The frequency of herpes simplex virus changes in anal Pap smear and its association with squamous intraepithelial lesions in high‐risk male patients

While there are studies postulating a model of synergism between human papillomavirus (HPV) and herpes simplex virus (HSV) in cervical carcinogenesis, the frequency of anal herpes as well as its association with anal squamous intraepithelial lesions (ASILs) has been understudied in men. This study evaluates the frequency of HSV changes in anal Pap smears and its association with ASILs in a high‐risk population. A computerized search for specimens associated with anal cytology that had positive findings of HSV was performed. The electronic medical records were examined for past diagnosis of herpes, HSV serology prior to or after cytology, and if the patient received treatment after cytologic diagnosis of HSV. Of the 470 anal Pap smears (Thin‐prep) examined, seven had cellular changes consistent with HSV infection. All patients were asymptomatic human immunodeficiency virus (HIV) positive males with no prior HSV serology tests. Two patients had prior diagnoses of HSV infection. Cytologic abnormalities were identified in 86% ranging from atypical squamous cells of undetermined significance to high grade squamous intraepithelial lesion. Three patients were treated after the HSV cytologic diagnosis. The frequency of HSV changes in anal Pap smear is low (1.48%), but the presence of concomitant cytologic abnormalities is high (86%). While our findings suggest the possible role of HSV as a HPV co‐factor in ASILs, larger studies are needed to support this. Identification of HSV infection on anal Pap smear is important for institution of patient treatment and subsequent reduction of transmission. Diagn. Cytopathol. 2014;42:487–490. © 2013 Wiley Periodicals, Inc.     

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

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

宫颈鳞状细胞癌和癌前病变中Skp2表达及其与HPV16/18感染的关系

目的 探讨skp2在宫颈鳞状细胞癌和癌前病变中的表达规律及其与人乳头状瘤病毒(HPV)感染之间的关系.方法 采用免疫组织化学(ABC法)和原位杂交检测Skp2蛋白和HPV16/18 DNA在30例正常宫颈鳞状上皮、29例宫颈低级别上皮内瘤变、31例高级别上皮内瘤变和31例宫颈鳞状细胞癌中的表达.结果 Skp2在正常宫颈鳞状上皮中呈阴性,与宫颈低级别上皮内瘤变(阳性表达率为13.8%,4/29)之间差异无统计学意义(P>0.05).随着上皮病变级别升高,表达也逐渐增强,在宫颈鳞状细胞癌中表达更强;HPV16/18 DNA在四组中的阳性表达率,除高级别上皮内瘤变和宫颈鳞状细胞癌两组间差异无统计学意义外(均为96.8%),其余各组之间差异均有统计学意义(P<0.01);在宫颈低级别上皮内瘤变中skp2蛋白表达和HPV感染相关无统计学意义,但在高级别上皮内瘤变和宫颈鳞状细胞癌两组中均呈正相关(γ高级别=0.373,γ癌 =0.416,P<0.05).结论 Skp2过表达主要在宫颈鳞状细胞癌形成的中晚期起作用,可作为一个早期诊断恶性的指标,且可能与HPV16/18感染有协同作用.E7-skp2-Rb可能是HPV感染诱导宫颈鳞状细胞癌形成的一条新致癌途径.     

Low CD4 cells and viral co-infection increase the risk of VaIN: Use of SCCA1 and Ki67 as diagno-prognostic biomarkers

This study evaluated the correlation of SCCA1, Ki67 and CD4 cell expressions and classified vaginal smears in individuals co-infected with Human immunodeficiency virus (HIV), Herpes simplex virus 2 (HSV2), Epstein Barr virus (EBV) and Human Papilloma virus (HPV). This crossectional study included 173 participants within the age range of 20–70 years. Vaginal smears were stained by Papanicolaou technique and classified into high-grade squamous cell intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), atypical squamous cells of undetermined significance (ASCUS) and negative for intraepithelial lesion (NIL). Presence of immunoglobulin M and G antibodies for EBV, HIV, HPV and HSV2, and SCCA1 and Ki67 antigens were determined by ELISA method. Result showed that biomarkers SCCA1 had higher sensitivity (87.5%) to vaginal lesions when compared with Ki67 which had a sensitivity of 70.8% (p?>?.01). Assays revealed viral co-infections of 96.0% and 16.8% in smears positive and negative for vaginal lesions, respectively (p?<?.01) with HIV, HSV2 and EBV as the most prevalent type of co-infection (36%). The findings of this study suggest that low CD4 cells and viral co-infection could increase the risk of developing vaginal lesions. This study also suggests that SCCA1 and Ki67 could be used as diagnostic and prognostic biomarkers for vaginal intraepithelial neoplasia (VaIN).     

