HR-HPV Group Research Articles

A Crosstalk Analysis of high-risk human papillomavirus, microbiota and vaginal metabolome in cervicovaginal microenvironment

The microbial community has a profound effect on the host microenvironment by altering metabolites. Persistent high-risk human papillomavirus (HRHPV) infection has been implicated as contributors to the initiation and progression of cervical cancer, but the involved mechanisms are unknown. Assessing the metabolic profile of the cervicovaginal microenvironment has the potential to reveal the functional interactions among the host, metabolites and microbes in HRHPV persistence infection and progression to cancer. The vaginal swabs of women were collected and divided into three groups according to the HPV HybridenPture DNA test (HC2). The participants, include 9 who were categorized as HPV-negative, 8 as positive for HPV16, and 9 as positive for HPV18. 16S rRNA gene sequencing and metabolomics analyses were applied to determine the influence of the vaginal microbiota and host metabolism on the link between HPV and cervicovaginal microenvironment. These findings revealed that HRHPV groups have unique metabolic fingerprints that distinguish them from heathy controls. We showed that HRHPV affects changes in microbial metabolic function, which has important implications for the host. Our study further demonstrated metabolite-driven complex host-microbe interactions and assist in understanding the alterations in the HRHPV-induced cervicovaginal microenvironment.

Aptima HPV Genotypes in Abnormal Cervical Samples in Different Age Groups - Implication on Vaccination Strategies.

Persistent infection with high-risk human papillomavirus (hr-HPV) types is associated with high-grade cervical abnormalities. The aim of the study was to find most hr-HPV types causing persistent infection in abnormal cytological samples using Aptima HPV testing and discuss the compatibility of the Gardasil 9 vaccine in targeting most types. The study was conducted in a cytology laboratory in a tertiary hospital. This is a retrospective observational study. Cytology and HPV Aptima test reports were obtained for abnormal cervical samples for a 6-year period. Pearson Chi-square test. Reports of 2834 abnormal cervical samples were analyzed. Aptima testing was positive in 21% of samples, including 92% of squamous cell carcinoma (SCC), 76.4% of the high-grade squamous intraepithelial lesion (HSIL), 52% of low-grade squamous intraepithelial lesion (LSIL), 40% of adenocarcinoma (ADC), and 21% of atypical squamous cells that cannot exclude HSIL (ASC-H). The Aptima other hr-HPV group was most common (60%), HPV16 was 26%, HPV18/45 was 9.6%, and double HPV infection was 4.3%. HPV16 was the most common infection in HSIL+ cases. HPV infection was most common in age groups (30-39) and (40-49), and a shift to age groups (50-59) and ≥60 was seen in HSIL+ cases. This study is the first of its kind in correlating age with hr-HPV and cytology findings in the Middle East and adds to previous knowledge related to the prevalence and Aptima testing of HPV. The outcome could be used as a baseline for the Gardasil 9 vaccine and for the assessment of its effectiveness after three or five years from initiation.

Evaluation of malignant potential based on infection with high-risk human papillomaviruses 16, 52, and 58 in the uterine cervix.

