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Background: In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies., Methods: A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies., Results: A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7); 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling; 95% CI, 0.75-0.88; P < .0001) and non-virus-related epithelial non-AIDS-defining malignancies (IRR, 0.84; 95% CI, 0.75-0.95; P = .004), but not with other non-AIDS-defining malignancies (IRR, 1.04; 95% CI, 0.83-1.31; P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86; 95% CI, 0.75-0.99; P = .03), Hodgkin lymphoma (n = 52; IRR, 0.83; 95% CI, 0.73-0.95; P = .005), and lung cancer (IRR, 0.76; 95% CI, 0.64-0.90; P = .0002)., Conclusions: A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed., (Copyright © 2010 American Cancer Society.)

BK polyomavirus (BKV) is essentially ubiquitous in all human populations worldwide. Asymptomatic infection with this virus occurs during early childhood, leading to life-long persistence in the kidney. BKV has four subtypes that can be identified using serological and genotyping methods. The evolutionary aspects of BKV have remained poorly understood due to the limited availability of BKV genomes, since urinary excretion of BKV DNA is detected primarily in immunocompromised individuals. However, we have found that BKV DNA sequences can often be amplified from non-immunocompromised elderly individuals, using a highly sensitive polymerase chain reaction (PCR) with highly concentrated urinary DNA as the source of viral DNA. Using this approach, we have PCR-amplified and sequenced a large number of partial and complete BKV genomes from various human populations worldwide and conducted a series of evolutionary studies using these sequences. We have shown that subtypes I and IV evolved into four and six subgroups, respectively, with each having a close relationship with a particular human population. In addition, we have provided evidence supporting the hypothesis that BKV strains with the archetypal transcriptional control region (TCR) circulate in the human population. In this review, we describe these findings and discuss their epidemiological, anthropological and clinical implications.

The trends in head and neck cancer incidence and smoking prevalence are reviewed, discussing where such trends parallel but also how and why they may not. In the U.S., public health efforts at tobacco control and education have successfully reduced the prevalence of cigarette smoking, resulting in a lower incidence of head and neck cancer. Vigilance at preventing tobacco use and encouraging cessation should continue, and expanded efforts should target particular ethnic and socioeconomic groups. However, an unfortunate stagnation has been observed in oropharyngeal cancer incidence and likely reflects a rising attribution of this disease to oncogenic human papillomavirus, in particular type 16 (HPV-16). For the foreseeable future, this trend in oropharyngeal cancer incidence may continue, but with time the effects of vaccination of the adolescent and young adult female population should result in a lower viral prevalence and hopefully a reduced incidence of oropharyngeal cancer. To hasten the reduction of HPV-16 prevalence in the population, widespread vaccination of adolescent and young adult males should also be considered.

Background: Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) has a high predictive value for high-grade intraepithelial lesion (HSIL) in the general population. However, the significance of ASC-H in pregnant women remains to be elucidated. The objective of this study was to investigate the clinical implications and pathologic significance of ASC-H in pregnant women, so that these patients will be managed appropriately., Methods: All Papanicolaou tests that were diagnosed as ASC-H in pregnant women over 1.5 years (total, 60 women) were reviewed and correlated with histologic and/or cytologic follow-up. High-risk type of human papillomavirus (HPV) status was also correlated with follow-up findings. The following cytomorphologic parameters were evaluated for each woman and were compared between the squamous intraepithelial lesion (SIL) follow-up group and the benign follow-up group: inflammatory background, the number of atypical cells, cell arrangement pattern, nuclear irregularity/grooves, hyperchromasia, and cell shape., Results: Among 30 women who had histologic follow-up, 3 women (10%) had HSIL, and 13 women (43%) had low-grade intraepithelial lesion (LSIL). Among 32 women who had cytologic follow-up, 2 women (6%) had HSIL, 3 women (9%) had LSIL, 1 woman (3%) had ASC-H, and 3 women (9%) had atypical squamous cells of undetermined significance (ASCUS). HPV was detected in 24 of 43 women (56%). The cytomorphologic features were similar in the SIL follow-up group and the benign follow-up group. No specific cytomorphologic features that predicted underlying SIL were identified., Conclusions: ASC-H in pregnant women had a lower predictive value for an underlying HSIL compared with the general population. A positive HPV test result was not a good indicator for an underlying SIL, but a negative result appeared to be useful for ruling out an underlying HSIL. Because of low positive predictive value for HSIL and the difficult colposcopic examination, a more conservative follow-up may be reasonable for pregnant women who have a diagnosis of ASC-H. HPV testing may be used as an adjunctive test., ((c) 2006 American Cancer Society.)

