HPV-infected Patients Research Articles

Sexual dysfunction in women with human papilloma virus infection in the Turkish population

Human papilloma virus infection (HPV) is the most common sexually transmitted disease. It may increase the risk of several cancers, including those of the cervix, vulva, vagina, head and neck. HPV is usually transmitted during sexual intercourse; there are limited data about sexual dysfunction (SD) after infection with this virus. We aimed to measure the incidence of SD in women with HPV. In this study, we evaluated 67 HPV-infected female patients and 66 healthy controls. The Arizona Sexual Experience Scale (ASEX), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Socio Demographic Form were used for evaluation. Gynaecologists and psychiatrists evaluated the participants. Women with HPV were found to have significantly higher Arizona Sexual Experience Scale (ASEX) total scores and ASEX sub scores than the control group in the domains of sexual desire, arousal, genital response, orgasmic experience and their satisfaction from orgasm (p ≤ .05). The study group shows a statistically significant difference in the Beck Depression Inventory (BDI), but Beck Anxiety Inventory (BAI) scores show no significant differences between the experimental and control groups. Our study shows that HPV positivity in female patients is associated with a significant impairment in sexual function and that this impairment is not related to depression or anxiety. Impact statement What is already known on this subject? There are only a few studies concerned with sexual dysfunction in HPV patients. These studies have methodological problems, as they do not rule out the effect of depression on sexual dysfunction. It is very difficult to perform studies on sexual dysfunction and sexually transmitted diseases, because both physicians and patients are reluctant to talk about sexual problems. In the present study, only 6 out of 15 physicians accepted to contribute to the study. Although the physicians gave a questionnaire to more than 400 patients, only 133 of them completed that questionnaire. The most important difficulties in this study was to find enough patients. What do the results of this study add? Depression and sexual dysfunction are frequently seen in HPV patients. Although depression is one of the most common causes of sexual dysfunction, an HPV infection may lead to sexual dysfunction even in the patients without depression. What are the implications of these findings for clinical practice and/or further research? HPV infections may be associated with mental health problems and sexual dysfunction. The gynaecologists and other clinicians working with HPV patients should also evaluate patients psychologically and refer patients to psychiatry if required. The psychiatric problems associated with an HPV infection do not only impair sexual functions, but also may lead to difficulties in social life.

The association between human papillomavirus infection and head and neck cancer: A population-based cohort study.

Human papillomavirus (HPV) has been linked with development of oropharyngeal squamous cell carcinoma, a subset of head and neck cancer (HNC). This study aimed to evaluate the association between HPV infection and subsequent development of HNC and to report epidemiological information in Taiwan.This population-based cohort study retrieved patient data from the longitudinal health insurance database (LHID) of Taiwan's National Health Insurance Research Database (NHIRD) from 2005 to 2010 and analyzed it retrospectively. The crude incidence rate and incidence rate ratios with 95% confidence intervals of HNC were estimated in patients with and without HPV infection. A time-to-event analysis was conducted and multiple regression analysis was performed to identify factors associated with HNC in HPV-infected patients, including age at baseline, sex, and comorbidities.This study included the data of 25,520 HPV-infected and 1,061,817 noninfected patients. The HPV-infected group had a significantly higher proportion of females than the noninfected group (55.80% vs 50.66%, respectively; P < .0001). The incidence rate of HNC was 11.49 (males) and 5.83 (females) per 10 person-months versus 11.38 (males) and 3.90 (females) per 10 person-months in the infected and noninfected groups, respectively. HPV was significantly associated with cancer in females (hazard ratio = 1.520, 95% confidence interval 1.166-1.981), but not in males (hazard ratio = 1.000, 95% confidence interval 0.815-1.228). No significant differences were found in age between the HPV-infected and noninfected patients (49.20 ± 14.34 years vs 49.09 ± 13.82 years, respectively); and a slightly higher percentage of HPV-infected patients had a specific comorbidity than did noninfected patients 12.54% versus 9.43%, ischemic heart disease 14.22% versus 10.51%, hypertension 22.40% versus 19.54%, liver disease 22.88% versus 16.17%, and renal disease 7.14% versus 5.39%, respectively.Results of this study may help clinicians in the diagnosis, prognosis, and treatment of head and neck cancer.

