico pathological study of HPV associated cofactors in the pathogenesis of cervical cancer

Aims: Cervical carcinogenesis is a multi-step process associated with refractory infection by highrisk human papillomavirus (HPV) types. Only a minority of HPV infected women develop cervical intraepithelial neoplasia (CIN) or cervical cancer, indicating that HPV infection is not the sole risk factor to induce cervical cancer. The present study aimed to identify the association of demographic and clinic pathological factors in persistent high risk HPV infections of cervix and progression to cervical cancer in East Indian women. Materials and Methods: Study subjects comprised 71 women with histologically proven cervical cancer, and 100 women with benign cervical lesions. The case group included HPV 16 +ve subjects with malignancy. Among subjects with benign lesions, 43 were HPV 16 +ve (intermediate group) and 57 were HPV – ve (control group). Demographic factors like age at diagnosis, age at first childbirth, parity, postmenopausal status, literacy, smoking and clinic pathological factors like type of cervical cancer and grading were correlated with HPV infections and cervical cancer. HPV status and HPV Type was confirmed by PCR based method, using specific primers. Results: There was significant association between HPV +ve individuals (both cases and intermediates) and increased parity, post menopause, increased age at diagnosis, decreased age at first childbirth, illiteracy and smoking. All individuals of the case group were HPV +ve, type 16 and most had poorly differentiated and stage III squamous cell carcinoma of the cervix. Conclusion: Our study suggests that demographic factors should be taken into account when screening for HPV infectivity and cervical cancer. Keywords: Cancer cervix, Demographic factors.

Methylation estimates the risk of precancer in HPV-infected women with discrepant results between cytology and HPV16/18 genotyping

BackgroundVigilant management of women with high-risk human papillomavirus (hrHPV) is necessary in cancer screening programs. To this end, we evaluated the performance of S5 (targeting DNA methylation in HPV16, HPV18, HPV31, HPV33, and human gene EPB41L3) to predict cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in a sample of hrHPV-infected women referred to colposcopy in the FRIDA Study, a large screening trial in Mexico. A nested case-control sample with women referred to colposcopy either by atypical squamous cells of undetermined significance or higher (ASCUS+) in cytology and/or positive for HPV types 16 or 18 was tested by S5. Seventy-nine cases of CIN2+ were age-matched to 237 controls without a diagnosis of CIN2+ (<CIN2). DNA from exfoliated cervical cells was bisulfite converted and PCR amplified for S5 targets, and methylation was quantified at specific cytosines by pyrosequencing.ResultsThe S5 classifier separated women with CIN2+ from <CIN2 with a highly significant area under the curve (AUC) of 0.75 (95% CI 0.69–0.82), while AUC for CIN3+ was 0.81 (95% CI 0.74–0.89). To optimize sensitivity and specificity for Mexico, an alternative S5 cutoff of 3.7 was implemented to account for overall higher methylation seen in our already triaged women. All three invasive cancers were detected by methylation or HPV16/18 but none by cytology. Sensitivity of S5 for CIN2+ was 62% (95% CI 50.4–72.7%), specificity was 73% (95% CI 66.9–78.5%), and adjusted PPV was 15.1% (95% CI 12.0–18.3%). In contrast, the crude sensitivity of HPV16/18 detection and cytology were 63.3% (95% CI 51.7–73.9%) and 57.0% (95% CI 45.3–68.1%) respectively; specificity was 29.1% (95% CI 23.4–35.3%) and 62.4% (95% CI 55.9–68.6%) respectively, while adjusted PPV was 6.4% (95% CI 4.9–8.1%) and 10.5% (95% CI 8.0–13.1%), respectively. Methylation testing could reduce colposcopy referrals by 30 to 50% with virtually no loss of sensitivity for CIN2+ and CIN3+.ConclusionsS5 testing on hrHPV-positive women significantly increased diagnostic information compared to triage by HPV16/18 plus cytology and appears to have clinical utility as an additional test to substantially lessen burdens on colposcopy.Trial registrationThe FRIDA Study is registered in ClinicalTrials.gov, number NCT02510027.