The seroprevalence of feline immunodeficiency virus (FIV) in 203 apparently healthy domestic cats living in the district of Pisa, central Italy, was 11.3 per cent, and the prevalence of feline leukaemia virus (FeLV) was 8.4 per cent. The prevalence of FIV depended significantly on the lifestyle and age of the cats; cats living outdoors were more likely to be FIV-positive than cats living indoors, and the proportion of FIV-positive cats increased with age. In contrast, there was no significant relationship between these variables and the prevalence of FeLV. There was no significant relationship between the cats' seropositivity for FIV and FeLV. The results of a five-year field study to control FeLV infection by vaccination in a colony of 30 domestic adult cats naturally exposed to the infection suggest that the vaccination was effective in FIV-negative cats, but failed to protect FIV-positive cats against FeLV.

Bovine herpesvirus type 4 (BHV-4), a member of the genus Rhadinovirus, subfamily Gammaherpesvirinae, within the family Herpesviridae, was isolated in fetal bovine lung cells from samples of vaginal discharge taken from a dairy herd in which approximately 50 per cent of the cattle developed metritis after calving. The identity of the isolate was confirmed by immunofluorescent staining with a BHV-4-specific monoclonal antibody and partial sequencing of a portion of the glycoprotein B gene. Serological testing failed to demonstrate a significant association between the exposure of the cattle to BHV-4 and the metritis, but several cattle seroconverted during the periparturient period, consistent with the recrudescence and shedding of virus associated with the stresses of parturition and the onset of lactation. Despite the previous failure to detect BHV-4 in Northern Ireland, a serological survey of 999 cattle in 49 dairy herds and 51 beef herds found widespread evidence of exposure: 29 of the dairy herds and 35 of the beef herds contained one or more seropositive cattle, and 33.3 per cent of the dairy cattle and 23.3 per cent of the beef cattle were positive.

Objective: Persistence of human papillomavirus (HPV) is associated with an increased risk of developing cervical SIL and cancer in young women. Because this association in older, postmenopausal age women has received little attention, we evaluated persistence of HPV among women in this age group., Methods: Women (n=105) ages 45-64 were examined annually for 7 years to evaluate HPV in cervical cytologic specimens. PCR, dot blot hybridization and DNA sequencing were used to detect HPV types., Results: The cumulative prevalence of HPV was 34%, and 24% had HPV high-risk oncogenic types which are associated with genital cancers. The most common oncogenic types were HPV-16 (72%) and HPV-31 (16%). The persistence rate of HPV infection was 16%. No specific risk factors were associated with repeat viral positivity., Conclusion: Postmenopausal women are infected with persistent oncogenic HPV at a substantial rate, supporting the need for continued screening in postmenopausal women to detect preneoplastic genital lesions.

The potential for human papillomavirus (HPV) DNA testing in cervical cancer prevention programs has been a topic at the forefront of cervical cancer policy discussions in recent years. To prevent some of the anxiety and psychological distress often experienced on HPV diagnosis and during the period of management, mass patient education must accompany the incorporation of HPV DNA testing into screening protocols. To contribute to a growing body of work that provides an empiric basis for development of effective counseling messages about HPV and HPV testing, this paper highlights women's most common information gaps and psychosocial concerns and describes the different perspectives offered by women's usual sources of information about HPV, including the crucial role of the clinical community in creating a shared decision making environment in which screening decisions and results can be discussed.

Serum antibodies are widely utilised as specific and sensitive markers of virus infections but they have been employed relatively infrequently in the investigation of simian virus 40 (SV40) as a human carcinogen. In the past few years, serological data have become available which allow an examination of whether SV40 is currently circulating in human communities and if SV40 infection is associated with human cancer. The development of EIA with virus-like particles (VLPs) of SV40, BKV and JCV has facilitated serological studies. Sera from macaques naturally infected with SV40 cross-react unambiguously with BKV and JCV VLPs. Tests of over 9000 human sera with different immunological assays reveal a common pattern of SV40 reactivity. A small proportion of sera react at low titers and this reactivity is unrelated to age or the geographic location of the donor, but correlates with the presence and titers of BKV and JCV antibodies. Absorption with BKV and JCV VLPs decreases or abolishes the SV40 reactivity of human sera. The SV40 reactivity of sera from patients with mesothelioma, osteosarcoma or lymphomas, cancers which are reported to be associated with SV40, was similar to that in their controls or other comparison groups. The SV40 reactivity of human sera appears to be almost entirely a result of cross-reactivity with BKV and JCV antibodies. Serological data thus do not support the possibility that SV40 is circulating in human communities or that it is associated with human cancer., (Copyright 2004 John Wiley & Sons, Ltd.)