e17511 Background: The high-risk human papilloma virus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. Generally, gynecologists recommend medical interventions for patients diagnosed with HSIL or higher. Previous studies have evaluated genotype-specific risk for carcinogenesis. However, the genotype-specific risk remains still unclear due to some limitations of those studies. This study aimed to evaluate the malignant potential of the three most prevalent HR-HPVs in Korea. Methods: Patients who underwent uterine cervical conization were included. They had received HPV test within a year before the surgery and those exhibiting concurrent multiple infections with HR-HPVs were excluded. Of single infections with HR-HPV, the three most prevalent HR-HPVs were included to analyze. To evaluate their malignant potential, CIS+, including carcinoma in situ (CIS) and invasive carcinoma, was categorized in each HR-HPV group. The ratios of pathologic diagnoses and odds ratios for malignant potential were evaluated between the three most prevalent HR-HPVs. Results: Totally 230 patients were found to have a single infection with HR-HPV16, HR-HPV52, or HR-HPV58. Of the included patients, 119 (51.7%), 60 (26.1%), and 51 (22.8%) were noted to be infected with HR-HPV genotypes 16, 52, and 58, respectively. CIS was diagnosed in 59 (49.6%), 27 (45.0%), and 25 (49.0%) patients in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.839). Invasive carcinoma, regardless of histology such as squamous cell carcinoma or adenocarcinoma, was diagnosed in 8 (6.7%), 1 (1.7%), and 1 (2.0%) patient in the HPV16, HPV52, and HPV58 single infection groups, respectively ( p = 0.187). The CIS+ ratio was not significantly different among the HPV16, HPV52, and HPV58 single infection groups (67 [56.3%] vs. 28 [46.7%] vs. 26 [60.0%], [ p = 0.460]). Conclusions: Among the Korean women with single HR-HPV infection, HPV16, HPV52, and HPV58 were the three most common genotypes, in descending order. Although HPV16 was the most prevalent among the three, its malignant potential was not significantly different from those of HPV52 and HPV58 in the uterine cervix. This result supports the need for a nine-valent vaccine against HR-HPVs, covering HPV52, HPV58, and HPV16.

Cervical microbiota dysbiosis associated with high-risk Human Papillomavirus infection.

High-risk Human Papillomavirus (HR-HPV) genotypes, specifically HPV16 and HPV18, pose a significant risk for the development of cervical intraepithelial neoplasia and cervical cancer. In the multifaceted cervical microenvironment, consisting of immune cells and diverse microbiota, Lactobacillus emerges as a pivotal factor, wielding significant influence in both stabilizing and disrupting the microbiome of the reproductive tract. To analyze the distinction between the cervical microbiota and Lactobacillus-dominant/non-dominant status of HR-HPV and non-infected healthy women, sixty-nine cervical swab samples were analyzed, included 44 with HR-HPV infection and healthy controls. All samples were recruited from Human Papillomavirus-based cervical cancer screening program and subjected to 16s rRNA sequencing analysis. Alpha and beta diversity analyses reveal no significant differences in the cervical microbiota of HR-HPV-infected women, including 16 and 18 HPV genotypes, and those with squamous intraepithelial lesion (SIL), compared to a control group. In this study we identified significantly lower abundance of Lactobacillus mucosae in women with HR-HPV infection compared to the control group. Furthermore, changes in bacterial diversity were noted in Lactobacillus non-dominant (LND) samples compared to Lactobacillus-dominant (LD) in both HR-HPV-infected and control groups. LND samples in HR-HPV-infected women exhibited a cervical dysbiotic state, characterized by Lactobacillus deficiency. In turn, the LD HR-HPV group showed an overrepresentation of Lactobacillus helveticus. In summary, our study highlighted the distinctive roles of L. mucosae and L. helveticus in HR-HPV infections, signaling a need for further research to demonstrate potential clinical implications of cervical microbiota dysbiosis.

Human papillomavirus in women infected with human immunodeficiency virus: association with viral load and lymphocyte count.

Women living with human immunodeficiency virus are at an increased risk of developing cancers related to human papillomavirus (HPV). Thus, it is important to combine clinical assessments, serological screening, and HPV data for planning prevention policies. This study aimed to identify HPV and its specific types in the cervical, anal, and oral mucosa of HIV-seropositive women, associating it with viral load and lymphocyte count. Sociodemographic characteristics, health data (CD4+ and CD8+ T cell counts and viral load), and biological samples (cervical, anal, and oral) were collected from 86 HIV-positive women undergoing antiretroviral therapy. Data were classified according to the presence or absence of HPV-DNA, HPV-DNA presence at one or more anatomic sites, and level of oncogenic risk, considering low- and high-risk oncogenic HPV-DNA groups. The presence of HPV in the cervicovaginal site was 65.9%, 63.8% in anal canal, and 4.2% in oral mucosa. A viral load ≥75 HIV copies/mL was associated with the presence of HPV-DNA. There was an association between viral load and the low-risk HPV or high-risk HPV groups. We found a high prevalence of HPV infection in HIV-seropositive women, particularly in the cervical and anal mucosa, with viral load ≥75 HIV copies/mL being associated with HPV-DNA presence.

