Comparison of the detection of cervical human papillomavirus infection by filter DNA hybridization of cytologic specimens and by in situ DNA hybridization of tissues

Cellular samples and subsequent cone biopsy samples from the same site in 18 patients were screened for infection with human papillomavirus (HPV) types 16 and 18 (HPV 16/18) by DNA hybridization. Filter hybridization of cells collected using cervical swabs was significantly less sensitive (with only 4 positive results) in detecting HPV 16/18 DNA sequences than was in situ hybridization of tissue sections (with 16 positive results). The in situ hybridization results correlated well with the cytologic and histologic findings of cervical intraepithelial neoplasia of grades II (mild dysplasia) and III (severe dysplasia and carcinoma in situ).     

Prevalence of Chlamydia trachomatis and oncogenic human papillomavirus types in cytologic atypia of the uterine cervix

A history of having substantial Chlamydia trachomatis exposure as detected by serum antibodies is a cofactor of human papillomavirus (HPV) mediated cervical carcinogenesis. In this study, we examined the concurrent C. trachomatis infections in cytologic atypia of the uterine cervix in order to evaluate the impact of C. trachomatis infection in patients with high risk for cervical intraepithelial neoplasia. Cervical scrapes form 707 patients were subjected to PCR amplification with primer sets for HPV and C. trachomatis. Based on negative beta-globin results, 10 specimens were not eligible for further analysis. Oncogenic HPV types were detected in 278 specimens (39.8%). C. trachomatis was found only in six specimens (0.9%). In conclusion, concurrent C. trachomatis infection was uncommon and hence it was an improbable risk factor in cytologic atypia.     

A prospective study of human papillomavirus infection of the cervix

In a prospective study 42 women, diagnosed as having low grade cervical intraepithelial neoplasia (CIN), made a total of 281 clinic visits over a 45 month period. At each visit, they were subjected to cytological and colposcopical examination and samples were taken for human papillomavirus (HPV) DNA hybridization studies and for the detection of non-HPV infections. HPV types 16 and/or 18 were found in 25% of all the samples tested and these virus types were detected in five of six (83%) women whose lesions progressed compared to seven of 14 (50%) of those whose lesions regressed. The presence of HPV DNA was not a good prognostic indicator of progression since half of those whose disease regressed also harboured these viruses at some time. The recording of non-HPV infections almost 10 times more often in the women whose disease regressed than in those whose disease progressed could probably be accounted for by the former having a larger number of follow-up visits. Nevertheless, the significance of non-HPV infections also remains unclear.     

Control of interferon signaling in human papillomavirus infection

Human papillomaviruses (HPV) infect mucosal and cutaneous epithelium resulting in several types of pathologies, most notably, cervical cancer. Persistent infection with sexually transmitted oncogenic HPV types represents the major risk factor for the development of cervical cancer. The development of HPV-associated cervical cancer has been closely linked to the expression of the viral oncogenes E6 and E7 in the tumor cells. The major viral oncoproteins, E6 and E7, target the cellular tumor suppressor gene products p53 and Rb, respectively. As detailed within, these interactions result in the stimulation of proliferation and the inhibition of apoptosis, thus representing major oncogenic insults to the infected cell. In addition to mediating transformation, the E6 and E7 genes also play significant roles in altering the immune response against infected cells by suppressing interferon (IFN) expression and signaling. At the clinical level, IFNs have been used in the treatment of HPV-associated cervical intraepithelial neoplasia (CIN) or cervical cancers with mixed results. The success of the treatment is largely dependent on the subtype of HPV and the immune response of the patients. Despite this inefficiency, the increasing knowledge about the regulation of IFN signaling pathways at molecular level may hold a promise for the use of new therapeutic strategies against HPV infection. Studies on the regulation of the function of IFN-inducible gene products by the E6 and E7 may lead to the development of new therapeutic approaches based on strategies that modify the function of the HPV oncoproteins and restore IFN-signaling pathways through endogenous control mechanisms.     

人乳头瘤病毒（HPV）感染与阴道微生态的相关性研究

目的 探讨人乳头瘤病毒（HPV）与阴道微生态的相关性。为阴道微生态失衡患者及时纠正阴道菌群的紊乱,避免或减少其感染HPV及宫颈癌的防治提供科学依据。方法 选取2015年5月－2016年6月在我院妇科门诊就诊的1412例患者进行HPV、阴道微生态检测。分析阴道菌群及微生态结果与HPV感染的相关性。结果 1412例患者中HPV阳性有542例,占38.39%,HPV阴性有870例,占61.61%。分别以革兰阳性大杆菌、革兰阴性短杆菌、革兰阳性杆菌、革兰阳性球菌/链球菌为优势菌及无优势菌的患者,HPV感染率分别为34.45%、49.16%、33.33%、39.28%、38.70%,OR值分别为0.654（0.526-0.815）、1.818（1.426-2.318）、1.426（0.515-1.209）、1.039（0.483-2.236）、1.014（0.601-1.711）。细菌性阴道病（BV）、滴虫性阴道炎（TV）、需氧性阴道炎（AV）、外阴阴道假丝酵母菌病（VVC）的HPV感染阳性率分别为27.49%、1.29%、7.38%、12.54%,P值分别为0.000、0.754、0.570、0.318。结论 HPV感染与革兰阴性短杆菌及BV显著相关,革兰阳性大杆菌与HPV的感染呈负相关,菌群紊乱及BV可能增加HPV感染的风险。     