Risk of systemic lupus erythematosus in patients with human papillomavirus infection: a population-based retrospective cohort study.

Viral infection contributing to systemic lupus erythematosus (SLE) development has been largely reported. However, the SLE risk in patients with human papillomavirus (HPV) infection is unknown. Data were retrieved from the Longitudinal Health Insurance Database (2000) in Taiwan. We identified 43,567 patients with HPV infection and 174,268 age- and sex-matched uninfected controls from 2002 to 2012. Individuals were followed up from index date (first date of diagnosis with HPV) until the occurrence of SLE, at the end of the study (December 2013), or when they were withdrawn from the insurance program. The incidence rate ratio (IRR) was calculated using the univariate Poisson regression. The adjusted hazard ratios (aHRs) were calculated, and sensitive and subgroups analyses were also conducted. Compared with the non-HPV controls, the IRR of SLE in HPV patients was 1.52 (95% confidence interval (CI): 1.09-2.12). The risk of SLE in HPV-infected individuals was significantly high (aHR: 1.48, 95% CI: 1.06-2.06) after adjusting for age, sex, and comorbidities. Men aged between 16 and 45 years were more susceptible to developing SLE (aHR: 21.57, 95% CI: 2.52-184.60, p = 0.0051). Our study showed a significantly higher risk of SLE among HPV-infected patients, especially in men aged between 16 and 45 years.

Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection.

Infection with human papillomavirus (HPV) is the main cause of cervical cancer. Viral persistence is considered the main risk factor for neoplastic progression and evidence suggests that regulatory T cells (Treg) play an important role in the failure of viral elimination. The aim of this study was to detect phenotypic markers of Treg and cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β, in the cervical microenvironment of HPV-infected patients. One hundred and one samples of uterine cervix embedded in paraffin were analyzed. We used immunohistochemistry to examine the coexpression of the CD25/FOXP3 and CD4/TGF-β markers, and the expression of GITR and IL-10 in cells present in the cervical stroma. We detected a microenvironment composed of high proportions of CD25+ FOXP3+ , CD4+ TGFβ+ , IL-10+ , and GITR+ cells in samples with high viral loads and severe lesions of HPV-infected patients. The abundance of these markers, indicative of the presence of Treg cells and immunosuppressive cytokines, was significantly associated with severe lesions and elevated viral loads in the examined samples. These results suggest that Treg cells may be involved in maintaining a microenvironment favorable for viral persistence and neoplastic progression. Our findings support those of previous studies that suggested that these markers could be used to predict HPV persistence and neoplastic progression, and as potential targets for immune response modulation.

Abstract CT080: Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression

Abstract Introduction : The poly-gamma-glutamic acid (γ-PGA) is a safe and edible polypeptide that is naturally synthesized by Bacillus subtilis 1 and has long been taken up as an ingredient of fermented soybean foods. The γ-PGA as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to enhance natural killer (NK) cell activity and inhibit tumors. Although CIN-1 typically represents transient infection, about 10% of CIN-1 is found to progress to CIN-3, and HPV infection persists and leads to high grade cervical dysplasia in some women with CIN-1. The aim of this study was to investigate the efficacy and safety of γ-PGA and impact γ-PGA on the immune system including PD-1 / PD-L1 in patients with CIN 1. Material &amp; Methods : We conducted a multi-center, randomized, double blind, placebo control, parallel designed, phase 2b study. Participants were randomly assigned to one of two groups: half received oral solution containing 1500 mg of γ-PGA; half received a placebo. Each participants took one dose every 24 hours for 4 weeks. Colposcopy with biopsy was assessed at the time of screening and 12 weeks. Blood samples were drawn at the initial treatment and at the 4th, 8th, 12th weeks after treatment. The primary endpoint of the study was histologic regression rate between screening and 12th weeks. The secondary endpoint were cytologic response rate, HPV clearance, change of immune responses and PD-1/PD-L1 expression. Result From April 2013 to December 2015, 254 patients were screened and a total of 200 patients participated in the study. Of these, Of 101 women in γ-PGA group, 42 (42.4%) women experienced histologic regression, whereas 26 (27.1%) in the control group experienced histologic regression, showing statistically significant differences (p=0.018). In the γ- PGA group, HPV clearance was found in 37 (43.5%) of the 85 high-risk HPV infected patients, showing a meaningful difference compared to the control group showing HPV clearance of 20 (26.7%) out of 75 (p=0.026). However, there was no significant difference between the two groups in terms of cytologic regression rate and type specific clearance of HPV. The immunologic factors including NK cell activity, CD8 cell count and PD-1/PD-L1 expression, which are thought to be related to the therapeutic mechanism of γ- PGA, showed no significant difference between the two groups. Conclusion : The γ-PGA enhance histologic regression in CIN-1 patients and showed the possibility of non-invasive medical treatment. In addition, γ-PGA has shown its potential as a treatment for high-grade CIN or cancer in the future as it has been shown to be effective against high-risk HPV infection. Citation Format: Hyun-Woong Cho, Yung-Taek Ouh, Jin Hwa Hong, Jae Kwan Lee, Jae-Won Jeon, Moon-Hee Sung. Clinical and immunologic results of a multi-center, randomized, double blind, phase II trial using poly-gamma-glutamic acid (γ-PGA) for women with cervical intraepithelial neoplasia 1 (CIN 1) and correlation of PD-1/PD-L1 tumor expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT080.