A small DNA virus, named JC virus (JCV) and belonging to the Polyomaviridae, is attracting the attention of anthropologists worldwide, as JCV genotyping appears to be a novel means of elucidating human migrations and the origins of various ethnic groups. The basic properties of JCV, the regional distributions of JCV genotypes, and the phylogenetic relationships among various JCV genotypes are described. Then, a study is described in which the origin of the modern Japanese was extensively investigated using the JCV genotyping method. Based on JCV genotypes in neighboring areas, the origins of people who carried JCV genotypes to the Japanese Archipelago are discussed. Finally, the relationships between JCV genotypes and Y-chromosome haplogroups are examined, as genetic variation on the Y chromosome has recently been examined in detail to investigate ancient human migrations and the population structures of human groups., (Copyright 2004 John Wiley & Sons, Ltd.)

Polyomavirus BK has emerged as an important cause of renal allograft infection leading to allograft dysfunction and loss in kidney transplant recipients. Significant progress has been made, particularly in the area of diagnostic methods for BK virus, thereby facilitating diagnosis, screening and monitoring of infection. This review outlines current concepts on the epidemiology, pathogenesis, diagnosis and therapy of BK virus nephropathy. The precise risk factors that are important for induction and progression of infection to invasive disease, the most effective diagnostic strategies, and the efficacy of current therapeutic approaches, all remain to be defined fully. It is to be hoped that these deficiencies will stimulate research to address these important questions., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Effective screening programs have contributed to a decrease in the incidence of cervical squamous cell carcinomas but have had a limited sensitivity in the detection of adenocarcinoma precursor lesions. The aim of our study was to analyze cervical adenocarcinoma in greater detail: symptoms preceding the detection, the method of detection and the prevalence of human papillomavirus (HPV) with respect to age at diagnosis., Material and Methods: Clinical data were abstracted from the medical records of 82 women with pure invasive cervical adenocarcinomas. As diagnostic tools we used polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) and/or direct DNA sequencing for HPV detection., Results: Age at diagnosis predicting factors were HPV status, positive lymph nodes, histology and stage. HPV-negativity, lymph node metastases, advanced stage and poor differentiation were all associated with a high diagnostic age. In the multivariate analysis only HPV status was shown to have an independent impact on age at diagnosis, while stage showed only borderline significance. Twenty-three percent of the cancers were detected by screening and the remaining were due to different symptoms. Among the women considered, 93% had a normal Papanicolaou (Pap) smear 3 years before diagnosis and 60% within 1 year. There was no significant correlation between smoking, oral contraceptives and HPV-positivity., Conclusions: The absence of HPV was significantly associated with a high age at diagnosis. Pap screening had a limited effect in detecting adenocarcinoma at an early stage.

Background: (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting underlying cervical intraepithelial neoplasia., Materials and Methods: In this prospective cohort, 148 women with atypical squamous or glandular cells of undetermined significance were evaluated by colposcopy, histological sampling, and human papillomavirus deoxyribonucleic acid testing., Results: Histological diagnosis of >/= cervical intraepithelial neoplasia II was found in 10/148 women. Women with a histological >/= cervical intraepithelial neoplasia II had a higher prevalence of >/= two abnormal quadrants (90% vs. 38%/= cervical intraepithelial neoplasia II.

Background: Cervical cancer affects 1 in 2000 Zimbabwean women. We investigated the type-specific distribution of human papillomavirus (HPV) infection in Zimbabwean women with invasive cervical cancer., Methods: We conducted a descriptive study on 98 women with invasive cervical cancer. The methods used were a nested polymerase chain reaction (PCR) for amplification of HPV-DNA and restriction fragment length polymorphism (RFLP) to characterize the HPV types., Results: HPV-DNA was identified in 97% of the cases. HPV types 16, 33, 18 and 31 were identified in 61%, 39%, 18% and 4% of the patients, respectively. We typed one case each of HPV types 35 and 58. Multiple HPV infections were present in 24%. All patients (n = 3) with adenocarcinoma of the cervix were infected with the HPV. Patients infected with HPV-16 alone presented at a median age of 46 years while those infected with HPV-33 alone presented at 43 years. However, patients coinfected with both HPV-16 and HPV-33 were between 10 and 13 years older (median age of 56 years) than patients with either HPV-16 or HPV-33 as single infections. These differences were marginally significant (p = 0.08) or significant (p = 0.02), respectively., Conclusion: We present the first prevalence data on HPV types in patients with cervical cancer in Zimbabwe and show that, provided appropriate techniques are employed, HPV infection can be identified in a majority of the patients. The distribution of HPV types should be taken into consideration in tailoring locally relevant vaccines against HPV.

