OBJECTIVETo evaluate the diagnostic applicability of human papillomavirus (HPV) liquid chip assay which is based on Luminex XMAP System, and perform a HPV epidemiologic study with the liquid chip in women of Shandong province.

METHODSTo detect HPV genotypes on a 96-well plate with the liquid chip which can simultaneously detect and identify 26 common HPV genotypes in a total of 2925 cervical scrapes obtained from gynecological outpatients as well as to analyze the relationship between HPV types and different cervical diseases by studying the distribution of HPV genotypes and pathologic diagnosis.

RESULTSAmong 639 cases who performed pathologic/cytological and histological diagnoses, 184 cases are in group of normal cytology, 266 cases in group of, 77 cases in group of cervical intra-epithelial neoplasia (CIN) I, 7 cases in group of CIN I - II, 46 cases in group of CIN I - II, 46 cases in group of CIN I - II and 13 cases in group of cervical cancer. The overall incidence of HPV in our samples is 36.0% (1054/2925) and 23 types of all 26 types on liquid chip are found. The most common genotypes found are HPV-16 (26.75%), HPV-52 (25.75%), HPV-58 (10.47%), HPV-18 (8.87%) and HPV-11 (6.94%). Among all the positive types, 87.32% are high-risk HPV and 13.68% are low-risk HPV genotypes. Both single and multiple types are easily identified, showing 66.22% ( n = 698) single type and 33.78% ( n = 356) multiple types. Of all the 1054 HPV-positive cases, 261 (24.8%) is occupied by women 21 to 25 years of age and progressively lower by older age groups, reaching 4.9% by women between 51 to 67 years old. The incidence of HPV in our samples is 23.37%, 33.08%, 54.54%, 57.14%, 82.61%, 91.30% and 100% for normal cytology, inflammation,CIN I ,CIN I - II, CIN II ,CIN III, and carcinomas specimens, respectively. Infections with more that one virus are common, accounted for 4.89%, 7.14%, 18.18%, 28.57%, 41.30%, 43.37% and 38.46% for normal cytology, inflammation, CIN I, CIN I - II, CIN II, CIN III, and carcinomas specimens, respectively. Based on the criteria of histology and pathology, the sensitivity, specificity, positive-predictive value and negative-predictive value of HPV liquid chip assay for detecting all cases of CIN II, III are 88.57%, 76.63%, 68.89% and 92.16% respectively. Conclusion The common types of HPV infection are 16, 52, 58, 18, 11, 6, 56 and 31. The HPV-positive rate increased along with the increase of grading on cervical lesions. There are more younger women among all the HPV-positive ones. Multiplex HPV genotyping by liquid chip appears to be highly suitable for diagnostic screening as well as the conduction of large-scale epidemiological studies.

Adolescent ; Adult ; Aged ; Cervical Intraepithelial Neoplasia ; epidemiology ; virology ; China ; epidemiology ; Female ; Gammapapillomavirus ; classification ; genetics ; Genotype ; Human papillomavirus 11 ; classification ; genetics ; Human papillomavirus 16 ; classification ; genetics ; Human papillomavirus 18 ; classification ; genetics ; Human papillomavirus 6 ; classification ; genetics ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; methods ; Papillomaviridae ; classification ; genetics ; Papillomavirus Infections ; epidemiology ; virology ; Uterine Cervical Neoplasms ; epidemiology ; virology ; Young Adult