Effect of herpes simplex virus on the DNA of human papillomavirus 18

Some types of human papillomaviruses (HPV) appear to be associated with carcinoma of the cervix or other tissues, but patients infected with HPV do not necessarily develop carcinoma. Some epidemiological studies of risk factors for cervical carcinoma have indicated the involvement of herpes simplex virus (HSV). To study the effect of HSV on the genome of HPV, total DNAs were extracted and analyzed after HeLa cells, or A431 cells, transiently transfected with HPV18 DNA, were infected with HSV-1 or -2 for 24 hours. In HeLa cells, integrated HPV18 DNA was amplified almost threefold. In A431 cells, HPV 18 DNA fragments, sensitive to the restriction enzyme Mbo I, indicated newly replicated DNA. Replication intermediates were detected when the DNA was resolved by two-dimensional gel electrophoresis. This study showed that HSV caused some amplification of HPV and indicated the possibility of HSV involved in the integration and amplification of HPV in host cells. J. Med. Virol. 53:4–12, 1997. © 1997 Wiley-Liss, Inc.     

Factors affecting residual/recurrent cervical intraepithelial neoplasia after cervical conization with negative margins

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high‐grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow‐up comprised clinical examination, a liquid‐based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy‐directed punch biopsy. The Kaplan‐Meier method was used to analyze the median recurrent time, whereas log‐rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow‐up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow‐up (P = .000) had an increased risk of residual/recurrent CIN. During follow‐up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.     

Human papillomavirus infection among women attending family planning clinic in Nigeria: prevalence,correlates, and co-infection with Chlamydia trachomatis

Infection with high-risk genotypes of human papillomavirus (HPV) is considered the main cause of invasive cervical. A number of epidemiologic studies have suggested that HPV and Chlamydia trachomatis (CT) play a synergistic role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. The current study aimed to evaluate the HPV prevalence and the risk factors for co-infection with CT among women attending family planning clinic in Nigeria. Following enrolment, 90 patients were screened for IgG antibodies to virus-like proteins of HPV types 6, 8, 16, and 18. CT seropositivity was tested by enzyme-linked immunosorbent assay for the detection of IgG and IgM antibodies. The prevalence of HPV IgG was 20%. Seropositivity for CT IgM was 77.8% while the IgG was 0%. A total of 10 women (11.1%) were seropositive for both CT IgM and HPV IgG antibodies. Seropositivity for HPV IgG was significantly associated with age at marriage (P < 0.001), current Chlamydia infection (P < 0.011), and number of children (P < 0.025), while seropositivty for HPV IgG and Chlamydia trahomatis IgM was significantly associated with age at coitarche (P < 0.028), number of life sex partners (P < 0.033), and history of multiple sexual partners (P < 0.002).     

Detection of Chlamydia trachomatis and herpes simplex virus type 1 or 2 in cervical samples in human papilloma virus (HPV)-positive and HPV-negative women

This study investigated whether the prevalence of human papilloma virus (HPV) in association with Chlamydia trachomatis, herpes simplex virus (HSV)-1 and/or HSV-2 was greater in high-grade than in low-grade or control cervical biopsy specimens. HPV-positive (n = 86) and HPV-negative (n = 213) women were screened for HPV, HSV and C. trachomatis by PCR. The most common HPV genotypes were HPV-16, HPV-6 and HPV-33; mixed HPV infection (n = 12) was also seen. A higher prevalence of C. trachomatis, HSV-1 and HSV-2 was found in HPV-positive samples. High-risk HPV genotypes and combined HPV + C. trachomatis or HPV + HSV-1, but not HSV-2, infections were associated with a greater risk of developing cervical carcinoma.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or cervical intraepithelial neoplasia in Henan province,central China