Analysis of the correlation between cervical HPV infection, cervical lesions and vaginal microecology.

Vaginal microbiota is involved in human papillomavirus (HPV) infection and cervical cancer (CC) progression, and the specific changes in vaginal microbial composition during this process remains uncertain. This study aimed to observe the changes in the specific composition of vaginal microorganisms in different cervical lesions and identify biomarkers at different stages of lesions. In this study we used the illumina high-throughput gene sequencing technology to determine the V4 region of 16SrRNA and observed the vaginal microbial composition in different cervical lesions. The vaginal microbiota of patients with high-risk HPV infection and cervical lesions is significantly different from that of the normal population, but there is no significant difference in the richness of vaginal microbes. The diversity of vaginal species in CC patients is higher than that in high-risk HPV infection or CIN patients. The main manifestation is an increase in the diversity of vaginal microbes, a decrease in the relative abundance of cyanobacteria and Lactobacillus, and an increase in the relative abundance of dialister, peptonephila and other miscellaneous bacteria. There are characteristic vaginal biomarker in normal women, high risk HPV patients and CC patients. In detail, the biomarker in the normal group was varibaculum, the biomarker in the high-risk HPV group was saccharopolyspora, the biomarker of the CC group was the Proteobacteria, Corynebacterium, Coprococcus, Peptococcus and Ruminococcus. The study indicated that the compositions of vaginal microbes in different cervical lesions is different. The vaginal microbial composition has a certain diagnostic effect on healthy women, patients with high-risk HPV infection and cervical lesions. These microbes may serve as potential biomarkers for CC. It also provided an effective way for the treatment of HPV infections and cervical lesions.

Prevalence and risk factors associated with high-risk human papillomavirus infection among women living with HIV (WLWH) at a tertiary health facility in Accra, Ghana.

Women living with HIV (WLWH) have high risk of developing cervical cancer. High- risk Human papillomavirus (hrHPV) is the single most important cause of cervical cancer. Vaccination for and early detection of pre-malignant cervical changes, through cervical cancer screening contributes to prevention of cervical cancer. This study sought to determine the prevalence of HPV among WLWH, genotypes present and the risk factors associated with cervical cancer development. An analytical cross-sectional study of 250 sexually active women aged 18 years and above, attending HIV clinic at a tertiary health facility in Accra. Demographic data collection and risk factor assessments were done using interviewer-administered questionnaire, and patient records. Cervical swabs were collected and tested for HPV using real-time PCR assays. Genotype analysis was performed on 92 samples. Descriptive statistics and logistic regression analysis were used to establish associations between hrHPV and risk factors among WLWH. Approximately 60% of study participants tested positive for HPV. The prevalence of hr-HPV among WLH was 44.4%. Factors identified to be protective of hrHPV were employment (AOR = 0.19, 95% CI = 0.06, 0.56, p = 0.003) and highly active antiretroviral therapy (HAART) Tenofovir-Lamivudine-Ritonavir-Lopinavir (TLRL) (AOR = 0.30, 95% CI = 0.09, 0.95, p = 0.04). Women with HIV diagnosis within 6 to10 years (AOR = 4.89, 95% CI = 1.05, 22.70, p = 0.043) and diagnosis >10 years (AOR = 8.25, 95% CI = 1.24, 54.84, p = 0.029) had higher odds of hrHPV. Approximately 25% of samples analysed tested positive for hr-HPV group 1 (genotypes 16, 18, 31, 33, 35, 39, 45,51, 52, 56, 58, 69) and 46.8% for multiple HPV genotypes. A high prevalence of genotypes that include high risk genotypes 16 and 18 and multiple HPV infections was found among WLWH. Almost half of the women screened had high-risk HPV and were prone to cervical cancer without their knowledge. Regular HPV screening is recommended for high-risk patient groups.