Association between the vaginal microbiome and high-risk human papillomavirus infection in pregnant Chinese women

BackgroundIn this study, the association between high-risk human papillomavirus (hrHPV) infection and the vaginal microbiome in pregnant women was evaluated in Chinese cohorts.MethodsThe vaginal bacterial composition of four groups, 38 hrHPV-infected pregnant women (PHR, n = 38), pregnant women without HPV infection (PN, n = 48), nonpregnant women with hrHPV infection (NPHR, n = 19) and nonpregnant women without HPV infection (NPN, n = 30), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3–4) using Illumina MiSeq.ResultsThe results revealed that both pregnancy and HPV infection can increase vaginal bacterial microbial richness and diversity, with the bacterial composition being most influenced by pregnancy. Lactobacillus was the most dominant genus among all samples. NPN samples were dominated by CST (community state type) III, mainly composed of Lactobacillus iners. Both pregnancy and hrHPV infection were accompanied by an increased proportion of CST I (dominated by Lactobacillus crispatus), as opposed to CST III. Bifidobacterium, Bacillus, Megasphaera, Sneathia, Prevotella, Gardnerella, Fastidiosipila and Dialister were found to be biomarkers for hrHPV-infected women, though different genera (Bifidobacterium, Megasphaera, Bacillus, Acidovorax, Oceanobacillus and Lactococcus) were associated with hrHPV-infected pregnant women.ConclusionsThis work uncovered a probable synergistic effect of hrHPV infection and pregnancy on the vaginal microbial composition. HPV infection in pregnant women was associated with a more complex and diverse microbial environment.

PC-10 Classical HLA alleles are associated with prevalent and persistent cervical high-risk HPV infection in African women

Background: Persistent cervical high-risk human papillomavirus (hrHPV) infection is a necessary cause of cervical cancer. However, the genetic factors underlying its risk are not well understood. We hypothesized that immunogenetic variation plays a role in hrHPV infection and persistence. Therefore, we conducted a study of classical HLA alleles and their association with hrHPV infection and persistence. Methods: We characterized HPV infection using SPF25/LiPA10 in Nigerian women at baseline and at 6 months follow-up visits in 2014. hrHPV infection was prevalent if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was performed with the Illumina Multi-Ethnic Genotyping Array. Classical HLA alleles were imputed from genotypes in the MHC region using the HLA genotype imputation with attribute bagging (HIBAG) algorithm. HLA association tests were conducted under additive genetic models. P values were adjusted for multiple comparisons with the false discovery rate (FDR) method. Results: The mean (±SD) age of the study participants was 38 (±8) years, 48% (247/517) were HIV negative, 24% (125/517) were hrHPV positive at baseline and 10% (51/517) had persistent hrHPV infections. In multivariate regression models adjusted for age, HIV status and the first principal component, DQA1*01:02 (OR 1.46; 95% CI: 1.07 to 1.97; P = 0.03). and DQA1*02:01 (OR 1.89; 95% CI: 1.12 to 3.15; P = 0.03) were positively associated with prevalent but not persistent hrHPV infections, while DQA1*05:01 was negatively associated with prevalent hrHPV (OR 0.45; 95% CI: 0.24 to 0.85; P = 0.03) but positively associated with persistent cervical hrHPV infections (OR 2.46; 95% CI: 1.27 to 4.77; P = 0.04). Four haplotypes (A*30:01 - DQA1*05:01, B*07:02 - C*07:02, B*07:02 - DQA1*05:01 and C*07:02 - DQA1*05:01) were significantly associated with prevalent cervical hrHPV infections and several haplotypes that included the DQA1*05:01 allelic variant (including B*15:10 - DQA1*05:01, DQA1*05:01 - DQB1*02:01 and DQA1*05:01 - DRB1*03:01) were significantly associated with persistent cervical hrHPV infections. Six amino acids located on the DQA1 gene were associated with prevalent but not persistent cervical hrHPV infections. Conclusions: This study, the first to investigate the association between HLA alleles and persistent hrHPV risk in African women, has identified important risk alleles that merit further study. Our findings provide new insights into risk factors for hrHPV infection in women of African ancestry.

Emerging role for Ureaplasma parvum serovar 3: Active infection in women with silent high-risk human papillomavirus and in women with idiopathic infertility.