The Correlation of the MicroRNA129-2 and SOX4 Genes Expression in HPV-infected Cervical Cancer Patients

The Correlation of the MicroRNA129-2 and SOX4 Genes Expression in HPV-infected Cervical Cancer Patients

Effectiveness of Photodynamic Therapy in Elimination of HPV-16 and HPV-18 Associated with CIN I in Mexican Women.

This study aimed to determine the effectiveness of photodynamic therapy (PDT), using δ-aminolevulinic acid (5-ALA), in the elimination of premalignant cervical lesions in Mexican patients with human papillomavirus (HPV) infection and/or cervical intraepithelial neoplasia (CIN). Thirty women diagnosed with CIN I and/or positive for HPV participated in the study. Topical 6% 5-ALA in gel form was applied to the uterine cervix; after 4 h, the lesion area was irradiated with a light dose of 200 J cm-2 at 635 nm. This procedure was performed three times at 48-h intervals. Clinical follow-up was performed at 3, 6, and 12 months after the initial PDT administration, by colposcopy, cervical cytology, histopathological analysis, polymerase chain reaction, and hybrid capture. Of HPV-infected patients without evidence of CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although this response was not statistically significant. PDT using 6% 5-ALA is concluded to be effective in eliminating HPV infection associated or not with CIN I.

IL-10 gene polymorphism c.-592C > A increases HPV infection susceptibility and influences IL-10 levels in HPV infected women

Interleukin-10 (IL-10) influences HPV infection and viral persistence, favoring cervical immunosuppression and cervical carcinogenesis. IL-10 levels may be influenced by HPV itself and by IL-10 polymorphisms, including rs1800872 (c.-592C>A). Therefore, we evaluated the influence of IL-10 c.-592C>A polymorphism in HPV infection and in IL-10 plasmatic/cervical levels in HPV infected and non-infected women. The study included 174 infected and 186 non-infected patients. Cervical epithelial scrapings were obtained to determine HPV DNA presence PCR. Peripheral blood samples were obtained to determine IL-10 polymorphism by PCR-RFLP, while IL-10 levels were assessed by ELISA. HPV was more prevalent among allele A carriers (p<0.001), with IL-10 c.-592C>A polymorphism being associated with HPV infection. As demonstrated by binary logistic regression analysis, heterozygotes [ORadj=2.081 95% CI (1.222–3.544), p=0.007] and homozygotes [ORadj=3.745 95% CI (1.695–8.271), p=0.001] showed approximately 2 and 4 time's greater odds, respectively, of presenting HPV when compared to CC patients. Moreover, HPV infected patients carrying polymorphic allele A showed higher IL-10 cervical levels (p=0.039). Binary logistic regression analysis demonstrated that IL-10 cervical levels were not independently associated to CA+AA genotypes (p=0.162), neither to HPV's presence (p=0.061), thus IL-10 cervical levels are possibly increased because of both HPV and allele A presence. Taken together, these findings suggest that IL-10 c.-592C>A polymorphism is independently associated with HPV infection susceptibility exerting influence on IL-10 cervical levels in HPV infected women, thus contributing to cervical carcinogenesis.