The necessary role of genital infection by specific types of human papillomavirus (HPV) in cervical cancer development provides an opportunity to reduce the risk of cervical cancer, a second leading cancer in women, through prophylactic vaccination. Two types of vaccines targeting HPV 16 and 18 which are responsible for about 70% of all cervical cancer worldwide have been developed: a quadrivalent vaccine (Gardasil?) and a bivalent vaccine (Cervarix?). Gardasil also targets HPV 6 and 11 causing 90% of genital wart. Both two vaccines contain virus-like particles composed of L1 protein of viral capsid and do not exert infectivity. HPV vaccines were highly effective in preventing persistent infection by vaccine specific type HPV in young women who have not been previously exposed to them. Randomized double-blind placebo-controlled clinical trials have provided evidence that HPV vaccines have high efficacy against cervical precancerous lesion in young women irrespective of baseline HPV infection status. However, HPV vaccines neither treat existing HPV infections nor provide protection against all types of HPV related with cervical cancer. Therefore, even vaccinated females should take cervical cancer screening as recommended. Gardasil has been tested mainly in 9~26 years old females and Cervarix in 15~25 years old. Current recommendation for vaccination age is 9~26 years for Gardasil and 10~25 years for Cervarix, considering sexual debut and previous clinical trials. There are plenty of remaining issues regarding HPV vaccination such as vaccine efficacy in older women and in males, cost-effectiveness, duration of protection, cross-protection, potential replacement infection, and vaccine compatibility.
Cancer Vaccines ; Capsid ; Condylomata Acuminata ; Female ; Human papillomavirus 16 ; Human papillomavirus 18 ; Human papillomavirus 6 ; Humans ; Male ; Mass Screening ; Papillomavirus Vaccines ; Uterine Cervical Neoplasms ; Vaccination ; Vaccines ; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Human papillomavirus (HPV) infection causes virtually all cases of cervical cancer, the second most common cause of death from cancer among women worldwide. The ability to generate human papillomavirus virus (HPV)-like particles by the synthesis and self-assembly in vitro of the major virus capsid protein L1 has transformed our prospects for preventing cervical carcinoma in women. These particles provide vaccines that are immunogenic and safe. Following preclinical research by laboratories in the nonprofit sector, Merck and GlaxoSmithKline are developing commercial versions of the vaccine. Both vaccines target HPV-16 and HPV-18, which account for approximately 70% of cervical cancer. The Merck vaccine also targets HPV-6 and HPV-11, which account for approximately 90% of external genital warts. Published data from proof of principle trials and preliminary reports from large Phase III efficacy trials suggest strongly that they will protect against persistent HPV infection and cervical intra-epithelial neoplasia. However, the duration of protection provided by these vaccines is not known, the antibody responses induced are probably HPV type specific and immunisation should occur pre-exposure to the virus. Unresolved issues also include the most critical groups to vaccinate and when the vaccine's cost may be low enough for widespread implementation in the developing world, where 80% of cervical cancer occurs. Nevertheless, it may be that an HPV vaccine that protects against the complications of HPV infection such as cervical cancer will be one of the most significant public health initiatives of this decade.
Antibody Formation ; Capsid Proteins ; Cause of Death ; Condylomata Acuminata ; Female ; Human papillomavirus 11 ; Human papillomavirus 16 ; Human papillomavirus 18 ; Human papillomavirus 6 ; Humans* ; Papillomavirus Vaccines* ; Public Health ; Uterine Cervical Neoplasms ; Vaccines

Human papilloma virus (HPV) vaccine is designed to prevent cervical cancer by preventing HPV infection of the uterine cervix. HPV vaccines are made of virus-like particles which are composed of L1 protein of viral coats. Two HPV vaccines have been developed. "Cervarix" is a bivalent vaccine which contains L1 protein of HPV 16 and HPV 18, and "Gardasil" is a quadrivalent vaccine which contained L1 protein of HPV 6 and HPV 11 in addition to HPV16 and HPV18. Clinical studies showed that both vaccines are highly effective to prevent cervical, vaginal and vulvar precancerous lesion in the population who are naive to HPV infection. Furthermore quadrivalent vaccine showed high efficacy to prevent genital warts. Efficacy of the vaccine decreased in total population who included both HPV-naive and HPV-infected people. Both vaccines demonstrated immune responses and immune memory up to 5 years. Safety studies showed no demonstrable major adverse reaction. From the public health standpoint, HPV vaccine is an important vaccine for young adolescent girls who have not begun sexual activities. Efficacy for mid-aged women needs more evidence based on pathology-based efficacy studies.
Adolescent ; Cervix Uteri ; Condylomata Acuminata ; Female ; Human papillomavirus 11 ; Human papillomavirus 16 ; Human papillomavirus 18 ; Human papillomavirus 6 ; Humans ; Memory ; Papilloma ; Papillomavirus Vaccines ; Public Health ; Sexual Behavior ; Uterine Cervical Neoplasms ; Vaccines ; Viruses

AIMThere is an increasing evidence for the role of high risk human papillomavirus (HPV) in the pathogenesis of oral squamous cell carcinoma (OSCC). The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC.