Recently, there are controversial opinions on the presence of Mycoplasmas/Ureaplasmas as colonizers or pathogens, and on the use of a targeted therapy. This study aimed to characterize Mycoplasmas/Ureaplasmas infections in reproductive age women, including the acquisition of sexually transmitted (ST) pathogens and poor birth outcomes. A total of 646 healthy Italian women fulfilled the inclusion criteria including 521 infertile women, 65 pregnant women, and 60 fertile women with identified risk factors and symptomatic for vaginitis/cervicitis. Multiplex and quantitative molecular techniques and direct automatic DNA sequencing were performed to assess the genome structure of Mycoplasma/Ureaplasma species and ST infected pathogens. Ureaplasma parvum serovar 3 represented the predominant colonizer of the urogenital tract of this series and the unique species significantly associated with ST pathogens coinfection (p < 0.01). U. parvum load >104 bacteria/ml, suggestive of active infection, has been measured only in asymptomatic high-risk human papillomavirus infected women (24.3%) and in 40% of women with idiopathic infertility. To note, 16% of the follicular fluid from these idiopathic women resulted infected with U. parvum. In conclusion, the present study focused the attention on U. parvum serovar 3 as emerging microorganism in sexually active women that may have the benefit of targeted therapy.

The distribution and prevalence of human papillomavirus in women in mainland China.

We conducted a systematic review of the epidemiology of high-risk human papillomavirus (HPV) infections in mainland Chinese women to provide a general profile for the application and subsequent effectiveness evaluation of HPV vaccines. The PubMed, Web of Science, Medline (Ovid), China National Knowledge Infrastructure, and Wanfang databases were used for the literature search. The epidemiological studies published from January 2000 to June 2018 on high-risk HPVs in mainland Chinese women were investigated to systematically evaluate their epidemiological status. A total of 198 eligible studies were included. The results of meta-analysis showed that the overall infection rate of high-risk HPVs in mainland Chinese women was 19.0% (95% confidence interval [CI], 17.1%-20.9%), and the top 5 subtypes with the highest infection rates were 16, 52, 58, 53, and 18. The overall infection rates of cervical intraepithelial neoplasia I (CINI), CINII+, and cervical cancer patients were 59.6% (95% CI, 52.7%-66.4%), 84.8% (95% CI, 81.2%-88.5%), and 89.9% (95% CI, 86.6%-93.1%), respectively. The high-risk HPV infections and common subtypes in women of various ages in various regions were different, and the high-risk HPVs and subtypes in cervical cancer patients in various regions were also different. In conclusion, we systematically analyzed the HPV infections in women who live on the Chinese mainland. The epidemiology of high-risk HPVs in mainland Chinese women is basically consistent with that for the rest of the world. The HPV vaccines currently licensed in China could cover the major prevalent high-risk HPV subtypes in China, providing a basis for the development of a cervical cancer screening strategy and vaccine implementation in China.

Role of genomic DNA methylation in detection of cytologic and histologic abnormalities in high risk HPV-infected women.

Cervical cancer is the fourth most common malignancy affecting women worldwide. The development of disease is related to high-risk human papillomavirus (hrHPV) infection. Cytology has been the most recommended triage for primary cervical (pre)cancer screening despite relatively low sensitivity. Recently, genomic DNA methylation has been proposed as an additional marker to increase sensitivity for detecting cervical precancerous lesion. This study aimed to evaluate the performance of methylation status of three tumor suppressor genes (CADM1, FAM19A4, and MAL) and HPV genotyping in detection of cytologic and histologic abnormalities in cervical cancer screening. Two hundred and sixty samples with available frozen cell pellets including 70 randomly selected cases of negative for intraepithelial lesion or malignancy (NILM)&HPV-negative, 70 randomly selected cases of NILM&HPV-positive, and 120 cytologic abnormalities & HPV-positive from a population-based cervical cancer screening program (n = 7,604) were investigated for the DNA methylation pattern of CADM1, FAM19A4, and MAL. Of 120 cytologic abnormalities & HPV-positive cases, there were 115 available histologic results. HPV52 and HPV58 were most commonly found in histologic HSIL+. The methylation levels of CADM1, FAM19A4, and MAL were elevated with the severity of cytologic abnormality which significantly increased by 3.37, 6.65 and 2 folds, respectively, in cytologic HSIL comparing with NILM. A significant increase in methylation levels of these three genes was also observed in histologic HSIL+ compared with negative histology but only CADM1 showed a significant higher methylation level than histologic LSIL. Using the ROC curve analysis, DNA methylation levels of FAM19A4 performed best in differentiating high-grade cytology (ASC-H+ from NILM/ASC-US/LSIL), followed by CADM1 and MAL. Whilst the CADM1 methylation performed best in distinguishing histologic HSIL+ from negative/LSIL with an area under the ROC curve of 0.684, followed by MAL (0.663) and FAM19A4 (0.642). Interestingly, after combining high DNA methylation levels to HPV16/18 genotypes, rates of histologic HSIL+ detection were substantially increased from 25% to 79.55% for CADM1, 77.27% for FAM19A4, and 72.73% for MAL, respectively. The rate further increased up to 95.45% when at least one of three genes had a high methylation level. This suggests a possible role of genomic DNA methylation, especially CADM1, in detecting histologic HSIL+ lesions in combination with hrHPV testing.