Human papillomavirus, Epstein-Barr virus, and methylation status of p16ink4a in penile cancer.

Little is known about penile carcinogenesis. The aim of this study was to evaluate the prevalence of HPV and EBV, and the methylation status of p16ink4a in penile cancer samples, and to contribute to the understanding of the mechanisms responsible for penile cancer development. HPV DNA was detected in 63.6% of 122 cases, with HPV16 being the most prevalent type. EBV DNA was detected in 47.7%, with EBV-1 being the most prevalent type. HPV/EBV co-infections were found in 27.3% of the cases. Hypermethylation in p16ink4a was detected in 64.5% of 110 tested cases. An association between the absence of HPV absence and p16ink4a hypermethylation was also found. Death and/or progressive disease was associated with grade (P = 0.001), T stage (P < 0.0001), and N stage (P < 0.0001). In the multivariable model, grade and N stage were independent risk factors for disease-free survival (P = 0.008 and P < 0.001, respectively). Patients without viral infection had a median age significantly lower than that of the HPV-infected patients. We suggest at least two pathways for penile carcinogenesis, one HPV-independent linked to epigenetic events, probably via p16ink4a inactivation; and another, dependent on HPV infection.

Genotype-specific methylation of HPV in cervical intraepithelial neoplasia.

ObjectiveHypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings.MethodsCervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR).ResultsThe degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2.ConclusionOur study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.

Relationship of HPV infection and BV, VVC, TV: a clinical study based on 1 261 cases of gynecologic outpatients

Objective: To Explore the relationship between HPV infection and bacterial vaginosis(BV), vulvovaginal candidiasis(VVC), and trichomonal vaginitis(TV). Methods: Clinical data from 1 261 gynecologic outpatients who underwent the vaginal microecology and HPV type detection during June 2015 to December 2015 were collected and analyzed in the First Affiliated Hospital of Xi'an Jiaotong University. Results: In 1 261 patients, 328 cases infected with HPV, infection rate was 26.01%(328/1 261); vaginal infectious disease in 328 cases of HPV infections were 219 cases(66.8%, 219/328), vaginal infectious diseases in 933 cases of HPV uninfected were 503 cases(53.9%, 503/933), incidence of vaginal infectious disease in HPV infected patients was higher than that in HPV uninfected patients(χ2=5.87, P=0.01). 142 cases of BV had 54 cases infected with HPV(38.0%, 54/142), 296 cases of intermediate type BV had 88 cases infected with HPV(29.7%, 88/296), 231 cases of normal vaginal microecology had 51 cases infected with HPV(22.1%, 51/231), 99 cases of VVC had 15 cases infected with HPV(15.2%, 15/99), 2 patients with TV had 0 cases infected with HPV(0/2), HPV infection rate in BV, intermediate type BV patients were significantly higher than normal patients(P<0.05), while there were no statistical differences among VVC, TV and normal patients(P>0.05). The intensity of HPV infection were positively correlated with BV, intermediate type BV(OR=2.17, 95% CI: 1.37-3.43, P<0.01; OR=1.49, 95% CI: 1.00-2.22, P= 0.04); while, VVC, TV were uncorrelated with HPV infection(all P>0.05). Conclusions: BV, intermediate type BV are positively correlated with HPV infection, especially for the high-risk HPV. VVC and TV are not correlated with HPV infection.

Punch biopsy guided by both colposcopy and HR-HPV status is more efficient for identification of immediate high-grade squamous intraepithelial lesion or worse among HPV-infected women with atypical squamous cells of undetermined significance