A comparative analysis of cycle threshold (Ct) values from Cobas4800 and AmpFire HPV assay for triage of women with positive hrHPV results

BackgroundTo compare the triage performance of HPV viral loads reflected by cycle threshold values (CtV) from two different HPV testing assays: the PCR based Cobas4800 and the isothermal amplification based AmpFire assay.MethodsWe used the data from a sub-study of The Chinese Multi-Center Screening Trial and analyzed the data of the cases positive in both Cobas4800 and AmpFire assays with recorded CtV. Spearman’s correlation was applied to analyze the association between CtV from AmpFire and Cobas4800 assays, as well as the correlation between CtV and the histological lesion grades. The 50th percentile of CtV was used as the cutoff to construct triage algorithms for HPV-positive cases. McNemar’s test was used to analyze the differences in sensitivity and specificity for detecting CIN2 + and CIN3 + in different triage algorithms.ResultsFour hundred forty-six HPV positive women who had consistent HPV results from Cobas4800 and AmpFire in terms of the HPV genotype and reported Ct values were included in the analysis. The mean CtV of hrHPV tested by Cobas4800 and AmpFire were linear correlated. Direct association were showed between the severity of cervical lesions and the HPV viral loads reflected by CtV of hrHPV, HPV16, non-16/18 hrHPV and A9 group from both assays. HPV16/18 genotyping combined with low-CtV for non-16/18 hrHPV, especially A9 group, were demonstrated to be satisfactory in the sensitivity and specificity for detecting CIN2 + or CIN3 + .ConclusionCt value represented a good triage marker in both PCR-based and isothermal amplification HPV detection.

Correlation of immediate prevalence of cervical squamous cell precancers and cancers with HPV genotype and age in women with LSIL cytology: A retrospective analysis of 1617 cases.

To evaluate the immediate risk of cervical squamous cell precancers and cancers in women with low-grade squamous intraepithelial lesion (LSIL) cytology according to different high-risk human papillomavirus (hrHPV) results and age stratification. The study included 1617 women with LSIL cytology and underwent simultaneous Aptima HPV genotyping (E6/E7 mRNA test) followed by cervical biopsy. Among 1317 hrHPV positive cases, other 11 types of hrHPV were the most frequent (68.8%), followed by HPV16 (11.1%), HPV18/45 (4.1%), and HPV16/HPV18/45 (0.5%). Compared to other groups, HPV18/45 positive group and other 11 types of hrHPV group showed significantly higher prevalence of intraepithelial neoplasia grade (CIN)1 (p < .0001), while HPV16 positive and HPV16/HPV18/45 dual positive groups showed significantly higher prevalence of CIN2/3 (p < .0001). In addition, hrHPV positive, 25-39 years-old age group showed a significantly higher prevalence of CIN1 (p = .032) than the other age groups. Furthermore, CIN1 prevalence was significantly higher in patients under 40 or 50 years of age than in those over 40 or 50 years of age (p = .005 and p = .011, respectively). However, there was no significant difference among the different age groups in CIN2/3 prevalence in women with LSIL cytology. In southern Chinese women population, LSIL cytology carries very low immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3) in general. However, HPV16 positive and HPV16/HPV18/45 dual positive indicated a higher immediate risk of high-grade squamous intraepithelial lesions (HSIL) (CIN2/3). Age is not an immediate risk factor in this patient population for high-grade squamous lesions or SCC. These results are similar to data from cytology laboratories in the United States and other international settings, therefore strongly support the usage of ASCCP guidelines in this patient population.