Human papilloma virus (HPV) can reach a child's anogenital area by vertical transmission or by close contact, which can be either sexual or nonsexual. Our objective was to compare HPV in prepubertal girls with and without lichen sclerosus (LS). We compared the frequencies and types of HPV in girls with LS with those in children with non-LS vulval disease (vulval swab and urine) and in children with no known vulval disease (urine only). HPV DNA was detected using a nested polymerase chain reaction (PCR) with general and consensus primers amplifying a region of the L1 gene, and PCR amplicons were typed using reverse hybridization with labeled HPV type-specific probes. Specimens untypeable by this method were typed by DNA sequencing. In the cohort of children with LS, we recorded the presence of maternal anogenital warts or a dysplastic cervical smear within 3 years of the affected child's birth. We found that HPV was present in the urine and vulval swabs of 8 of 32 children with LS and in 2 of 31 children with non-LS vulval disease, but also in the urine of 7 of 29 controls. In those with LS, the frequency was not increased significantly, but the types were predominantly those commonly associated with dysplasia of the cervix, penis, vulva, and anus, as opposed to the broader spectrum of types found in the control group, not all dysplasia associated. Two of the 32 mothers reported warts, and 15 of 32 (46.9%) had an abnormal smear. (The national average of abnormal cervical smears is less than 10%.) We concluded that HPV appears to be common in all prepubertal girls, but children with LS carried types associated with dysplasia and their mothers had had a high incidence of dyskaryotic smears.

Background: Lung cancer is the leading cause of cancer death in Taiwan, and the paucity of dependable risk markers has impeded the early management of lung cancer. An association of human papillomavirus (HPV) 16/18 infection with lung cancer among nonsmoking Taiwanese women was revealed in our previous study., Methods: Nested PCR was employed to detect HPV 16/18 DNA in the blood circulation of 149 lung cancer patients and 174 noncancer controls. In addition, correlation of prevalence of HPV DNA between the blood circulation and lung tumor tissue was compared from 70 sets of paired tumor tissues and peripheral blood samples available., Results: The results showed that the prevalence rate of HPV 16/18 in the blood circulation of lung cancer cases was significantly higher than that of noncancer controls (47.7% vs. 12.6% for HPV 16, P < 0.0001; 30.9% vs. 5.2% for HPV 18, P < 0.0001). A significantly higher HPV 16 prevalence was detected in female lung cancer patients than that of male (57.6% vs. 41.1%, P = 0.048), as well as in cases with tumor Stages III/IV than those with tumor Stages I/II (54.6% vs. 29.3%, P = 0.006). After adjusting the effects of age, gender, and smoking status, a 6.5-fold greater risk of lung cancer was demonstrated for those subjects with HPV Type 16 positive (95% CI 3.7-11.3, P < 0.0001), a 9.2-fold for HPV Type 18 positive (95% CI 4.2-20.2, P < 0.0001), and a 75.7-fold greatest risk for those with both HPV Type 16 and 18 positive (95% CI 9.8-582.1, P < 0.0001)., Conclusions: These results suggested that the presence of HPV DNA in the blood circulation may serve as a feasible risk marker of lung cancer., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11191)

Background: Infertile women in Sweden are offered in vitro fertilization (IVF) within the frame of the social security system. The present investigation was undertaken to evaluate the prevalence of genital human papilloma virus (HPV) infection in relation to the results of cytologic screening and to the infertility in these women., Material and Methods: Two hundred and fourteen women, mean age 32 years (range 20-40), admitted to the Center for Reproduction at Uppsala University Hospital for investigation of infertility and IVF were studied. Human papilloma virus tests were performed by a sensitive polymerase chain reaction-based technique in cervical smears obtained at a medical examination or during oocyte retrieval. Cytologic screening results were obtained from medical records or at the time of investigation. The infertile women were compared with 197 healthy female controls., Results: Infertility resulted from female factors in 47% and male factors in 29% of the cases, and remained unexplained in 24%. Seven percent of the infertile women were HPV-positive compared with 9.1% of the controls. Only genital and oncogenic HPV types were identified. Human papilloma virus type 16 was most prevalent, and examination of the HPV 16 E6 gene showed that this prototype predominated over variants. No correlation was found between HPV infection and cause of infertility. Abnormal cytology was observed in 2.3% of the infertile women and 4.1% of the controls., Conclusions: Human papilloma virus infections might appear somewhat less frequently in infertile women admitted for IVF than in a control population. In both groups HPV infection was more common than cytologic abnormalities, possibly indicating that present HPV tests are more sensitive in detecting HPV infections than cytologic screening.