ObjectivesTo investigate the accuracy of colposcopy for diagnosing high-grade squamous intraepithelial lesion (HSIL) or worse (HSIL+) in human papillomavirus (HPV)-infected patients with atypical squamous cells of undetermined significance (ASCUS) cytology, and determine whether genotyping and viral load quantitation can be useful for detecting immediate HSIL+ risk in these patients. Study designThis study included 620 cases with ASCUS and positive for high-risk (HR)-HPV within 1 month before or after cervical cytology at Qilu Hospital between February 2013 and February 2014. Based on the colposcopic impression, lesion-targeted punch biopsy, endocervical curettage biopsy or random cervical punch biopsy in four quadrants was performed on these patients within 1 month. The accuracy of colposcopy for diagnosing HSIL+ was evaluated through comparison with the biopsy results. HR-HPV status determined by Hybrid Capture 2 or HPV genotyping was analysed retrospectively as a possible predictor of HSIL+. ResultsAgreement between colposcopic impression and cervical pathology was matched perfectly in 89.2% of cases (553/620), and the strength of agreement with the κ statistic was 0.698 (p<0.001). Colposcopy had high specificity (96.9%) but low sensitivity for detecting HSIL+ (67.5%). The risk of HSIL+ was significantly higher in patients with HPV-16 infection (52.3%) than in patients infected with other types of HPV (17.9%, p<0.001). HSIL+ and virus load was correlated at cut-offs (CO) of 50 relative light units (RLU)/CO and 100 RLU/CO (p=0.024 and 0.044, respectively). If considering HPV16 infection or high virus load (at 50 RLU/CO) as a diagnostic standard of HSIL+ when colposcopic impression was negative, sensitivity was improved to 74.7% and 81.0%, respectively. ConclusionsGood agreement was found between colposcopic and pathologic diagnosis. HR-HPV genotyping or virus load is relevant to the detection of HSIL+ among HPV-infected patients with ASCUS cytology. In these patients, biopsies considering HPV-16 infection or virus load ≥50 RLU/CO may be helpful for increasing the HSIL+ detection rate.

MiRNA Expression Profiles of HPV-Infected Patients with Cervical Cancer in the Uyghur Population in China

The study aimed to investigate the state of human papillomavirus (HPV) infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA) microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30), and the main subtype identified was HPV16 (29 of 29). HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29). Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.

Interleukin 10 promotes immune response by increasing the survival of activated CD8+ T cells in human papillomavirus 16-infected cervical cancer.

Human papillomavirus (HPV)-specific CD8+ T cells are present in HPV-infected cervical cancer patients and have demonstrated potent antitumor properties. However, these cells cannot control tumor progression in most patients. To investigate the underlying mechanisms involved in suppressing or promoting CD8+ T cell functions, we focused on interleukin 10 (IL-10), a pleiotropic cytokine with controversial roles in antitumor immunity. We found that compared to healthy controls, circulating CD8+ T cells in HPV 16-infected cervical cancer patients expressed significantly higher levels of IL-10. Interestingly, these CD8+ T cells from cervical cancer patients, but not those from healthy controls, responded to HPV 16 E6/E7 peptide stimulation by increasing IL-10 expression, demonstrating an antigen-specific IL-10 release. Addition of exogenous IL-10 improved the survival, but did not increase the proliferation, of peptide-stimulated CD8+ T cells. CD8+ T cells cultured in the presence of IL-10 also resulted in significantly higher interferon gamma (IFN-gamma) and granzyme B concentration, primarily due to improved cell survival. In resected cervical tumors, the frequency of tumor-infiltrating IL-10+ CD8+ T cells was positively correlated with the frequency of tumor-infiltrating IFN-gamma+ and granzyme B+ CD8+ T cells. Tumor-associated macrophages were more potent than peripheral blood monocyte-derived macrophages at inducing IL-10 expression in CD8+ T cells, possibly explaining the elevated IL-10+ CD8+ T cell frequency in cervical cancer patients. Together, these results are consistent with an immunostimulatory role of IL-10, which promoted CD8+ T cell response by increasing the survival of activated CD8+ T cells.

Reduction of microRNA-184 by E6 oncoprotein confers cisplatin resistance in lung cancer via increasing Bcl-2.

