Single Human Papillomavirus Type Research Articles

Prevalence characteristics of cervical human papillomavirus infection in Chengdu and Aba District, Sichuan Province, China.

The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs. A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women's and Children's Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real-time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed. The overall HPV prevalence was 22.51% in Chengdu. During 2015-2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions. Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China.

HPV prevalence and genotype distribution in 2,306 patients with cervical squamous cell carcinoma in central and eastern China.

To explore the positivity rate and genotype distribution of human papillomavirus (HPV) in cervical squamous cell carcinoma (CSCC) tissues in central and eastern China and to provide theoretical basis for cervical cancer screening and prophylactic HPV vaccine development in China. DNA was extracted from paraffin-embedded tissues of CSCC samples and exfoliated cervical cells of cervical cancer screening populations. 23 HPV genotypes were detected by combining polymerase chain reaction (PCR) and reverse dot hybridized gene chip detection technology in 2,306 CSCC tissues and 10,245 cervical cancer screening populations. The genotype distribution of HPV infection was analyzed. The overall infection rate of HPVs in 2,306 CSCC patients was 92.71%. The frequency of single-type HPV infection and multiple-type HPV infection were 86.48% and 13.51%, respectively. The most common HPV genotypes detected in Chinese CSCC tissues were HPV-16, HPV-18, HPV-31, HPV-33, HPV-45, HPV-52, HPV-58, and HPV-59. The overall positivity rate of these eight high-risk HPV (HR-HPV) genotypes in HPV-positive CSCC was as high as 96.91%. Of which the positivity rate of seven HR-HPV genotypes related to nine-valent HPV vaccines in HPV-positive CSCC was 95.09%. Meanwhile, the overall infection rates of HR-HPV and low-risk HPV (LR-HPV) in female aged 35-64 years who underwent cervical cancer screening were 13.16% and 1.32%, respectively. The high-frequency HR-HPV genotypes in cervical cancer screening women were HPV-52, HPV-58, HPV-16, HPV-53, HPV-68, HPV-39, HPV-51, and HPV-56, with positivity rates of 2.25%, 1.60%, 1.31%, 1.22%, 0.93%, 0.92%, 0.78%, and 0.74%, respectively. Among women screened for cervical cancer in China, detecting the 8 high-frequency HR-HPV genotypes can reduce technical difficulty and reagent costs, while also improving the efficiency and effectiveness of cervical cancer screening. HPV genotyping assists gynecologists in assessing the risk of HR-HPV-positive cervical intraepithelial neoplasia and guiding them in implementing appropriate interventions. Furthermore, HPV genotyping is helpful for doctors to follow up HR-HPV-positive women and to evaluate the protective effect of HPV vaccine.

Pattern of infection and genotypes of human papillomavirus in Zhengzhou City based on a four–year (2015-2018) epidemiological study

ABSTRACT Persistent human papillomavirus (HPV) infection has been associated with the development of cervical cancer. To reduce the incidence of cervical cancer and promote awareness of HPV, a government-sponsored epidemiological study was conducted from 2015 to 2018 in Zhengzhou City. A total of 184,092 women aged 25–64 years were included, of which 19,579 were infected with HPV, reflecting a prevalence of 10.64 percent (19,579/184,092). The HPV genotypes found were classified as high-risk (13 genotypes) and low-risk (8 genotypes). Single and multiple infections were detected in 13,787 (70.42 percent) and 5,792 (29.58 percent) women, respectively. The five most common high-risk genotypes detected, listed in descending order, were HPV52 (2.14 percent; 3,931/184,092), HPV16 (2.04 percent; 3,756/184,092), HPV58 (1.42 percent; 2,607/184,092), HPV56 (1.01 percent; 1,858/184,092), and HPV39 (0.81 percent; 1,491/184,092). Meanwhile, the most common low-risk genotype was HPV53 (0.88 percent; 1,625/184,092). The prevalence of HPV gradually increased with age, with the highest occurring in women aged 55–64 years. The prevalence of single-type HPV infection decreased with age, whereas that of multiple-type HPV infection increased with age. This study indicates a high burden of HPV infection in women in Zhengzhou City.

Application of multiplex PCR capillary electrophoresis and analysis of distribution characteristics of HPV infection subtypes

Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ2=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ2=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.