METHODOLOGYFifty-two patients with OSCC were followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified in formalin-fixed, paraffin-embedded tumor specimens by nested PCR with MY09/MY11 and GP5+/GP6+ primer pairs and the HPV genotype was determined by direct DNA sequencing. Association between the HPV status and risk factors for cancer as well as tumor-host characteristics were analyzed. Survival curves were calculated by the Kaplan-Meier method and analyzed using the log-rank test.

RESULTSHPV was found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%, HPV6 for 3.9% and HPV11 for 1.8%. No infection with more than one HPV genotype was detected. HPV infection was significantly associated with poor histological grade, TNM stage I-II, alcohol usage and no smoking status. Multivariate analysis showed that HPV had an independent prognostic effect on the overall survival after adjusting other confounding factors such as histological grade, TNM stage and tobacco usage. The presence of HPV was significantly correlated with a better survival in patients with OSCC.

CONCLUSIONHPV infection can act as an independent predictor for the survival and prognosis of OSCC.

Alcohol Drinking ; Alphapapillomavirus ; classification ; physiology ; Carcinoma, Squamous Cell ; virology ; Cause of Death ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Forecasting ; Genotype ; Human papillomavirus 11 ; isolation & purification ; physiology ; Human papillomavirus 16 ; isolation & purification ; physiology ; Human papillomavirus 18 ; isolation & purification ; physiology ; Human papillomavirus 6 ; isolation & purification ; physiology ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; virology ; Neoplasm Staging ; Papillomavirus Infections ; virology ; Prognosis ; Risk Factors ; Sequence Analysis, DNA ; Smoking ; Survival Rate

Objective: To determine the prevalence of HPV high risk positivity among women patients ages 30 to 65 with biopsyproven external genital warts (condyloma acuminata) specifically for HPV 16, HPV 18, and for other high risk types 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66/68, 73, and 82. Methodology: A cross-sectional study was conducted at the Department of Obstetrics and Gynecology Out-Patient Services of the Philippine General Hospital involving 57 women, 30 to 65 years old, with biopsy proven external genital warts or condyloma acuminata. These women underwent human papillomavirus (HPV) genotyping test for the high risk types (HR-HPV) from cervical samples using the automated polymerase chain reaction (PCR) technology. Results: Fifteen out the 57 subjects had at least one of the HR-HPV types for an overall prevalence of 26.3%. Of the 15, 8 (53.3%) had at least 2 HR-HPV types with one subject having the most number of types at 6. Among the strains, the most common is HPV 51 and 52 each with a prevalence of 8.77% followed by HPV 53 and 59 at 7% each. HPV 16 and 18 each only had a 3.5% prevalence the same as HPV 58, 73, and 82. HR-HPV positivity was most common in the 30 to 39 age group (80%), and equally in the nulligravid and the secundigravid (40% each). None had current or past cigarettesmoking history and 33% had some form of hormonal contraception. Conclusion The overall prevalence of high risk HPV (HR-HPV) among these 57 Filipino women with external genital warts is 26.3%. The higher prevalence of HPV 51, 52, 53, and 59 over HPV 16 and 18 in this group does not follow the usual epidemiological characteristics reported about this disease.
Outpatients ; Human papillomavirus 16 ; Philippines ; Papillomaviridae