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing, China.

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.

Developing and validating the Personal Risk of Oncogenic Human Papillomavirus infection score in US Women.

Determining risk scores for genital high-risk human papillomavirus (HRHPV) infection in women will support more efficient cervical cancer screening strategies. We developed and validated point scores to predict the likelihood of any genital HRHPV infection in women. We conducted the cross-sectional analysis in 2017 and used data from the 2005-14 US National Health and Nutrition Examination Survey (7337 women aged 25-59 years; 6300 women aged 30-59 years). Predictors were reproductive health practices, risk behaviors and demographic variables. The outcome was a positive result for any of the 21 genital HRHPV genotypes. The 2005-12 cohorts were used as training and testing sets to develop scores that best classified women into three risk groups: low risk (<20%), average risk (20-30%) and high risk (>30%). The 2013-14 cohort was used to validate the final scores. Two-point scores with six self-reported variables were created to predict any HRHPV risks for the two age groups: the Personal Risk of Oncogenic HPV (PRO-HPV25) for women aged 25-59 years old and PRO-HPV30 for women aged 30-59 years old. The scores were successfully prospectively validated, with good calibration with regards to the predicted and observed rates of HRHPV infection. The scores had fair discrimination (c-statistics: 0.67-0.68). The PRO-HPV risk scores can identify groups at low, average and high risk of genital HRHPV infection. This information can be used to prioritize women for cervical cancer screening in low-resource settings or to personalize screening intervals.

Primary study on the relationship between high-risk HPV infection and vaginal cervical microbiota

Objective: To understand characteristics of vaginal cervical microbiota in high-risk HPV (hrHPV) infected women and to uncover the relationship between hrHPV infection and vaginal cervical microbiota. Methods: All participants were randomly selected from Peking University First Hospital from September to October of 2017, including 5 subjects of control group, 5 cases of HPV16/18 group, 5 cases of other hrHPV infected group and 3 cases of cervical squamous carcinoma group. All subjects were required to fill in a questionnaire, and cervical and vaginal discharges were separately collected for microscopic examination and new generation sequencing targeting the variable region (V3-V4) of bacterial 16S rRNA gene. Results: Vaginal microbiota analysis: (1) 6 major phylum were found in vaginal microbiota:Firmicutes, Bacteroidetes, Fusobacteria, Actinobacteria, Tenericutes and Proteobacteria. Firmicutes contributed to the majority of normal vaginal flora, Bacteroidetes and Fusobacteria increased in hrHPV infected ones, while Fusobacteria showed significant difference in cervical carcinoma group. (2) Lactobacillus occupied most of normal vaginal flora while genus like Gardnella, Prevotella, Atopobium, Megasphaera and Sneathia increased in hrHPV infected subjects, Sneathia showed significant difference in cervical carcinoma group. (3) No significant difference had been calculated in Alpha diversity of four groups (P=0.073) . Cervical microbiota analysis: (1) Microbial diversity of cervical microbiota was higher than that of vaginal microbiota. (2) Significant difference had been found in Alpha diversity of four groups (P=0.046) . (3) Proteobacteria in normal cervical flora was much more than that in vagina, and Proteobacteria increased significantly in hrHPV infected cervical discharge. (3) Chlamydia increased significantly in cervical carcinoma group. Conclusions: The diversity of cervical microbiota is higher than that of vaginal microbiota. Change in cervical microbiota is more obvious than that of vagina in hrHPV infected subjects. Fusobacteria-Sneathia and Chlamydia significantly increase in cervical carcinoma group. Proteobacteria might relate to hrHPV infection.