The prevalence of human papillomavirus among women in northern Guangdong Province of China

Globally, cervical cancer, whose etiologic factor is Human papillomavirus (HPV), is the third most common cancer among women. In cervical cancer screening, HPV testing is important. However, the prevalence of HPV in northern Guangdong Province has not been conclusively determined. A total of 100,994 women attending Yuebei People's Hospital Affiliated to Shantou University Medical College between 2012 and 2020 were recruited. HPV was tested by a polymerase chain reaction (PCR)-based hybridization gene chip assay. The prevalence of HPV among these women was established to be19.04%. Peak prevalence was observed in women aged 40–49 (7.29%). Besides, the prevalence of single-type HPV infection (14.46%) was significantly high, compared to multiple-type infection (4.58%) (p < 0.01), while the prevalence of high-risk HPV infection (19.97%) was significantly higher than that of low-risk genotypes (5.48%) (p < 0.01). The most prevalent high-risk genotypes were HPV52 (4.16%), HPV16 (2.98%), HPV58 (2.15%), HPV53 (1.58%) and HPV68 (1.34%). HPV co-infection with up to 10 genotypes was reported for the first time. Our findings suggested a high burden of HPV infections among women in northern Guangdong. Establishing the prevalence and genotype distribution characteristics of HPV infections in the region can contribute to cervical cancer prevention through HPV vaccination.

HPV and HIV Coinfection in Women from a Southeast Region of Romania-PICOPIV Study.

Background and Objectives: Romania faces one of the highest cervical cancer burdens in Europe though it is a preventable cancer through population screening by cytology and human papillomavirus (HPV) detection. Also, it has one of the highest incidences of human immunodeficiency virus (HIV) infection. HPV and HIV coinfection are frequently encountered. The aim of study was to establish the prevalence of HPV infection among HIV-positive women in Southeast Region of Romania, to genotype high risk HPV types -and to correlate the results with clinical data and cytological cervical lesions. Materials and Methods: 40 HIV-positive women were screened for HPV types and for cytological cervical lesions. The findings were evaluated in correlation with CD4 cell counts, HIV viral load, age at first sexual intercourse, number of sexual partners, vaginal candidiasis, and Gardnerella using statistical methods. Results: 19/40 (47.5%) women were positive for HPV types, 63.15% infected with single HPV type and 36.85% with multiple HPV types. The most frequent types were type: 31 (42.1%), 56 (31.57%), 53 (15.78%). On cytology, 34 (85%) women were found with NILM of which 38.23% were HPV-positive. Fifteen percent of women had abnormal cytology (three ASC-US, three LSIL), and all of them were HPV-positive. Through analyzing the value of CD4 count, women with CD4 count ≤ 200 cells/μL were found to be significantly more likely to be infected with HPV; meanwhile there was no correlation between the detection of HPV types and HIV viral load. Candida or Gardnerella were more often associated with HIV-positive women with HPV, than in women without HPV. Conclusions: Infection with HPV types is common among HIV-positive women in the Southeast Region of Romania and it is associated with age at the beginning of sexual life, number of sexual partners, CD4 value, vaginal candidiasis, and Gardnerella infection.

Determination of human papillomavirus type in archival tissue specimens of invasive cervical cancer using molecular mapping and E6/E7-based polymerase chain reaction.

In our previous study, an L1-based human papillomavirus (HPV) test using liquid-based cytology revealed that some invasive cervical cancers (ICC) exhibited multiple HPV types or harbored no HPV DNA. Here, molecular mapping of formalin-fixed paraffin-embedded cancer tissue specimens from the same patients were conducted to confirm these observations. Among 377 ICC cases, 73 eligible specimens (9 positive for multiple HPV types, 16 negative for HPV, and 48 positive for a single HPV type from the previous study) were reexamined by manual microdissection of cancer lesions, then subjected to HPV genotyping using the uniplex E6/E7 polymerase-chain-reaction method to detect all high-risk and potentially high-risk HPV types. The HPV typing results were confirmed in 52 of 73 cancer cases; among the 21 remaining cases, 15 were discordant and 6 were partially concordant. In total, 8 of 16 (50%) HPV-negative samples became positive; 6 were positive for HPV16 and 2 were positive for HPV67. Moreover, two samples previously positive for HPV6 and HPV53 were negative for HPV. All nine cancers with multiple HPV types were found to harbor only a single HPV type. In total, 63 cancer tissues exhibited a single HPV type. HPV16 and HPV18 were detected in squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Alpha-5 (HPV82), -6 (HPV56), and -9 (HPV31/52/67) HPV types were detected in SCC, whereas Alpha-7 (HPV59/68) types were detected in ADC and adenosquamous carcinoma (ADSCC). These findings suggested that the different HPV types induced different histological cancers. Furthermore, all SCCs and 10 of 11 usual-type ADCs were positive for high-risk HPV types, supporting the use of HPV screening for the detection of these cancers and associated premalignant lesions. HPV16 is likely to remain undetected in some cervical cancer tissues because of low viral-copy-numbers. Putative high-risk HPV types (e.g., HPV67 and HPV82) might be high risk in Japan.