To evaluate the prevalence of human papillomavirus (HPV) infection and its genotype among women with cervical lesions in Henan Province, central China. A total of 1317 cervical scrapes from patients with cervical intraepithelial neoplasia 1 (CIN1) (n = 91), CIN2/3 (n = 466), and cervical cancer (CC; n = 760) were collected from 2013 to 2018, and then tested for HPV genotypes using polymerase chain reaction followed by flow-through hybridization assay. The prevalence of HPV was 62.64% for patients with CIN1, 86.91% for patients with CIN2/3%, and 89.21% for patients with CC. In total, the HPV prevalence was 86.56%, and the most common HPV type was HPV16 (58.77%) followed by HPV58 (10.33%), 18 (7.67%), 52 (6.61%), and 33 (5.54%). In this study, the high-risk HPV cumulative attribution rate of nine-valent vaccine coverage was markedly higher than that of bivalent or quadrivalent vaccine coverage in each histopathological category or overall (P < .001). Single HPV infection was the main infection category in each histopathological diagnosis, and the total infection rate was 65.83% (867/1317; P < .001). The prevalence of HPV16 or single HPV infection increased with the severity of cervical lesions (P < .001). HPV16, 58, 18, 52, and 33 may be predominant high-risk factors for cervical lesions in Henan Province. The nine-valent prophylactic HPV vaccine is more effective than a bivalent or quadrivalent vaccine for protecting women from CC in the region.     

宫颈癌中α-enolase表达及其与HPV感染的关系

目的探讨烯醇化酶-α(α-enolase)蛋白在宫颈鳞癌中的表达及其与HPV感染的关系。方法应用免疫组化PV-9000两步法检测30例慢性宫颈炎、61例宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和70例宫颈鳞癌组织中α-enolase蛋白的表达,同时应用基因芯片技术检测70例宫颈鳞癌中HPV感染情况。结果 (1)α-enolase蛋白表达于细胞质和(或)胞核中。在慢性宫颈炎、CIN和宫颈癌中,α-enolase蛋白在胞质表达的阳性率分别为4.17%(1/24)、18.5%(10/54)和54.3%(38/70),表达依次增强(P=0.000)。(2)宫颈癌中HPV总感染率为97.1%(68/70),共检出8种HPV基因型,分别为HPV16、18、58、31、52、59、66、68,构成比为80.0%、14.3%、4.3%、4.3%、2.9%、2.9%、1.43%、1.43%。双重感染10例,占14.3%。HPV16、18为主要致病基因型。(3)宫颈癌中α-enolase蛋白表达的定位与HPV16/18感染呈正相关(r=0.340,P=0.012)。结论宫颈鳞癌中α-enolase蛋白表达与HPV16/18感染密切相关,二者在宫颈鳞癌的发生过程中可能起着协同作用。     

Detection of torque teno midi virus/small anellovirus (TTMDV/SAV) in chronic cervicitis and cervical tumors in Isfahan,Iran

Torque teno midi virus and small anellovirus (TTMDV/SAV) are members of the genus Gammatorquevirus within the family Anelloviridae. Cervical cancer is the second most prevalent cancer after breast cancer. The aim of this study was to determine the frequency of infection by these viruses in cervicitis and cervical tumors of women from Isfahan, Iran. Formalin-fixed, paraffin-embedded tissue samples from cervical cancers (n = 42) and cervicitis cases (n = 79) were subjected to nested PCR to identify TTMDV/SAV viral sequences. Of the 42 tumor cases, 22, 18 and 2 were diagnosed as adenocarcinoma, cervical intraepithelial neoplasia and squamous cell carcinoma, respectively. In total, 23 (55%) of the tumor samples were positive for TTMDV/SAV. Of the 79 cervicitis cases, 38 (48%) were also positive for TTMDV/SAV. This is the first report of TTMDV/SAV in cervicitis and cervical tumors of women.     