Background: Oncogenic human papillomaviruses (HPV) DNA have repeatedly been observed in many head and neck carcinomas (HNSCCs), and HPV infections are currently considered a possible factor in the etiology of these tumors. However, the reported prevalences of HPV-DNA in HNSCC are variable. In the current study the authors used highly sensitive polymerase chain reactions (PCRs) to analyze the occurrence of viral sequences in 98 carefully stratified HNSCCs. The authors determined the load and localization of HPV DNA in a subset of tonsillar carcinomas and their metastases., Methods: Nested PCR and an HPV16 specific single step PCR were used to screen 98 HNSCCs for HPV DNA for genital- and Epidermodysplasia verruciformis (EV)-associated HPVs. Typing was performed by direct sequencing and/or sequencing of cloned amplimers. In two patients HPV16 subtypes in tonsillar carcinomas and their metastases were compared by amplification and sequencing of the long control region of the virus. In a subset of HPV16 positive tonsillar carcinomas and their metastases, localization and viral load were determined using laser assisted microdissection and real time fluorescent PCR, respectively., Results: Altogether 25 HNSCCs (26%) were found to be HPV positive. Stratified according to the tumor localization, the frequency of HPV positive lesions was 18% in the oral cavity, 45% for oropharynx, 25% for hypopharynx, 8% for nasopharynx, and 7% for larynx. The highest HPV DNA prevalence (58%) was found in tonsillar carcinomas. The high risk HPV type 16 was found in 84% of positive HNSCCs, in 14% of which EV-associated HPVs were detected. Human papillomavirus sequences were detected in 64% of biopsies with normal mucosa from 11 patients with positive carcinomas. As a control group, 14 tumor free tonsils were analyzed. In none of these specimens were HPV sequences detected. Viral long transcriptional control region sequences in homologous metastases were identical with those in primary tumors and the load values in both locations were roughly comparable. Viral loads differed substantially in different areas of one tumor. Statistical evaluation of data related to clinicopathologic parameters showed a significant linkage of HPV with tonsillar carcinomas compared to other locations. Furthermore, a significant correlation of HPV status of tonsillar carcinomas with tumor grading and alcohol consumption was found., Conclusions: Our study shows a preferential association of HPV-DNA with tonsillar carcinomas. The data support the view of HPV negative and positive tonsillar carcinomas being different tumor entities and conventional cancer risk factors being of less importance in HPV-infected individuals. The HPV genome is located in the cancer cells, whereas the infection of normal mucosa is a rare event. Data on quantification of HPV16 in tonsillar tumors and their metastases showed mean viral loads comparable to other HPV associated malignancies., (Copyright 2001 American Cancer Society.)

Objective: To determine whether human papillomavirus (HPV) type 16 affects survival in oral squamous cell carcinoma., Study Design: Two hundred fifty-four patients diagnosed with primary oral cancer were studied for survival in relation to tumor HPV type 16 status. Kaplan-Meier analysis and Cox proportional hazard models were used to assess survival and estimate hazard ratios adjusted for potential confounders., Results: HPV type 16 DNA was detected in 15.1% of tumors. HPV 16 positive patients had significantly reduced all-cause mortality (hazard ratio [HR] estimates = 0.34, 95% CI = 0.14, 0.83) and disease-specific mortality (HR = 0.17, 95% CI = 0.04, 0.76) compared with HPV 16 negative patients after adjustment for age, stage, treatment, smoking, alcohol, education, and comorbid disease., Conclusions: The presence of HPV type 16 DNA is independently associated with a favorable prognosis in patients with oral squamous cell carcinoma., Clinical Significance: Although HPV genotyping is currently not widely available, it may provide important prognostic information.

Unlabelled: The city of Recife, northeastern Brazil, is reported to have the highest incidence of cervical cancer worldwide (83.2/100000 women)., Objective: To evaluate the efficacy of Hybrid Capture I (HC I) in cervical cancer detection and some risk factors in Recife., Method: Cervical scrapes for HC I analysis followed by colposcopy were collected from 140 women (70 with cervical cancer and 70 with normal cervix) from three screening services in Recife., Result: HC I sensitivity and specificity were 82.9 and 41.4%, respectively. The odds ratios for cervical cancer when Gesta > or = 5 and vaginal parity > or = 4 were, respectively, 5.30 and 4.27., Conclusion: HC I is a moderately sensitive method to detect cervical cancer, but it does not seem to be useful as a primary screening tool for it's low specificity. Early pregnancy, high Gesta/Para and living in rural areas were important local risk factors.

Background: Several epidemiological investigations have shown that cigarette smoking leads to increased serum IL-6 levels and is a risk factor for cervical cancer., Methods: We examined the levels of interleukin 6 (IL-6) and the amount of cotinine in the cervical fluid of 78 women and compared the presence of human papillomavirus (HPV) in smokers and nonsmokers., Results: The results of our study showed that IL-6 levels were higher in the cervical mucus of smokers than in nonsmokers. Fourteen percent of smokers were in the category with highest IL-6 levels compared to 6% of nonsmokers. However, our IL-6 results were not significant as they were probably influenced by the higher rates of HPV infection in smokers (17 cases) than in nonsmokers (4 cases). Significant findings showed that smokers had a higher prevalence of squamous intraepithelial lesions (SILs) than nonsmokers. Smokers' cotinine levels also exceeded those of nonsmokers: 13.95 ng/ml compared with 5.00 ng/ml. However, less IL-6 activity was evident in smokers with high-grade SILs and HPV infection of high-risk types., Conclusion: Our results suggest that smoking has a stimulatory effect on the production of IL-6 in the cervix. Furthermore, smokers show a higher genital HPV infection rate and a higher prevalence of SILs.