The clinical utility of extended high-risk HPV genotyping in risk-stratifying women with L-SIL cytology: A retrospective study of 8726 cases.

The value of extended high-risk human papillomavirus (hrHPV) genotyping for cervical cancer screening in women with low-grade squamous intraepithelial lesion (L-SIL) cytology has been recognized, but few studies have investigated this. Women with L-SIL Papanicolaou results who underwent human papillomavirus (HPV) genotyping between October 2017 and October 2021 at the Obstetrics and Gynecology Hospital of Fudan University were identified. Their HPV results were correlated with immediate histopathologic follow-up findings. In total, 8726 women who had L-SIL cytology and extended HPV genotyping results were analyzed. The overall hrHPV-positive rate was 84% in women with L-SIL, and the most prevalent hrHPV genotypes were type 52 (HPV52) (20.7%), HPV53 (15.7%), and HPV16 (14.3%). Single and multiple coinfections of hrHPV genotypes were detected in 57.2% and 42.8% of women with positive hrHPV results, respectively. Cervical intraepithelial neoplasia grade ≥2 (CIN2+) was identified in 8.5% of hrHPV-positive women. The CIN2+ detection rate in women who had multiple hrHPV infections (9.9%) was significantly higher than the rate in those who had infection with a single HPV type (7.2%). The top 5 CIN2+-associated HPV infections were HPV16 (25.2%), HPV82 (17.8%), HPV33 (16.3%), HPV31 (14.6%), and HPV26 (13.8%). For the composite group with HPV types HPV16, HPV26, HPV82, HPV31, HPV18, HPV33, HPV58, HPV35, HPV52, and HPV51, the risk of CIN2+ was 11.5% and represented 97.1% of all CIN2+ in biopsied, hrHPV-positive patients. The composite group of 8 remaining HPV genotypes (HPV39, HPV45, HPV53, HPV56, HPV59, HPV66, HPV68, and HPV73) was identified in 29.7% of hrHPV-positive patients, and the risk of CIN2+ for this composite group was similar to the risk of CIN2+ in hrHPV-negative patients. This large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype-specific risk stratification in women with L-SIL.

Prevalence and Genotypes of Human Papillomavirus among Men in Yunnan Province, China.

Human papillomavirus (HPV) infection is one of the most commonly reported sexually transmitted infections. Persistent infection is associated with the development of cervical cancer. Men may serve as a medium for HPV transmission among women, and much remains unknown about the prevalence and genotypes of HPV infection among men in Yunnan Province. This study was designed to investigate these parameters among men in this region. Clinical information was collected from January 2015 to May 2020, and 369 men who wished to undergo tests for HPV were included in this study. HPV screening was performed using the HPV GenoArray Test Kit, and the anatomical site of sample collection was the urethra. The mean age was 36.15 ± 9.08 years. Our results revealed that the prevalence of HPV infection among men was 23.85% in Yunnan Province, and there was no association between age and HPV prevalence in men. There were 72 (81.81%) individuals positive for a single HPV type, and 16 (18.19%) positive for multiple HPV types. The most prevalent oncogenic HPV types were found to be 52, 51, and 16. The most prevalent types of HPV infection were similar between men and women in this region, though the prevalence of HPV in men was relatively high.

Determination of Causative Human Papillomavirus Type in Tissue Specimens of Common Warts Based on Estimated Viral Loads.