Correlation between vaginal flora and cervical immune function of human papilloma virus-infected patients with cervical cancer.

To analyse the correlation between vaginal flora and cervical immune function of HPV-infected patients with cervical cancer. Six hundred females with genital tract infections treated in Xuzhou Hospital of Traditional Chinese Medicine from January 2014 to December 2016 were selected and divided into a high-risk HPV group (n=246) and a control group (n=354). The vaginal flora and human T lymphocyte subsets (CD3+, CD4+, CD8+) were detected. Multivariate logistic regression analysis was performed to explore the risk factors for HPV infection. The numbers of CD4+ and CD4+/CD8+ T cells of the high-risk HPV group were significantly lower than those of the control group (P<0.05). The two groups had similar numbers of CD3+ and CD8+ T cells. In the high-risk HPV group, the positive rates of Lactobacillus, Chlamydia trachomatis, Mycoplasma hominis, mycetes, Ureaplasma urealyticum and bacterial vaginosis were significantly higher than those of the control group (P<0.05). There was no significant difference in the positive rates of trichomonads between the two groups. Multivariate logistic regression analysis revealed that C. trachomatis and U. urealyticum were independent risk factors for high-risk HPV infection (P<0.05). High-risk HPV infection in patients with cervical cancer was associated with vaginal flora and immune function. C. trachomatis and U. urealyticum were independent risk factors for high-risk HPV infection.

Immediate histopathologic correlation in Turkish population with negative cytology and high-risk human papillomavirus positivity: A retrospective analysis of high-risk human papillomavirus genotype and stratified by age.

According to the American Society of Colposcopy and Cervical Pathology (ASCCP) recommendations, regardless of age, women with high-risk infections other than human papillomavirus 16/18 positivity (other hrHPV) and negative cytology should not be referred directly to colposcopy. Several studies compared detection rates of ≥high-grade squamous intraepithelial lesion (HSIL) between HPV 16/18 ± 45, and other hrHPV types on colposcopic biopsy. We designed a retrospective study to determine the presence of ≥HSIL in colposcopic biopsy in women with negative cytology and hrHPV positivity during the years 2016-2022. HPV 16/18/45 had a PPV of 43.8%, while other hrHPV types had a PPV of 29.1% for a tissue diagnosis of ≥HSIL. For a tissue diagnosis of ≥HSIL detection, there was no statistically significant difference between the PPV of other hrHPV and HPV 16/18/45 in patients ≥30. There were only two cases with a tissue diagnosis of ≥HSIL in the other hrHPV group of women under 30 years of age. We suggested that the follow-up recommendations of ASCCP for patients above the age of 30 with negative cytology and other hrHPV positivity may not be fully applicable to countries like Turkey with a different healthcare environment. Referring to patients ≥30 who had other hrHPV positivity and negative cytology to direct colposcopy may be clinically beneficial, particularly in populations where a colposcopic examination is easy and inexpensive.

Women with Cervical High-Risk Human Papillomavirus: Be Aware of Your Anus! The ANGY Cross-Sectional Clinical Study.