Value of HPV 16/18 Genotyping and p16/Ki-67 Dual Staining to Predict Progression to HSIL/CIN2+ in Negative Cytologies From a Colposcopy Referral Population.

To assess the prognostic value of human papillomavirus (HPV) 16/18 genotyping and p16/Ki-67 dual staining cytology in high-risk HPV (hrHPV)-positive women with no lesion or minor abnormalities. We evaluated progression to high-grade squamous intraepithelial lesion/cervical intraepithelial neoplasia grades 2 to 3 or cervical cancer (HSIL/CIN2+), persistence/regression of hrHPV infection in women referred to colposcopy showing hrHPV infection, histology diagnosis different from HSIL/CIN2+, and negative cytology. HPV 16/18 genotyping and dual staining were performed in liquid-based cytologic specimens obtained on the first visit. Progression was observed in 16 (8.0%) of 200 women. Those with HPV 16/18 infection had an increased risk of progression compared with women infected by other hrHPV types, and they also showed more persistence. However, no association was observed between progression or persistence and the result of the dual staining. HPV 16/18-positive women with no lesions or minor abnormalities are at high risk of progression to HSIL/CIN2+ and hrHPV persistence.

Prevalence of high-risk HPV and its distribution in cervical precancerous lesions among 35-64 years old women who received cervical cancer screening in Beijing

Objective: To study the prevalence of high-risk HPV (HR HPV) in women who accepted cervical cancer screening in Beijing and its distribution in cervical precancerous lesions. Methods: From January 2014 to March 2015, all women aged 35-64 years old and received free screening in institutions of cervical cancer in Beijing were recruited. Stratified cluster random sampling method was used in selecting 31 091 women for gynecological examination and genotyping of HR-HPV. Those positive for HR-HPV (except for HPV 16/18) were examined for cervical cell. For those atypical squamous cells of uncertain significance (ASCUS) and above, who were positive for HPV 16/18 and with uncertain results for cervical cell, were transferred for colposcopy examination. For those with suspicious or abnormal results for colposcopy, were transferred for histopathology. The prevalence of HR-HPV, cervical cancer and precancerous lesions among the participants were analyzed. Results: Totally 31 091 women aged from 35-year-old to 64-year-old, with 44.3% (13 780 women) in the 35-49 age group and 55.7% (17 311 women) in the 50-64 age group. 66.1% (20 536 women) were rural women. The infection rate of HR-HPV was 7.4%(2 305 cases) among the women. High-risk infection rates of HPV except HPV 16/18 were 5.7% (1 758 cases), and multi-infection rate was 1.5% (477 cases). The highest infection rate was 7.9% (1 044 cases) among the 45-49 year-old and 50-54 year-old age groups (χ(2)=14.07, P=0.015). The rate in rural women was significantly higher than that of the urban women (6.2%, 507 cases; 7.9%, 1 798 cases) (χ(2)=25.75, P<0.001). The proportion of HPV16, HPV18, HPV52, HPV51, HPV58 was 17.0% (391 cases), 6.9% (161 cases), 8.6% (20 cases), 5.2% (12 cases) and 7.7% (18 cases), respectively. The detection rate of cervical cancer and precancerous lesions in the population was 395.6/100 000 (123 cases). In high-grade squamous intraepithelial lesions (HSIL), HPV16 and 18 infections accounted for 60.5% (72 cases) of all. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old group which were 1.5% (107 cases) and 25.2% (30 cases) (χ(2)=11.54, P=0.042). Conclusion: Top five types of HR-HPV infection in women who accepted cervical cancer screening in Beijing were HPV16, 18, 52, 51 and 58. The infection rate of HPV16 and 18 increased significantly in HSIL women. HPV16 infection rate and detection rate of HSIL were the highest in 50-54 year-old age group.