Background: Assessment of human papillomavirus (HPV) type-specific viral load (VL) is a valid tool for determining the etiology of HPV-related skin tumors, especially when more than one HPV type is detected within one lesion.Methods: The causative HPV type was determined in 185 fresh-frozen tissue specimens of histologically confirmed common warts (CWs) collected from 121 immunocompetent patients. All tissues were tested using the type-specific quantitative real-time polymerase chain reactions (PCR) for the most common wart-associated Alpha-PV (HPV2/27/57) and Mu-PV types (HPV1/63/204). The presence of 23 additional low-risk HPVs was evaluated using a conventional wide-spectrum PCR.Results: HPV DNA was detected in 176/185 (95.1%) CWs and multiple HPV types in 71/185 (38.4%) lesions. Using the VL approach and a robust cutoff of one viral copy/cell established in this study, HPV2/27/57 were determined as causative agents in 41/53 (77.3%) and 53/71 (74.7%) CWs with single and multiple HPVs, respectively.Conclusions: CWs are mostly etiologically associated with HPV2/27/57 and only rarely with HPV1. In the majority of CWs containing multiple HPVs, a single HPV type was present in high concentration, indicating etiological association. No significant differences in VLs of lesion-causing HPV types in CWs containing single or multiple HPVs were found.

Prognostic implications of genotyping and p16 immunostaining in HPV-positive tumors of the uterine cervix.

Human papillomaviruses (HPVs) are the causative agents of carcinoma of the uterine cervix. A number of HPV genotypes have been associated with cervical cancer and almost all tumors associated with HPV show strong p16 expression. However, there is little information on the possible impact of the HPV genotype and p16 immunostaining on the clinicopathological features or their prognostic value in cervical carcinoma. We evaluated a series of 194 patients with HPV-positive cervical cancers treated at our institution, focusing on the clinicopathological features and the relationship of the HPV genotypes and p16 immunostaining with the prognosis. A single HPV type was identified in 149 (77%) tumors, multiple HPV infection was detected in 30 cases (15%), and undetermined HPV type/s were identified in 15 (8%) carcinomas. HPV 16 and/or 18 were detected in 156 (80%) tumors. p16 was positive in 186 (96%) carcinomas, but eight tumors (4%) were negative for p16 (seven squamous cell carcinomas, one adenocarcinoma); 5/8 caused by HPV 16 and/or 18. Patients with HPV 16 and/or 18 were younger (49 ± 15 vs. 57 ± 17 years, p < 0.01) and more frequently had nonsquamous tumors than patients with other HPV types (24% [37/156] vs. 0% [0/38]; p = 0.01). Neither the HPV type nor multiple infection showed any prognostic impact. Patients with p16-negative tumors showed a significantly worse overall survival than women with p16-positive carcinomas (45 vs. 156 months, p = 0.03), although no significant differences in disease-free survival were observed. In the multivariate analysis, negative p16 immunostaining was associated with a worse overall survival together with advanced FIGO stage and lymph node metastases. In conclusion, the HPV genotype has limited clinical utility and does not seem to have prognostic value in cervical cancer. In contrast, a negative p16 result in patients with HPV-positive tumors is a prognostic marker associated with a poor overall survival.

Characterization of Human Papillomavirus prevalence and risk factors to guide cervical cancer screening in the North Tongu District, Ghana

IntroductionThis population-based study aimed to fill the knowledge gap on Human Papillomavirus (HPV) prevalence and associated sociodemographic risk factors of the general population in the North Tongu District, Ghana. These results are needed to guide cervical cancer prevention efforts, as the leading type of female cancers.MethodsA cross-sectional study including 2002 women in the North Tongu District, Ghana investigated HPV prevalence and associated sociodemographic risk factors. Women were recruited by geographical distribution through the local community-based health system and samples collected using a self-sampling device. For HPV genotyping BSGP5+/6+-PCR with Luminex-MPG readout was used. Multivariate logistic regression analyzed sociodemographic risk factors for HPV positivity.ResultsOf 2002 self-collected samples, 1943 were eligible, contained sufficient DNA and provided valid HPV genotyping results. Prevalence of single high risk HPV types was 32.3% and of multiple high risk types 9.7%. The five most common detected HPV types were HPV16 (7.4%; 95%CI: 6.3–8.7), HPV52 (7.2%; 95%CI: 6.1–8.5), HPV35 (4.8%; 95%CI: 3.9–5.8), HPV59 (4.7%; 95%CI: 3.8–5.8), HPV56 (3.9%; 95%CI: 3.1–4.8). Highest prevalence was observed among women aged 18–24 years, while age 25–54 years was inversely associated with high risk HPV positivity in multivariate analysis. Sociodemographic risk factors identified were i) having any sexual partner, ii) more partners increased the odds for high risk HPV positivity, iii) independently from this marital status, in particular not being married.Discussion & conclusionMost importantly, the high risk HPV prevalence detected from this study is higher than estimates reported for Western Africa. This needs be considered, when deciding on the cervical cancer screening algorithms introduced on a wider scale. Follow-up and triage, depending on the methods chosen, can easily overburden the health system. Self-sampling worked well and provided adequate samples for HPV-based screening. Women with increasing number of sexual partners and not being married were found to have higher odds of being high risk HPV positive, therefore could be a higher prioritized screening target group.