人乳头瘤病毒感染与宫颈癌的研究进展

人乳头瘤病毒(Human Papillomavirus HPV)感染是导致性传播疾病的常见原因,上世纪八十年代初,首次报道生殖器HPV感染与宫颈癌之间的联系,认为HPV感染是95%以上宫颈癌变的高危因素。随着分子生物学技术的发展,对HPV致癌机制的研究不断深入,取得大量有价值的成果,现就HPV的致癌途径与协同因素探讨宫颈癌的发病机制以及对HPV检测方法等方面的研究进行综述。     

Genital human papillomavirus infection in women from the Zagreb region

Human papillomavirus (HPV) infection is the most common sexually transmitted infection, especially among young, sexually active individuals. As persistent infection with oncogenic types may lead to cervical cancer, HPV testing is a useful tool to screen for women at risk for subsequent development of cervical cancer. The aim of the study was to determine the prevalence of high-risk HPV (hrHPV) infection in different age groups of cytologically selected women from the Zagreb region, and to evaluate the frequency and results of repeat hrHPV testing. During a one-year study period (November 2005 to November 2006), a total of 3,440 cervical samples from women attending gynecological services of public and private health care systems were received. They were tested for 13 hrHPV genotypes by the polymerase chain reaction based AMPLICOR HPV test (Roche Molecular Systems). The overall prevalence of hrHPV was 34.6%. Most samples were obtained from women aged 21-30 years (44.2%), followed by the 31-40 (27.6%), 41-50 (15.7%), 51-60 (5.3%) and 261 (2.4%) age groups. Out of 3,227 cervical samples obtained from women of known age, 4.9% were obtained from the group of girls younger than 21, in which the highest prevalence of hrHPV (49.4%) was found. A similar prevalence was observed in women aged 21-30 (45.1%). The prevalence gradually decreased with age. During the study period, repeat hrHPV testing was performed in samples from 66 women at different intervals. Out of 28 women that were hrHPV negative on initial testing, only five women turned positive on repeat testing. Out of 38 women that were positive on initial testing, in one-third hrHPV could not be detected on repeat testing. As expected, hrHPV infection was highly prevalent in female adolescents and young women. Further investigation on repeat hrHPV testing is needed to assess virus clearance and rate of newly acquired infection.     

Strategies against human papillomavirus infection and cervical cancer

Papillomaviruses infect a wide variety of animals, including humans. The human papillomavirus (HPV), in particular, is one of the most common causes of sexually transmitted disease. More than 200 types of HPV have been identified by DNA sequence data, and 85 HPV genotypes have been well characterized to date. HPV can infect the basal epithelial cells of the skin or inner tissue linings, and are, accordingly, categorized as either cutaneous or mucosal type. HPV is associated with a panoply of clinical conditions, ranging from innocuous lesions to cervical cancer. In the early 1980s, studies first reported a link between cervical cancer and genital HPV infection. Genital HPV infections are now recognized to be a major risk factor in at least 95% of cervical cancers. 30 different HPV genotypes have been identified as causative of sexually transmitted diseases, most of which induce lesions in the cervix, vagina, vulva, penis, and anus, as the result of sexual contact. There is also direct evidence demonstrating that at least four of these genotypes are prerequisite factors in cervical cancer. The main aim of this review was to evaluate the current literature regarding the pathovirology, diagnostics, vaccines, therapy, risk groups, and further therapeutic directions for HPV infections. In addition, we reviewed the current status of HPV infections in South Korean women, as evidenced by our data.     

Identification of the dynein light chains required for human papillomavirus infection

Human papillomaviruses (HPVs) are a family of small non-enveloped DNA viruses. Some genital HPV types, including HPV type 16 (HPV16), are the causative agent for the development of cancer at the site of infection. HPVs encode two capsid proteins, L1 and L2. After endocytic cell entry and egress from endosomes, L2 accompanies the viral DNA to the nucleus where replication is initiated. For cytoplasmic transport, L2 interacts with the microtubule network via the motor protein complex dynein. We have performed yeast two-hybrid screening and identified the dynein light chain DYNLT1 (previously called Tctex1) as interaction partner of HPV16 L2. Using co-immunoprecipitation and immunofluorescence colocalization studies we confirmed the L2-DYNLT1 interaction in mammalian cells. Further studies revealed that DYNLT3, the second member of the Tctex-light chain family, also interacts with L2 in vitro and in vivo, whereas other constituents of the dynein complex were not found to associate with L2. Depletion of DYNLT1 and DYNLT3 by specific siRNAs or cytosolic delivery of light chain-specific antibodies inhibited infection of HPV16. Therefore, this work identified two host cell proteins involved in HPV16 infection that are most likely required for transport purposes towards the nucleus.     