Effect of smoking on high-grade cervical cancer in women on the basis of human papillomavirus infection studies.

We aimed, in the present study, to measure the risk related to the high-grade cervical intraepithelial neoplasia grade 3 (CIN3) or worse (CIN3+) or worse/high-grade squamous intraepithelial lesions with respect to changes in human papillomavirus (HPV) and smoking status. A structured interview underwent for 7129 women. Then, we obtained their cervical cells and subjected to HPV testing. High-risk HPV infected and "no prevalent" cervical disease infected women were followed for cervical lesions up to 12 years (at baseline; n = 1531). Hazard ratios (HRs) for diagnosis of CIN3 (or worse) or worse/high-grade intraepithelial lesions were calculated along with the corresponding 95% confidence intervals (CIs). Among high-risk HPV-positive women, the conditions of long-term (more than 8 years) smokers and heavy (18 or more cigarettes/day) smokers are highly responsible for the increased risk for CIN3 or CIN3+. In the cases of persistent HPV-infected women, heavy smoking led to a higher risk for CIN3+ than those women who never smoked (HR, 2.31; 95% CI, 1.12-4.16). We concluded here that smoking leads to an enhanced risk of high-grade cervical lesions in persistent high-risk HPV-infected women. This makes a good understanding of smoking's role in cervical cancer.

High‐risk papillomavirus infection among women living with human Immunodeficiency virus: Brazilian multicentric study

Cervical cancer is an important health issue in Latin America. Although HPV infections can have spontaneous clearance, persistence of high-risk (HR) HPV is a risk factor for cervical cancer among women and it is even higher in HIV-infected women. To determine the prevalence of HR-HPV and risk factors among HIV-infected women attending reference services for HIV/AIDS in different regions of Brazil. Cross-sectional study conducted among HIV-infected women attended at referral care centers for HIV/AIDS in nine states of Brazil. Women from 18 to 49 years that accept to participate and were not pregnant at the time of the approach were recruited for the study. The HPV screening was realized using qPCR in closed system, in vitro Diagnostic, COBAS® -HPV Roche. The cytology results were available by the Bethesda System. A total of 802(89.1%) from the selected women agreed to participate in the study. Median age was 39(Inter quartile range [IQR34-46]) years and median education was 9(IQR6-11) years. General prevalence of HR-HPV was 28.4%(228/802). HPV-16 prevalence rate was 8.1%(65/802), HPV-18 was 3.7%(30/802) and other types of HR-HPV were 23.6% (189/802). Risk factors for HR-HPV infection in the multivariate logistic regression analysis were: age ranging from 18 to 34 years (OR = 1.43[95%CI:1.18-1.75]), illicit drugs use (OR = 1.61[95%CI:1.10-2.42]) and abnormal cervical cytology (OR = 1.56[95%CI:1.34-1.81]). Results showed a prevalence rate of 28.4% of HR-HPV infection in women living with HIV in Brazil. These infections were significantly associated with having less than 35 years old, illicit drug use and abnormal cervical cytology.

Prevalence of and Associated Risk Factors for High Risk Human Papillomavirus among Sexually Active Women, Swaziland.

BackgroundHigh risk human papillomavirus (hr-HPV) infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs) such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland.MethodsA total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays.ResultsThe overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8–49.5). Of hr-HPV infected women, 12.4% (95%CI: 8.6–17.5) were HPV16-positive, 13.8% (95%CI:12.0–15.8) were positive for HPV18/45, 26.7% (95%CI: 24.2–29.3) for HPV31/33/35/52/58, 7.6% (95%CI: 7.6–11.9) for HPV51/59 and 11.0%, (95%CI: 7.9–15.3) for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7–46.2). HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043–7.8, p<0.001). Overall hr-HPV/HIV co-infection was 24.4% (95%CI: 20.3–29.1) which was significantly higher among younger age groups (p<0.001). Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus -negative women (27.7% and 12.7% respectively, p<0.001). The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6–7.1, OR = 4.6, 95%CI: 2.8–7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3–13.4, p<0.021 respectively).ConclusionThe prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among youth and HIV infected people.