MicroRNA-184 suppresses cell growth and survival via targeting c-Myc and Bcl- 2. We recently reported that miR-184 promotes tumor progression in non-small cell lung cancer via targeting CDC25A and c-Myc. We here hypothesized that miR-184 could be down-regulated by E6 oncoprotein to confer cisplatin resistance in NSCLC. Human papillomavirus (HPV) 16-positive lung cancer TL-1 and cervical cancer SiHa cells compared with HPV16-negative TL-10 and C33A cells were enrolled for E6 manipulation. MiR-184 expression levels were increased by E6-knockdown in TL-1 and SiHa cells, but decreased by E6-overexpression in TL-10 and C33A cells. The MTT assay showed that the inhibition concentration of cisplatin yielding for 50% cell viability was dependent on miR-184 levels. Bcl-2 de-targeted by E6-mediated miR- 184 reduction was responsible for cisplatin resistance. Luciferase reporter assay and real- time PCR analysis indicated that the miR-184 promoter activity and its expression were modulated by E6 and/or p53 manipulation. Chromatin immunoprecipitation (ChIP) assay confirmed that p53 was bound onto the miR-184 promoter and its binding activity was modulated by E6 and/or p53 manipulation. Among patients, high miR184 and high Bcl-2 mRNA expression was more commonly occurred in E6- positive tumors than in E6-negative tumors. Fifty-nine out of 136 patients receiving cisplatin-based chemotherapy were available for the retrospective study. Patients with low-mR-184, E6-positive, high-Bcl-2 tumors, and both combinations were more prevalently occurred unfavorable response to cisplatin-based chemotherapy than their counterparts. In conclusion, a decrease in miR-184 level by E6 oncoprotein may predict unfavorable response to cisplatin-based chemotherapy in HPV-infected NSCLC patients via increasing Bcl-2 expression.

Human Papilloma Virus Infection in Patients with Male Accessory Gland Infection: Usefulness of the Ultrasound Evaluation.

This study evaluated the ultrasound (US) features of 20 patients with MAGI and concomitant papilloma virus (HPV) infection compared to 20 patients with microbial (presence of Chlamydia trachomatis alone) MAGI and 20 patients with amicrobial (inflammatory) MAGI. Patients with HPV infection showed significantly (p < 0.05) higher total prostate, seminal vesicles, and epididymal US signs (18.0 ± 2.0) compared to the other 2 groups (12.0 ± 4.0 versus 10.0 ± 3.0, resp.). In addition, patients with MAGI and HPV had a higher prevalence of complicated forms of MAGI [prostatovesiculitis (PV) and prostate-vesiculo-epididymitis (PVE)] and a higher frequency of the fibrosclerotic variant compared to the other groups (70.0 ± 10.0% versus 48.0 ± 5.0% versus 15.0 ± 10.0%). Moreover, HPV infected patients had a higher number of US criteria suggestive for MAGI in the periurethral region of the prostate compared to the other groups. In particular, the patients showed a higher ratio between periurethral and lobar US criteria distribution (5.0 versus 0.5). Finally, the seminal fluid concentration of CD45pos leukocytes (2.0 ± 0.2 versus 1.3 ± 0.3 versus 1.0 ± 0.3 mil/mL) was significantly higher and sperm progressive motility was significantly lower in these patients compared to other groups.

Detection of Human Papillomavirus 16-Specific IgG and IgM Antibodies in Patient Sera: A Potential Indicator of Oral Squamous Cell Carcinoma Risk Factor.

The association between human papillomavirus type 16 (HPV16) and oral cancer has been widely reported. However, detecting anti-HPV antibodies in patient sera to determine risk for oral squamous cell carcinoma (OSCC) has not been well studied. In the present investigation, a total of 206 OSCC serum samples from the Malaysian Oral Cancer Database & Tissue Bank System, with 134 control serum samples, were analyzed by enzyme-linked immunosorbant assay (ELISA) to detect HPV16-specific IgG and IgM antibodies. In addition, nested PCR analysis using comprehensive consensus primers (PGMY09/11 and GP5+/6+) was used to confirm the presence of HPV. Furthermore, we have evaluated the association of various additional causal factors (e.g., smoking, alcohol consumption, and betel quid chewing) in HPV-infected OSCC patients. Statistical analysis of the Malaysian population indicated that OSCC was more prevalent in female Indian patients that practices betel quid chewing. ELISA revealed that HPV16 IgG, which demonstrates past exposure, could be detected in 197 (95.6%) OSCC patients and HPV16-specific IgM was found in a total of 42 (20.4%) OSCC patients, indicating current exposure. Taken together, our study suggest that HPV infection may play a significant role in OSCC (OR: 13.6; 95% CI: 3.89-47.51) and HPV16-specific IgG and IgM antibodies could represent a significant indicator of risk factors in OSCC patients.