The presence of high-risk human Papillomavirus types 16, 18 and 33 was examined in 125 pregnant patients with abnormal Papanicolau smears. Specimens of cervicovaginal cells were analyzed by a simplified method of slot-blot hybridization. The overall prevalence of those viral sequences was 48%, being: 22.4% of HPV16, 17.6% of HPV18, 4.0% for double HPV16 and 18 infestation and 4.0% of HPV33. Their prevalence in HPV positive cervical sample was alone respectively 46.6%, 36.6%, 8.3% and 8.3%. Besides the high incidence of those carcinogenic types and intense viral proliferation, a rapid progression from CIN to carcinoma was clinically observed in four pregnant patients. Our data may reinforce the idea that progesterone has a positive role to the persistence and transformation of 'high risk' HPV, particularly of HPV16. The enhanced detection of potentially malignant types during pregnancy should warn on the importance of early diagnosis and treatment of papillomatosis.

Background: To the authors' knowledge, human papillomavirus (HPV)-associated carcinomas in Hawaii have not been studied in detail., Methods: Surveillance, Epidemiology, and End Results data (from 1973-1996) were used to study rate of incidence patterns of squamous cell carcinomas (SCCs) of the uterine cervix, vulva/vagina, anus, penis, and palatine tonsils among Asian/Pacific Islanders and whites in Hawaii and among whites in the U.S. in general., Results: With the exception of invasive cervical SCC, male and female Asian/Pacific Islanders in Hawaii had considerably lower incidence rates of HPV-associated SCCs than Hawaii whites and U.S. whites. Among women, Hawaii whites and U.S. whites had rather similar rates of invasive anogenital and tonsillar SCCs, but in situ SCC of the cervix or vulva/vagina was diagnosed less often among Asian/Pacific Islanders and whites in Hawaii than among whites in the general U.S. Among men, Hawaii whites had higher rates than U.S. whites of both anal and tonsillar, but not penile, SCCs. Among Hawaiian men with anal carcinoma, 43% (15 of 35) had remained unmarried versus 3% (2 of 65) of Hawaiian women with anal carcinoma., Conclusions: Asian/Pacific Islanders in Hawaii generally have lower incidence rates of HPV-associated SCCs than whites. However, low ratios of in situ to invasive cervical SCCs suggest that many Hawaii women, notably Asian/Pacific Islanders, are not diagnosed and treated for cervical neoplasias at a preinvasive stage. The high rate of incidence of anal SCC in male Hawaiian whites and the high proportions of unmarried men among patients with this disease suggest the transmission of HPV through homosexual contact. These men may be targeted in future screening programs for anal carcinoma., (Copyright 2000 American Cancer Society.)

Objectives: To identify risk factors for human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) of the cervix, and to measure the impact of concurrent HIV-1 infection., Methods: Women were studied at a family planning clinic in Nairobi, Kenya. Demographic and historical information was obtained using a semi-structured questionnaire and specimens were collected for sexually transmitted diseases (STDs), HPV, cervical cytology, and HIV-1 testing., Results: HPV was detected in 87 of 513 women (17%), including 81 (93%) oncogenic types (16, 18, 31, 33 and others) and six (7%) non-oncogenic types (6 and 11). HIV-1 prevalence was 10%. HPV detection was associated with HIV-1 infection [adjusted odds ratio (aOR) 3.9, 95% confidence interval (CI), 2.0-7.7], sexual behavior indicators including the number of sex partners and inflammatory STDs, as well as the number of pregnancies (0 or 1 vs. > or = 3, aOR 0.4; 95% CI, 0.2-0.9). SIL was detected in 61 women (11.9%), including 28 (46%) with low-grade lesions (LSIL) and 33 (54%) with high-grade lesions (HSIL). HPV infection was strongly associated with HSIL (OR 14.9; 95% CI, 6.8-32.8). In a multivariate model predictors of HSIL included HIV-1 serpositivity (aOR 4.8; 95% CI, 1.8-12.4), the number of lifetime sex partners (0-1 vs. > or = 4; aOR 3.8; 95% CI, 1.1-13.5), and older age (< 26 vs. > 30; OR 3.9; 95% CI, 1.1-13.6). An analysis stratified by HIV-1 showed a stronger association between HPV and HSIL in HIV-1 negative women (OR 17.0; 95% CI, 6.4-46.3) then in HIV-1 positive women (OR 4.5; 95% CI, 0.8-27.4)., Conclusion: Our results indicate that HSIL and even invasive cancer are highly prevalent in this setting of women on reproductive age considered to be at low risk for STDs, suggesting that routine Pap smear screening may save lives.