Variability of polymerase chain reaction-based detection of human papillomavirus DNA is associated with the composition of vaginal microbial flora

The results of repeated human papillomavirus (HPV) DNA testing were compared to changes in cervical pathology and the composition of vaginal microorganisms. A cohort of 19 women with HPV cervical infections in the absence of cervical intraepithelial neoplasia at enrollment was reexamined on average at 7.3-month intervals over a 2-year period. At each follow-up visit, cytological and colposcopic examinations were done and vaginal microorganisms were assessed quantitatively by Gram staining of secretions, and anaerobic and aerobic culture. HPV genotypes 6, 11, 16, and 18 were detected by polymerase chain reaction analysis using DNA isolated from exfoliated cervical cells. The detection of HPV DNA was significantly associated with carriage of Grade II flora (P < 0.001), isolation of Gardner ella vagina/is (P = 0.03), Ureaplasma urealyti cum (P = 0.04), Candida albicans (P = 0.01), Bac teroides species (P = 0.01), and overgrowth by anaerobes (P = 0.004). Normal vaginal flora, characterised by the predominance of Lactoba cillus species, was significantly associated (P < 0.001) with a negative HPV test. The detection of HPV DNA is associated with the composition of microorganisms present in the vagina at the time of testing. © 1994 Wiley-Liss, Inc.     

Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16(INK4A) overexpression and clinicopathological correlations

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J
(2010) Histopathology 57, 907–916 Primary squamous cell carcinoma of the vagina: human papillomavirus detection, p16 ^INK4A overexpression and clinicopathological correlations Aim: To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance. Methods and results: All cases of SCCVa diagnosed over a 15‐year period from two hospitals in Barcelona, Spain (n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV‐positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P = 0.01). HPV‐positive tumours were more frequently of non‐keratinizing, basaloid or warty type than HPV‐negative neoplasms (84% versus 14.3%; P < 0.001), and showed diffuse positive immunoreactivity for p16^INK4a (96%, versus 14.3%; P < 0.001). The sensitivity and specificity of p16 to identify HPV‐positive tumours were 96% and 85.7%, respectively. Conclusions: A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV‐positive tumours tend to affect women with history of cervical neoplasia.     

维吾尔族妇女宫颈癌人乳头状瘤病毒感染与人类白细胞抗原Ⅰ类基因表达缺失的关系及其意义

目的 研究维吾尔族妇女宫颈癌中人乳头状瘤病毒(HPV)感染和人类白细胞抗原Ⅰ类(HLA-Ⅰ)家族基因HLA-A、B和C表达的关系,探讨HPV感染和HLA-Ⅰ类家族基因表达缺失在宫颈癌演进过程中的作用.方法 收集维吾尔族妇女宫颈炎、宫颈上皮内瘤样病变(CIN)Ⅰ/Ⅱ/Ⅲ和宫颈鳞癌患者的新鲜组织标本共78例,提取总RNA,采用半定量RT-PCR方法鉴定HLA-A、B和C基因的mRNA表达水平.提取组织DNA,采用HPV通用引物和HPV分型芯片确定HPV亚型.结果 HLA-A、B和C基因的总体mRNA表达缺失率随着宫颈病变的加重而增加,在宫颈炎组织内为1/12,在CIN及宫颈鳞癌分别占70.0%(14/20)和84.8%(39/46),在恶性程度高的低分化癌组织中高达90.6%(29/32),并与高危型HPV16感染呈正相关(r=0.803,P＜0.01).结论 HLA-Ⅰ类基因的表达缺失是维吾尔族妇女宫颈癌发生的重要标志,而HPV16感染可能是HLA-Ⅰ分子表达缺失的前提条件.     