Simple SummaryHigh-risk HPV (HR-HPV) infection is an established risk factor of cervical cancer. Cases of anal cancer are increasingly observed in women. Since anal infection by HR-HPV is also a risk factor for anal cancer, the aim of this study was to investigate the relation between cervical and anal HPV and dysplasia, as their interaction remains unclear. The present study identified anal HR-HPV as an independent risk factor for patients with cervical HR-HPV (OR 3.3, CI 1.2–9.0, p = 0.02). This finding emphasizes the importance of concomitant screening of the anal region in case of cervical HR-HPV.Anogenital human papillomaviruses (HPV) are highly prevalent in sexually active populations, with HR-HPV being associated with dysplasia and cancers. The consequences of cervical HPV infection are well-known, whereas those of the anus are less clear. The correlation of cervical and anal HPVs with the increasing number of anal cancers in women has not been studied yet. The objective of our prospective study was to determine whether cervical and anal HPV correlated in a cohort of women recruited in a university hospital in Switzerland. Recruitment was conducted in the gynecology clinic, the colposcopy clinic, and the HIV clinic. Cervical and anal HPV genotyping and cytology were performed. Overall, 275 patients were included (360 were initially planned), and among them, 102 (37%) had cervical HR-HPV. Patients with cervical HR-HPV compared to patients without cervical HR-HPV were significantly younger (39 vs. 44 yrs, p < 0.001), had earlier sexual intercourse (17.2 vs. 18.3 yrs, p < 0.01), had more sexual partners (2.9 vs. 2.2, p < 0.0001), more dysplastic cervical cytology findings (42% vs. 19%, p < 0.0001) and higher prevalence of anal HR-HPV (59% vs. 24%, p < 0.0001). Furthermore, the HR-HPV group reported more anal intercourse (44% vs. 29%, p < 0.015). Multivariate analysis retained anal HR-HPV as independent risk factor for cervical HR-HPV (OR3.3, CI 1.2–9.0, p = 0.02). The results of this study emphasize that it is of upmost importance to screen women for anal HR-HPV when diagnosing cervical HR-HPV.

Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District, Chengdu City

To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.

Comparison of cytopathologic findings in patients with negative Pap test and positive high-risk HPV infection among three groups.

Comparison of colposcopy-guided biopsy and endocervical cytologic (ECC) results in patients with negative Papanicolaou (Pap) and positive high-risk (HR) HPV tests in the three groups of HPV 16/18, non-16/18 HR-HPV (other HR-HPV), and concurrent infection of either HPV 16/18 and at least one subtype of other HR-HPVs. This cross-sectional study was conducted among women aged 30-65 who had negative Pap and positive HR-HPV DNA tests. Pap test was performed using liquid cytology. For HPV DNA testing, the polymerase chain reaction (PCR) method was used. Among 394 participants, 111 (28.2%) were in the HPV 16/18, 226 (57.4%) in the Other HR-HPV, and 57 (14.4%) in the concurrent group. The mean age of participants was 35.71 ± 7.1years. Cervical intraepithelial neoplasia (CIN) grade 2/3 were seen in 29 (26.1%) patients of HPV 16/18, 60 (26.5%) of other HR-HPV, and 18 (31.6%) of concurrent infection group (P = 0.593). HPV 52 was the most common subtype in the other HR-HPV group (15%). The risk of high-grade CIN lesions in patients with negative Pap test and positive other HR-HPV was not significantly less than patients with positive HPV 16/18. Besides, the risk of losing the patients to 1-year follow-up seems high.

The association of telomere maintenance and TERT expression with susceptibility to human papillomavirus infection in cervical epithelium.

The role of telomerase reverse transcriptase (TERT) induction and telomere maintenance in carcinogenesis including cervical cancer (CC) pathogenesis has been well established. However, it remains unclear whether they affect infection of high-risk human papillomavirus (hrHPV), an initiating event for CC development. Similarly, genetic variants at the TERT locus are shown to be associated with susceptibility to CC, but it is unclear whether these SNPs modify the risk for cervical HPV infection. Here we show that in CC-derived HeLa cells, TERT overexpression inhibits, while its depletion upregulates expression of Syndecan-1 (SDC-1), a key component for HPV entry receptors. The TCGA cohort of CC analyses reveals an inverse correlation between TERT and SDC-1 expression (R = -0.23, P = 0.001). We further recruited 1330 females (520 non-HPV and 810 hrHPV-infected) without CC or high-grade cervicalintraepithelial neoplasia to analyze telomeres in cervical epithelial cells and SNPs at rs2736098, rs2736100 and rs2736108, previously identified TERT SNPs for CC risk. Non-infected females exhibited age-related telomere shortening in cervical epithelial cells and their telomeres were significantly longer than those in hrHPV-infected group (1.31 ± 0.62 vs 1.19 ± 0.48, P < 0.001). There were no differences in rs2736098 and rs2736100 genotypes, but non-infected individuals had significantly a higher C-allele frequency (associated with higher TERT expression) while lower T-allele levels at rs2736108 compared with those in the hrHPV group (P = 0.020). Collectively, appropriate telomere maintenance and TERT expression in normal cervical cells may prevent CC by modulating hrHPV infection predisposition, although they are required for CC development and progression.