Background: Some studies have shown that human papillomavirus (HPV) infection may play not only an etiologic role in anogenital cancers but also a role in the clinical outcome. The objective of the current study was to determine whether detection of HPV DNA in primary squamous cell carcinomas of the upper aerodigestive tract (UADT) is a prognostic factor in patients with the disease., Methods: The authors analyzed archival specimens of UADT tumors from 101 randomly selected patients with evaluable samples for HPV DNA detection. HPV testing was performed using a general primer-mediated polymerase chain reaction., Results: The overall detection rate was 16.8% (17 of 101 specimens). HPV DNA was detected at higher rates in specimens from younger patients and in well-differentiated tumors. Pharyngeal tumors were more likely to be HPV positive (30.0%) than buccal (10.3%) or laryngeal tumors (15.4%), but the differences were not significant. The detection rate was similar for T1-T2 tumors (17.4%) and T3-T4 tumors (15.6%). However, tumors without lymph node metastasis were more likely to be HPV positive (21.4%) than tumors with lymph node involvement (6.5%). Kaplan-Meier and Cox regression survival analyses did not show any difference in overall or disease free survival according to HPV detection., Conclusions: Although the HPV DNA detection rate was slightly higher in local than in regionally spread tumors, our results support the hypothesis that it is very unlikely that HPV detection plays any role in the prognoses of patients with UADT squamous cell carcinoma.

Objective: To determine the human papillomavirus (HPV) types in cervical adenocarcinoma of patients from Taiwan., Methods: DNA was extracted from fixed tissues and polymerase chain reaction was performed in conjunction with a unique probe, pRSA I, allowing simultaneous detection of HPV types 6, 11, 16, 18, 31 and 33 from amplified HPV DNAs after endonuclease, RsaI, digestion., Results: Of 69 tissues examined, 31.9% (22/69) were found to contain HPV DNA. Among 22 HPV-positive specimens, no HPV types 6, 11, 31 and 33 were detected. On the other hand, HPV 16 and HPV 18 were found in 11 (15.9%) and 10 (14.5%) of HPV-positive specimens, respectively. One specimen (1.5%) was found to contain both HPV 16 and 18 DNAs., Conclusions: Our findings support that HPV 18, along with HPV 16, may play a certain role in the adenocarcinoma pathogenesis of the uterine cervix.

Background: The association of Epstein-Barr virus (EBV) with Hodgkin's disease (HD) is intimately related to socioeconomic status. The proportion of HD patients with EBV is high in developing countries but low in developed countries. The aim of this study was to delineate the association of EBV with HD in Taiwan., Methods: Tissues from 70 consecutive cases of HD were examined for the presence of EBV, for the latent membrane protein (LMP- 1) by immunohistochemistry, and for EBER-1 by in situ hybridization., Results: There were 53 males and 17 females, with a mean age of 42 years (range, 7-75 years). Histologic subtypes included nodular sclerosis in 36 cases (51.4%), mixed cellularity in 26 (37.1%), lymphocyte predominance in 6, and lymphocyte depletion in 2. Overall, EBV was expressed in 44 cases (62.9%), with EBER-1 expression detected in 40 (57.1%) and LMP-1 detected in 38 (54.3%). The following histologic subtypes were associated with EBV: lymphocyte predominance in 1 of 6 cases (16.7%), nodular sclerosis in 23 of 36 cases (63.9%), mixed cellularity in 18 of 26 cases (69.2%), and lymphocyte depletion in 2 of 2 cases (100%)., Conclusions: EBV association with HD is relatively high in Taiwan. Although EBV was detected in all subtypes and at all ages in this study, the low endemic incidence of HD in Taiwan suggests that other factors, besides EBV, play a role in the pathogenesis of HD.

Objective: To evaluate the frequency of human papillomavirus (HPV) 16 and 18 infection in patients with different grades of cervical intraepithelial neoplasia (CIN)., Method: Five-hundred and five patients with CIN, referred for conization, were included in this study. Before conization, cytological material for in situ hybridization was obtained from the uterine cervix to detect the presence of HPV 16 and 18 infection., Result: Among all patients with CIN, 82 (16.2%) were solely HPV 16 and 51 (10.1%) were solely HPV 18 positive. There were 133 patients (26.3%) positive for HPV 16 or HPV 18 and 31 patients (6.1%) were positive for both viral types, giving an overall HPV 16/18 infection rate of 32.4%. There were 15 (55.5%) HPV 16 or HPV 18 positive patients with CIN 1, 45 (33.8%) HPV 16 or HPV 18 positive patients with CIN 2 and 104 (30.2%) HPV 16 or HPV 18 positive patients with CIN 3., Conclusion: In patients with CIN 1, HPV 16 and 18 infection was more frequent than in patients with CIN 2, but the difference was not significant. Patients with CIN 2 were infected slightly more frequently, but not significantly, than patients with CIN 3. On the other hand, patients with CIN 1 were significantly more frequently infected than patients with CIN 3.