Prevalence of human papillomavirus genotypes and associated cervical squamous intraepithelial lesions in HIV-infected women in Botswana

Human papillomaviruses (HPV) constitute one of the most prevalent sexually transmitted infections and are the etiological agents for invasive cervical cancer, the predominant cancer among women in Botswana. However, the prevalence of HPV genotypes in Botswana has yet to be reported. One hundred thirty‐nine endocervical swabs were taken at baseline from HIV‐1 infected, HSV‐2 seropositive women enrolled in a longitudinal cohort study designed to assess the influence of herpes simplex virus‐2 (HSV‐2) infection on genital tract shedding of HIV‐1. Extracted DNA was evaluated for the presence of low‐risk and high‐risk HPV using the Roche Linear Array. Genotyping identified HPV in 95 of 139 women of which 61/95 were infected with high‐risk HPV and 56/95 with low‐risk HPV. The median number of genotypes was 2 (IQR: 1–4). The most prevalent HPV genotype in HIV‐infected women was HPV 58. Abnormal cervical cytology was detected in 87/127 women and was associated with contemporaneous HPV infection (RR = 1.43, 95% CI: 1.05–1.93; P = 0.02). HPV prevalence was high among HIV‐infected women with infection by multiple genotypes being widespread. The associations attributed to specific oncogenic HPV subtypes and cervical squamous intraepithelial lesions presented here provide critical information to inform future vaccine policy within Botswana. J. Med. Virol. 83:1689–1695, 2011. © 2011 Wiley‐Liss, Inc.     

Correlation between human papillomavirus infection and histopathological diagnosis of women in Northeast Brazil

Cervical carcinoma is the fourth leading cause of death among women worldwide. Epidemiological studies claim that human papillomavirus (HPV) infection is a necessary condition for cervical cancer development. Knowledge of the geographic distribution of HPV is important in guiding the introduction of prophylactic vaccines. This study analyzed the prevalence of HPV infection in cervical samples obtained from women with abnormal cervical histopathological diagnosis in Northeast Brazil. The study included an analysis of 211 women whose diagnosis was confirmed for cervical intraepithelial neoplasia type 1 (CIN-1), cervical intraepithelial neoplasia type 2 (CIN-2), cervical intraepithelial neoplasia type 3 (CIN-3), and cancer. The identification of the HPV genotypes was based on the polymerase chain reaction–restriction fragment length polymorphism technique. A total of 42.7% of the samples showed a single HPV infection, while 57.3% showed multiple infections. The most common genotypes detected were HPV-16, HPV-18, and HPV-31. HPV-16, HPV-31, HPV-35, and HPV-18 were the most common types in CIN-1 with a single infection. HPV-16 and HPV-18 were the most often found in CIN-2 with a single infection. HPV-16, HPV-18, and HPV-31 were the most detected in CIN-3 with a single infection. HPV-16 and HPV-31 were the most frequent in cancer with a single infection. Multiple infection with HPV-16 shows a 2.7 times greater risk of CIN-3 (P = .04). Multiple infections for HPV with HPV-16 and excluding the HPV18/31 types, were associated with CIN-3 (P = .01). The results allowed the detection and genotyping of HPV types circulating in the population studied. These findings must be taken into account when devising vaccination strategies against HPV.     

Diagnostic value of HMGB1 immunostaining on cell blocks from residual liquid‐based gynecologic cytology specimens

Aberrant expression of high mobility group box 1 (HMGB1) is associated with tumor development and progression. The current study was conducted to evaluate the significance of HMGB1 immunostaining on cell block (CB) preparations in the diagnosis of neoplastic and preneoplastic lesions of the cervix. The CBs were prepared from 157 residual liquid‐based gynecologic cytology specimens which were collected from women whose cervical lesions had been confirmed by histopathology. The expression of HMGB1 and p16INK4A (p16) was visualized by immunocytochemistry on the CB preparations, and the association of their expression patterns was correlated with the severity of cervical lesions. HeLa cells were used as positive control. HMGB1 expression was observed in dysplastic and neoplastic cells and increased along with the progression of cervical neoplasia. The rates of positive staining for HMGB1 in cervical intraepithelial neoplasia 1 (CIN‐1), CIN‐2, CIN‐3, and invasive squamous cell carcinomas (ISCCs) were 69.4, 96.9, 100.0, and 100.0%, respectively. The differences between positive rates of patients with chronic cervicitis and various CINs as well as ISCCs were significant (P < 0.005). The differences in positive staining rates between each two CIN groups, and differences between CIN‐1/2 and ISCCs, were also significant (P < 0.005). The expression pattern of HMGB1 was generally correlated with that of p16 (P < 0.001). HMGB1 staining was observed in some p16‐negative specimens. HMGB1 immunostaining on a CB from gynecologic cytology specimens is potentially valuable for the screening of cervical lesions in cases with questionable cytology. Diagn. Cytopathol. 2014;42:802–808. © 2014 Wiley Periodicals, Inc.     