Prevalence of microorganisms co-infections in human papillomaviruses infected women in Northern China

Due to scarce data on the prevalence of genital microorganism infections among individuals with human papillomavirus (HPV) infections, the present study aimed to evaluate microorganism co-infections and associated risk factors in HPV-infected women in Northern China. Cervical samples of 4290 enrolled female patients were collected to detect HPV, bacterial and yeast infections in gynecologic outpatients. Serum samples collected were analyzed for the presence of serological markers for human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) and Treponema pallidum infections. HPV typing was carried out by polymerase chain reaction and flow-through hybridization on cervical brush specimens. Chlamydia trachomatis was identified by strand displacement amplification, and other microorganisms were detected by conventional methods. Odds ratio of co-infection was assessed between HPV-positive and -negative patients. Overall, co-infections among HPV-infected patients showed a trend for risk compared with HPV-negative patients. In this cross-sectional study on 4290 female outpatients, statistical analyses revealed a significant association between HPV and detection of anti-HBV antibodies, bacterial vaginosis, C. trachomatis and Ureaplasma urealyticum; no correlation was found between HPV infection and anti-HIV, anti-HCV, T. pallidum, Trichomonas vaginalis and Neisseria gonorrhoeae, which were detected only in few cases among either HPV-positive or -negative patients. The study demonstrated a significant association between HPV and HBV, bacterial vaginosis, C. trachomatis and U. urealyticum. The study results suggest that it may be important to screen for the simultaneous presence of different microorganism co-infections with HPV that may have synergistic pathological effects.

Examining IL-33 expression in the cervix of HPV-infected patients: a preliminary study comparing IL-33 levels in different stages of disease and analyzing its potential association with IFN-γ.

Research has shown the essential role of interleukin-33 (IL-33) in driving protective anti-viral immunity. IFN-γ has been reported to improve IL-33 expression in cultured epithelial cells. The development of cervical intraepithelial neoplasia (CIN) and carcinogenesis was closely related to human papilloma virus (HPV) infection and defective anti-viral immunity. The aim of this study was to investigate IL-33 expression alternation during the disease progress and its association with IFN-γ in HPV-positive patients. IL-33 was detected in endothelial cells and populations of epithelial cells in cervix. Though there was no statistically significant difference of IL-33 levels in cervical lavage and serum among different stages of disease (P > 0.05), the IL-33 protein and mRNA levels in cervical tissues were significantly lower in severe CIN patients than that of mild CIN or no CIN patients (P < 0.05). In addition, IL-33 protein levels were positively correlated with IFN-γ mRNA levels in all groups except cervical cancer (CA) group (r = 0.546, P < 0.01). In vitro, IFN-γ was also found to upregulate IL-33 expression in human epidermal keratinocytes (NHEKs) in a dose-dependent manner. However, CA tissues did not show further reduced IL-33 protein and mRNA levels compared with severe CIN tissues (P > 0.05). IFN-γ mRNA levels were even higher in CA tissues than in severe CIN tissues (P < 0.05). Therefore, in cervical precancerous tissues, IL-33 levels were lower in more severe lesions and that may be related to diminished local IFN-γ.

Paxillin promotes tumor progression and predicts survival and relapse in oral cavity squamous cell carcinoma by microRNA-218 targeting.

High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the molecular pathogenesis of HPV-infected OCSCC remains unclear. Paxillin (PXN) has been reported to promote lung tumor progression by miR-218 targeting. In addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in cervical cancer. We thus asked whether PXN can promote tumor progression by E6-reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies demonstrated that PXN expression increased markedly upon E6-mediated reductions in miR-218, resulting in increased colony formation and invasion capabilities in HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was negatively associated with miR-218 expression and positively associated with PXN expression. Kaplan-Meier and Cox regression models demonstrated that patients with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low-PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN tumors and both combinations exhibited the worst OS and RFS compared with patients in their counterparts. These observations in patients were consistent with the findings from the cell model. Therefore, we suggest that PXN might be targeted to suppress tumor progression and consequently to improve outcomes in OCSCC, especially in HPV-infected OCSCC.