Prevalence of human papillomavirus infection of 65,613 women in East China

BackgroundThe infection with human papillomavirus (HPV) is the major cause of genital disease. This study assessed the prevalence and genotype of HPV among outpatient women and healthy women in Jiangsu, East China.MethodsA total of 65,613 women aged 16–85 years were recruited from Nanjing Kingmed Diagnostics, including 45,736 outpatients and 19,877 healthy women. The cervico-vaginal cells were collected and then HPV types were detected using the Tellgenplex™ HPV DNA Test.ResultsThe overall HPV prevalence was 17.7% for outpatients and 10.6% for healthy women. 13.7% outpatients were infected with a single HPV type and 4.0% were infected with multiple HPV types. Regarding healthy women, 8.5 and 2.1% were infected with single and multiple HPV types, respectively. The two most commonly detected HPV types were HPV 16 and 58 regardless of single- or multiple-type infection or source of the participants. HPV16 + 58 was the most commonly identified multiple genotype in outpatients, while HPV16 + 52 was frequently detected in healthy women. Highest prevalence rate was found in outpatients aged < 20 years and ≥ 60 years.ConclusionsThis study revealed the prevalence characteristics of HPV in both outpatient women and healthy women in Jiangsu province.

Human Papillomavirus (HPV) 16/18 E6 Oncoprotein Expression in Infections with Single and Multiple Genotypes.

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

Malignant Transformation of Fanconi Anemia Complementation Group D2-deficient (Fancd2 -/-) Hematopoietic Progenitor Cells by a Single HPV16 Oncogene.

To demonstrate that Fanconi anemia complementation group D2-deficient (Fancd2-/-) hematopoietic progenitor cell lines can be transformed by transfection with a plasmid containing either the E6 or E7 oncogene of human papillomavirus (HPV) to generate malignant plasmacytoma-inducing cell lines. In order to determine whether a single HPV type 16 (HPV16) oncogene induced malignant transformation, Fancd2-/- and Fancd2+/+ interleukin 3 (IL3)-dependent hematopoietic progenitor cell lines were transfected with plasmids containing E6 or E7 oncogene, or control empty plasmid. Fancd2-/- but not Fancd2+/+ cells were transformed into malignant IL3-independent cells by both E6, and E7 oncogenes, but not by empty plasmid. Hematopoietic cell lines and tumors induced by Fancd2-/- E6 and Fancd2-/- E7 cell lines were positive for each respective HPV RNA and protein. A single HPV16 oncogene is adequate to produce malignant transformation of Fancd2-/- hematopoietic cells.

Minor Capsid Protein L2 Polytope Induces Broad Protection against Oncogenic and Mucosal Human Papillomaviruses.

The amino terminus of the human papillomavirus (HPV) minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. A wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1-based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses. We also reported, however, that although protection is broad, some oncogenic HPV types escape the neutralizing antibody response, if L2 epitopes from single HPV types are used as immunogen. We were able to compensate for this by applying a mix of thioredoxin proteins carrying L2 epitopes from HPV16, -31, and -51. As the development of a cost-efficient HPV prophylactic vaccines is one of our objectives, this approach is not feasible as it requires the development of multiple good manufacturing production processes in combination with a complex vaccine formulation. Here, we report the development of a thermostable thioredoxin-based single-peptide vaccine carrying an L2 polytope of up to 11 different HPV types. The L2 polytope antigens have excellent abilities in respect to broadness of protection and robustness of induced immune responses. To further increase immunogenicity, we fused the thioredoxin L2 polytope antigen with a heptamerization domain. In the final vaccine design, we achieve protective responses against all 14 oncogenic HPV types that we have analyzed plus the low-risk HPVs 6 and 11 and a number of cutaneous HPVs.IMPORTANCE Infections by a large number of human papillomaviruses lead to malignant and nonmalignant disease. Current commercial vaccines based on virus-like particles (VLPs) effectively protect against some HPV types but fail to do so for most others. Further, only about a third of all countries have access to the VLP vaccines. The minor capsid protein L2 has been shown to contain so-called neutralization epitopes within its N terminus. We designed polytopes comprising the L2 epitope amino acids 20 to 38 of up to 11 different mucosal HPV types and inserted them into the scaffold of thioredoxin derived from a thermophile archaebacterium. The antigen induced neutralizing antibody responses in mice and guinea pigs against 26 mucosal and cutaneous HPV types. Further, addition of a heptamerization domain significantly increased the immunogenicity. The final vaccine design comprising a heptamerized L2 8-mer thioredoxin single-peptide antigen with excellent thermal stability might overcome some of the limitations of the current VLP vaccines.

Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts

Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV.

Prevalence of and Risk Factors for Oral Human Papillomavirus Infection With Multiple Genotypes in the United States.

This study investigated the prevalence of and risk factors for oral human papillomavirus (HPV) infection with multiple genotypes in the United States. Data were from the nationally representative 2009-2012 National Health and Nutrition Examination Survey. This analysis comprised 9257 participants for whom data on oral HPV (37 genotypes) and associated risk factors were available. The weighted prevalence of multitype (2-6 types) oral HPV infection was 1.5% (2.5% for men, 0.4% for women) in the whole sample and 19.7% (22.0% for men, 12.1% for women) in those who had any type of oral HPV positivity. Most multitype oral HPV cases (83.8%) harbored one or more oncogenic types. In the adjusted multinominal logistic regression model, being male (relative risk ratio [RRR] = 3.69; 95% confidence interval [CI], 1.57-8.65), being a current cigarette smoker (RRR = 2.57; 95% CI, 1.23-5.36), and having a new sex partner in the past year (RRR = 2.10; 95% CI, 1.03-4.28) were associated with an increased risk of multitype oral HPV infection over single-type HPV infection. Men, smokers, and those who had new sexual partners were at a significantly higher risk for multitype oral HPV infection.

Prevalence of human papillomavirus infection among 71,435 women in Jiangxi Province, China.

Cervical cancer is the third most common cancer in women worldwide. Human papillomavirus (HPV) has been identified as an etiological factor for cervical cancer. Data on the prevalence and subtype distribution of HPV infection in Jiangxi Province are incomplete. In this study, we investigated HPV subtype distribution and prevalence in Jiangxi Province between August 1, 2010, and December 31, 2015. A total of 71,435 individuals ranging in age from 16 to 77 years were recruited. Cervicovaginal swabs were collected from each participant, and HPV screening was performed. Our results showed that the HPV prevalence was 22.49% in Jiangxi Province. Overall, 14.99% of individuals were positive for a single HPV type, and 7.49% were positive for multiple types. The most frequently detected low-risk genotypes were HPV-6, and high-risk genotypes were HPV-16, -18, -33, -52, and -58. The prevalence and type distribution of HPV infection exhibits regional and age differences; Yingtan had the highest incidence for high-risk HPV infection (32.00%), and peaks in the frequencies of HPV infections were seen for patients under 20 and over 60 years of age. In conclusion, we present data showing that the HPV prevalence varies significantly with age and regions in Jiangxi Province. These results can serve as valuable reference to guide Jiangxi cervical cancer screening and HPV vaccination programs.

Male Partners of Infertile Couples with Seminal Infections of Human Papillomavirus Have Impaired Fertility Parameters.

Several studies have addressed the impact of viral infections on male infertility. However, it is still unknown whether human papillomavirus (HPV) can alter seminal parameters. The aim of this study was to determine the prevalence of HPV in the semen of male partners of couples seeking fertility evaluation. Additionally, we assessed the possibility that HPV infections affect seminal parameters. A total of 229 semen samples were collected from men in the Sperm Analysis Section of São Camilo Laboratory of Maringá, Brazil, between October 2015 and March 2016. Basic seminal parameters were analyzed, and HPV was detected and genotyped by polymerase chain reaction. HPV DNA was detected in 16.6% of samples. Of these, 10.5% had single type HPV infections, 6.1% had multiple HPV infections, 5.7% had exclusively high-risk HPV, and 6.1% had exclusively low-risk HPV. Samples positive for single and multiple types of HPV were associated with abnormal viscosity, and samples positive for multiple HPV types were also associated with hypospermia, higher pH, and increased leukocyte numbers. These findings suggest that the male partners of infertile couples with seminal HPV infections may have prostate disturbances indicative of glandular dysfunction, which may influence fertility.