HPV genotype prevalence in women with abnormal pap smears in Melbourne,Australia

Carcinoma of the cervix and its precursor, high‐grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time‐of‐treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (≥CIN3) (P < 0.006). Similarly, a significant increase in high‐risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR‐HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population. J. Med. Virol. 81:1283–1291, 2009. © 2009 Wiley‐Liss, Inc.     

Nucleoporin 88 expression in normal and neoplastic squamous epithelia of the uterine cervix

This study investigated the expression of nucleoporin 88 (Nup88) in formalin-fixed, paraffin-embedded archival tissues of cervical specimens consisting of normal ectocervical squamous epithelia (n = 34), low-grade squamous intraepithelial lesions corresponding to cervical intraepithelial neoplasia (CIN) 1 (n = 9), high-grade squamous intraepithelial lesions corresponding to CIN2 and CIN3 (n = 28), and invasive squamous cell carcinoma (ISCC; n = 30) to determine whether expression of this factor is involved in the progression of the morphological spectrum from normal cervical epithelia to CIN and cervical ISCC. A standard immunohistochemical technique was performed using a Ventana BenchMark XT immunostainer with a mouse antihuman monoclonal antibody to Nup88. Immunostaining was scored with regard to quantity and intensity of positively stained cells, with final immunoscores from 0 to 12 in each case. Nucleoporin 88 immunoscores increased significantly from normal ectocervical squamous epithelia to CIN1, CIN2/3, and ISCC (P < .0001, analysis of variance). Cervical intraepithelial neoplasia 2/3 as isolated lesions and adjacent to ISCC did not differ significantly. A significant correlation was noticed for immunoscores of CIN2/3 adjacent to ISCC and the corresponding ISCC (P = .0007). This study indicates that Nup88 is significantly overexpressed in high-grade CIN lesions and ISCC compared with normal ectocervical squamous epithelia and CIN1. However, Nup88 evaluation is of limited value as a diagnostic marker in individual cases.     

子宫颈病变组织中低分子量蛋白酶体表达与HPV16感染的关系

目的观察低分子量蛋白酶体(low molecular-weight protein,LMP)在子宫颈病变组织中的mRNA和蛋白表达,探讨其与HPV16感染的关系。方法以152例新疆维吾尔族妇女正常子宫颈上皮、子宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)和子宫颈鳞癌(cervical squamous cell carcinoma,CSCC)患者为研究对象,采用RT-PCR和免疫组化法鉴定LMP2和LMP7mRNA及蛋白表达水平;采用PCR技术检测相应标本HPV16感染情况。结果 (1)LMP2、LMP7随着子宫颈病变的加重其蛋白表达逐渐降低,且mRNA表达水平与蛋白表达趋势相一致。在CIN中LMP2、LMP7蛋白表达下调和缺失率分别为25.0%/15.6%、29.7%/23.4%;在子宫颈癌中LMP2、LMP7蛋白的表达下调和缺失率分别为17.5%/34.9%、23.8%/41.3%。临床病理参数进行分析发现LMP2、LMP7与子宫颈癌分化程度及淋巴结转移密切相关(P<0.05)。(2)PCR结果显示,HPV16的检出率随着子宫颈病变的进展而增加,在慢性子宫颈炎、CIN和子宫颈癌组织中阳性率分别为8%(2/25)、67.2%(43/64)和77.8%(49/63),且随着肿瘤恶性程度的增加其阳性表达率增加,各组间阳性表达差异有统计学意义(P<0.05)。在CIN中LMP7表达下调与HPV16感染有关(P<0.05),子宫颈癌中LMP2和LMP7表达下调与HPV16感染有关(P<0.05)。结论 LMP基因的转录表达下调或蛋白质表达缺失与维吾尔族妇女子宫颈癌病变进程密切相关,其中HPV16感染可能是重要原因之一。