The cytologic identification and quantification of testicular cell subtypes. Reproducibility and relation to histologic findings in the diagnosis of male infertility

In testicular imprint smears from 100 infertile men (both testicles), stained using the Pappenheim and Papanicolaou methods, the cell forms (light and dark spermatogonia, primary and secondary spermatocytes, spermatids, spermatozoa and Sertoli cells) were identified and quantified by the counting of 500 consecutive cells. Identification of the cell types, which are described and illustrated, was consistent and reproducible; the advantages of the different stainings in their analysis is documented. The cell counts were tested for reproducibility and compared to the histologic diagnoses and sperm counts. Statistical analysis showed the highest reproducibility for cells frequently encountered in smears (0.99 for Sertoli cells and 0.98 for spermatozoa) and the lowest but still satisfactory reproducibility for rare or arbitrarily defined cell forms (0.71 for dark spermatogonia and 0.76 for secondary spermatocytes). The high reproducibility of the smear quantification permits the introduction of a number of indices, defining clinically useful relations between cell types that are indicative of various types of infertility. The data obtained by cytologic quantification showed reasonably good correlation with the histologic diagnoses of desquamation and focal fibrosis and excellent correlation with Sertoli cells only, arrested spermatogenesis and complete fibrosis. The cytologic quantification of testicular smears adds considerable information to the diagnosis of impaired fertility and should be instituted in properly equipped centers.     

人乳头瘤病毒感染与肿瘤的相关性研究进展

人乳头瘤病毒(Human papillomavirus,HPVs)是一种嗜人体皮肤和黏膜的DNA病毒,约80%有性行为的女性可能感染HPV。宫颈癌是最常见的恶性肿瘤之一,是女性肿瘤中仅次于乳腺癌的第二个常见的恶性肿瘤,高危型HPV感染是其主要致病因素,则宫颈癌是目前唯一病因明确的妇科恶性肿瘤。HPV感染亦与其他恶性肿瘤的发生、发展密切相关,可引起除宫颈癌外的其他泌尿生殖道肿瘤,以及消化道系统、呼吸道系统、眼科、皮肤等其他系统或器官肿瘤。对HPV感染所致肿瘤的相关研究进展进行了综述,为肿瘤病因和发生机理的研究提供了新的思路。     

Genital human papillomavirus testing by in situ hybridization in liquid atypical cytologic materials and follow-up biopsies

OBJECTIVE: To describe cases of HPV testing by DNA in situ hybridization performed on atypical cervicovaginal samples collected by a liquidsed method that were negative for HPV DNA on cytology but revealed cervical intraepithelial neoplasia on follow-up biopsies. STUDY DESIGN: Three hundred ninety-five consecutive SurePath atypical squamous cells of undetermined significance (ASC-US) cytologic samples from asymptomatic, reproductive-age women were tested for human papillomaviruses (HPVs) by the in situ hybridization (ISH) method (Ventana Inform HPV Test, Tucson, Arizona, U.S.A). One hundred (25%) cases underwent follow-up colposcopic biopsy within 3 months of cytology. All the tests (cytology, ISH, histology) were independently evaluated without knowledge of the other tests. RESULTS: One hundred twenty-two (33%) cytologic samples were positive for HPVs. Of a total of 100 (HPV positive and negative) follow-up biopsies, 55 were positive for cervical intraepithelial neoplasia (CIN). Fourteen cases of biopsy-proven CIN tested negative for all HPV types in the prior cytologic samples. Retesting of the 14 CIN tissues by ISH was negative in 10, positive for HPV in 2 and inconclusive in 2. CONCLUSION: There is a small but significant (14%) false negative rate with HPV testing by the Ventana ISH method. Clinically suspicious cases should be followed even if an HPV test is negative.     

Persistence of human papillomavirus infection: keys to malignant progression

Human papillomaviruses (HPVs) are the etiologic agents of cervical and other epithelial cancers. Persistence of infections by high-risk HPV types is the single greatest risk factor for malignant progression. Although prophylactic vaccines have been developed that target high-risk HPV types, there is a continuing need to understand better the virus-host interactions that underlie persistent benign infection and progression to cancer. In this review we summarize the molecular events that facilitate the differentiation-dependent HPV life cycle, how the life cycle is organized to facilitate virus persistence, and how the activities of HPV regulatory proteins result in malignancy.