Further understanding of male human papillomavirus (HPV) infection is necessary to prevent infection in men, as well as transmission to women. In our current study, we investigated patterns of HPV infection and genotype distributions in male genital warts using the Anyplex II HPV28 Detection kit. We reviewed the medical records of 80 male patients who presented to 5 neighborhood clinics in Ulsan, Korea, for the treatment of genital warts between April 2014 and January 2015. All patients underwent HPV genotyping. The prevalence and characteristics of HPV infection were analyzed, and the patterns of HPV infection according to age were assessed. Among the study patients, 13 (16.3%) were negative for HPV infection, 46 (57.3%) were infected with low-risk HPV, and 21 (26.3%) were infected with high-risk HPV. Patients with multiple HPV infection were more likely to have high-risk HPV infection (P = 0.001). The prevalence of HPV infection was much higher in samples obtained by tissue excision due to a definite lesion (P = 0.001). There were no differences in high-risk HPV infection (P = 0.459), multiple HPV infection (P = 0.185), and recurrence at diagnosis (P = 0.178) according to age. HPV-6 and HPV-11 were the most common type overall (39.7% and 13.8%, respectively). HPV-16 and HPV-18 were the most common high-risk infections (both 3.4%). HPV infection is not only commonly encountered in male genital warts, but is also accompanied by high-risk HPV and multiple infections.
Adult ; Condylomata Acuminata/epidemiology/*pathology/virology ; DNA, Viral/genetics/metabolism ; Genotype ; Human papillomavirus 11/*genetics/isolation & purification ; Human papillomavirus 16/genetics/isolation & purification ; Human papillomavirus 18/genetics/isolation & purification ; Human papillomavirus 6/*genetics/isolation & purification ; Humans ; Male ; Middle Aged ; Prevalence ; Real-Time Polymerase Chain Reaction ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors

BACKGROUND: We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). METHODS: All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. RESULTS: Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. CONCLUSIONS: For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.
Adult ; Aged ; Cervix Uteri/pathology/virology ; DNA, Viral/analysis ; Female ; Genotype ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Humans ; Middle Aged ; Papillomaviridae/*genetics/isolation & purification ; Papillomavirus Infections/*diagnosis/pathology/virology ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Young Adult

OBJECTIVE: Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. METHODS: The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. RESULTS: Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; p<0.001) and 2.4 (95% CI, 1.4 to 4.3; p<0.001), respectively, while that of the HPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). CONCLUSION: The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion.
Adult ; Cervical Intraepithelial Neoplasia/*virology ; Colposcopy ; DNA, Viral/analysis ; Female ; *Genotype ; Human papillomavirus 16/genetics ; Human papillomavirus 18/genetics ; Humans ; Middle Aged ; Papanicolaou Test ; Papillomaviridae/*genetics ; Papillomavirus Infections/*virology ; Risk Factors ; Uterine Cervical Neoplasms/virology ; Vaginal Smears

OBJECTIVETo study the expression of Skp2 in cervical squamous cell carcinoma (SCC) and its precancerous lesions, and to investigate its relationship with human papillomavirus (HPV) infection.

METHODSThe expression of Skp2 protein and HPV16/18 DNA was determined using immunohistochemistry and in-situ hybridization in 30 cases of normal cervical squamous epithelium, 29 cases of low-grade intraepithelial neoplasia, 31 cases of high-grade intraepithelial neoplasia and 31 cases of cervical SCC.

RESULTSSkp2 expression was not detected in normal cervical squamous epithelium and no significant difference was obtained statistically on Skp2 expression between normal cervical squamous epithelium and low-grade intraepithelial neoplasia (P > 0.05). However, the expression of Skp2 gradually increased with elevation of epithelial lesion grading in an order from low to high grade and to cervical SCC (P < 0.01). The positive rate of HPV16/18 DNA in cases of normal cervical squamous epithelium, low-grade, high-grade intraepithelial neoplasia and cervical SCC was significantly different (P < 0.01), although both high-grade intraepithelial neoplasia and cervical SCC had a similar high HPV infection rate up to 96.8%. There was no correlation obtained between Skp2 expression and HPV16/18 infection in low-grade intraepithelial neoplasia. In contrast, expression of Skp2 and HPV infection were significantly correlated in both high-grade intraepithelial neoplasia and cervical SCC (gammaH = 0.373, gammaC = 0.416, P < 0.05).

CONCLUSIONSAbnormal expression of Skp2 is present mainly in high-grade cervical intraepithelial neoplasia and invasive carcinoma, which may be considered as a surrogate marker for the high-grade lesions. Skp2 may play a key role in the development of cervical squamous carcinoma induced by HPV16/18 infection, through E7-Skp2-Rb signaling pathway.

Carcinoma ; pathology ; virology ; Carcinoma, Squamous Cell ; etiology ; virology ; Cervical Intraepithelial Neoplasia ; Female ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans ; Immunohistochemistry ; Papillomaviridae ; Papillomavirus Infections ; complications ; Uterine Cervical Neoplasms ; pathology ; virology