P16INK4A Expression in Condyloma Acuminata Lesions Associated with High-Risk Human Papillomavirus Infection.

Objective:The objective of this study was to discover the possible correlation between p16INK4A expression and the LR/HR-HPV infection in condyloma acuminate (CA) lesions. Materials and Method:This cross-sectional study was conducted during January-December 2017 on 33 CA patients. The expression of p16INK4A was detected by immunohistochemistry (IHC) staining. The positive interpretation was carried out by scoring which score 0 was negative, score 1 was sporadic, score 2 was focal, and score 3 was diffuses. The HPV genotypes were identified by reverse line blot, and 40 genotypes of HPV detected, including HR-HPV (HPVs 16, 18, 26, 31, 33,35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, 68a, 68b, 69, 73, and 82) and LR-HPV (HPVs 6, 11, 40, 42, 43, 44, 54, 55, 61, 62, 64, 70, 71, 72, 81, 83, 84, 87, 89, and 90). Results:The expression of p16INK4A was significantly correlated with HR-HPV infection. Patients infected with HR-HPV had 0.644 times higher possibility to express p16INK4A gene compared to those infected with LR-HPV. LR-HPV genotypes detected in CA patients were HPVs 6, 11, 42, 61, 54, 81, 87, 89, and 90 and HR-HPV genotypes were HPVs 18, 26, 45, 51, 52, 67, 68B, 69, and 82. LR-HPV was found in 19/33 of patients and HR-HPV was in 14/33 of patients. The expression of p16INK4A in CA lesions was diffuse in15.2% of patients, was focal in 24.2% of patients , was sporadic in 39.4% of patients were, and was negative in 21.2% of patients . In LR-HPV group, there was no diffuse expression, focal expression was observed in 15.8%, sporadic in 47.4%, and negative in 36.8%, while in HR-HPV group, p16INK4A expression was detected in all lesions , in a way that its expression was diffuse in 35.7%, focal in 35.7%, and sporadic in 28.6%. Conclusion:IHC is a routine method in histopathological diagnosis, therefore the detection of p16INK4A expression by IHC can be used as a biomarker for HR-HPV infection diagnosis.

Prevalence of active infection by herpes simplex virus type 2 in patients with high-risk human papillomavirus infection: A cross-sectional study.

The aim is to determine the prevalence of active infection by herpes simplex virus type 2 (HSV-2) among Mexican women with high-risk human papillomavirus (HR-HPV) cervical infection, recruited from public gynecology and colposcopy services. In a cross-sectional study, HSV-2 antibodies, HSV-2 DNA, and HR-HPV DNA were quantified. Significant differences in HSV-2 seroprevalence and HSV-2 active infection rates were found between negative and positive HR-HPV cases. HSV-2 seroprevalence was 28.15% and 16.1% (P = .0001), while HSV-2 active infection rates were 6.83% and 0.62% (P = .001) for positive and negative HR-HPV groups, respectively. The risk of HSV-2 seropositivity was 1.7 times greater for HR-HPV-positive cases (P = .02). Similarly, HR-HPV-positive cases were nine times more likely to have an HSV-2 active infection than HR-HPV-negative cases (P = .03). High HSV-2/h-HPV coinfection rates were observed among women recruited from public gynecology and colposcopy services. The main factors related to an HSV-2 active infection are a history of risky sexual behavior and HR-HPV infection. The prevalence of HSV-2 active infection among positive HR-HPV subjects indicate that these infections constitute an important group of STIs in Mexico.

P521 Infection of the anal canal by human papillomavirus in Crohn’s disease

Abstract Background Compare the frequency of subclinical papillomavirus (HPV) in the anal canal os Crohn′s disease (DC) patients to a control group by smear cytology and polymerase chain reaction (PCR) and hybridisation and to assess whether there is correlation with the presence of immunosuppression and anal manifestations of the disease, besides establishing the agreement between the two diagnostic methods used. Methods Two groups were selected, one with DC and others to be the control population. All the individuals were submitted to smear cytology (two brushes inserted in sequence in the anal canal) and a third one preserved for molecular analysis (PCR and hybridisation). The cytology was classified according to Bethesda criteria as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL). The molecular analysis was considered with HPV present or absent and types 16 and high-risk HPV group identified. Results During sixteen months, 104 patients underwent anal cytology collection for smear preparation and HPV molecular method detection. The control group consisted of 41 individuals and the DC of 63 patients (32 immunocompetent and 31 immunosuppressed). ASCUS and LSIL represented respectively 26.8% and 22.0% of the control patients and 28.6% and 39.7% of the Crohn′s patients, with no statistically significant difference between the groups. HPV was identified in 17.1% of patients in the control group and 27% of patients with CD by the molecular method, being predominantly high risk in both groups. In a subanalysis considering Crohn’s disease patients with and without immunosuppression and the control group, there was no statistical difference between the frequencies detected by PCR and hybridisation (p = 0.084) as well as the anal manifestation of Crohn’s disease. The Kappa coefficient for agreement between smear anal cytology and HPV identification by PCR and hybridisation was -0.127 in the total sample. Conclusion In this study, is possible to conclude that in the sample studied there was no difference between subclinical HPV anal infection between control patients and Crohn’s disease group evaluated by both cytology and hybridisation and immunosuppression and anal impairment did not influence these results either. Anal cytology and hybridisation did not show agreement represented by the Kappa coefficient in this population.

Assessment of clinical performance of an ultrasensitive nanowire assay for detecting human papillomavirus DNA in urine

ObjectiveTo evaluate whether HPV DNA in urine has potential advantages as an alternative biomarker for HPV-based cervical cancer screening. MethodsAmong patients with Cobas HPV test results, a total of 67 HPV-positive (n = 42) and -negative (n = 25) women who agreed to participate in this study were willing to provide paired cervical and urine samples, and we observed concordance between sample types from each patient in identifying HPV genotypes using the nanowire assay. ResultsWe detected high-risk strains of HPV DNA in unprocessed urine specimens using polyethyleneimine-conjugated nanowires (PEI-NWs). Concordance for high-risk HPV (hrHPV) between paired urine and cervical samples was 90.4% (κ = 0.90; 95% CI: 0.80–100.00). The virological sensitivity and specificity for detection of HPV DNA from a small urine sample (200 μL) were 81.3% (κ = 0.83; 95% CI: 62.1–100.0) and 98.0% (κ = 0.83; 95% CI: 94.2–100.0) for HPV16 group, 100.0% (κ = 0.65; 95% CI: 100.0–100.0) and 95.3% (κ = 0.65; 95% CI: 90.1–100.0) for HPV18 group, and 96.4% (κ = 0.97; 95% CI: 89.6–100.0) and 100.0% (κ = 0.97; 95% CI: 100.0–100.0) for other hrHPV group, respectively. ConclusionsThe nanowire assay demonstrated excellent ability to identify HPV DNA from urine specimens. We observed an excellent agreement in the detection of high-risk HPV between paired urine and cervical samples, even with small urine sample volume.

Human papillomavirus and human telomerase RNA component gene in cervical cancer progression

This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.