Among the primates held at the CIRMF Primate Center, Gabon, no serological sign of SIV infection could be demonstrated in 68 cynomolgus monkeys, 60 chimpanzees, nine gorillas, and 12 sun-tailed monkeys, while seven of 102 mandrills and six of 24 vervets were infected with SIV. Six mandrills, seven vervets and ten cynomolgus monkeys exhibited a full HTLV type 1 Western blot profile. The sera of two gorillas and one chimpanzee presented with a positive but not typical HTLV Western blot profile. The sera of the gorillas lacked p24 antibodies, and the chimpanzee had a Western blot profile evocative of HTLV-II. All attempts to amplify viruses from these animals by PCR were unsuccessful. Two other chimpanzees and seven gorillas presented with indeterminate HTLV Western blot profiles. In the mandrill colony, only male animals were STLV seropositive and no sexual transmission to females was observed. SIV infection was also more frequent in male than female mandrills and sexual transmission appeared to be a rare event. No SRV infection was observed in macaques.

Background: Human papillomavirus (HPV) DNA has been identified in esophageal carcinomas. However, the incidence of HPV varies significantly in different geographic locations. In the current study, neoplasms from two separate geographic regions were analyzed for the presence of HPV DNA:, Methods: One hundred and ten esophageal squamous cell carcinomas, 83 from Beijing, China and 27 from Cincinnati, Ohio, were examined for the presence of HPV DNA: In situ hybridization and polymerase chain reaction (PCR) using both consensus primers for the HPV L1 gene and type specific primers for the E6 gene of HPV types 6, 16, and 18 were performed., Results: In situ hybridization failed to demonstrate any HPV type (6, 11, 16, 18, 31, 33, or 35) in any tumor specimen. Likewise, PCR using consensus primers for the HPV L1 gene was negative in all samples. Three of the Chinese specimens (4.29%) were positive for HPV using E6 type specific primers. One tumor contained HPV type 6 DNA, whereas the other 2 contained HPV type 16 DNA. One Cincinnati tumor (4.35%) was positive for HPV 16 by type specific primer. None of the specimens contained HPV 18 DNA., Conclusions: The incidence of HPV DNA in esophageal carcinoma specimens from Beijing, China and Cincinnati, Ohio is similar. The incidence of HPV in tumors from Beijing is significantly lower than that reported for those from other regions of China where the incidence of esophageal cancer is higher. Thus, although HPV may play a role in esophageal carcinogenesis, this role may be more pronounced in those regions of the world with a high incidence of the disease, and may be less important in areas with moderate or low risks for esophageal cancer.

Objective: This investigation was undertaken to assess whether pregnancy represents a risk factor for human papillomavirus (HPV) infection which is independent of age and other known HPV risk factors., Methods: One hundred eighty-nine women were enrolled from the outpatient clinics of a large municipal hospital. The subjects completed a self-administered questionnaire and underwent a gynecological examination which included a cervicovaginal lavage. Lavage samples were assessed for the presence of HPV DNA by restriction enzyme analysis and Southern blot hybridization. Statistical significance was assessed by the chi 2-test. Logistic regression was used to assess the association between pregnancy and HPV while controlling for the effect of other risk factors., Results: The prevalence odds ratio (POR) for the association of pregnancy and HPV infection was 2.2 (95% C.I. 1.1-4.5). The prevalence of HPV increased with increasing gestational age (HPV prevalence of 18.9% among non-pregnant women vs. 27.3% in those in the first 12 weeks of pregnancy and 39.7% in those who were past the 12th week of pregnancy). Although statistical significance was not achieved in a multivariate model which controlled for age, race/ethnicity, education, age at first coitus, number of sexual partners within the last year and parity, the POR associated with the current pregnancy (POR = 2.1) was not substantially changed by correcting for these risk factors, suggesting that these factors were not significant confounders of the association between pregnancy and HPV infection., Conclusion: Current pregnancy is associated with a modestly increased prevalence of cervical HPV infection. This association appears to be independent of age and other major HPV risk factors.

Background: Substantial clinical, epidemiologic, and experimental evidence has reinforced the role of high risk human papillomavirus (HPV) types in the development of cervical carcinoma. The authors investigated HPV in the uterine cervix squamous cell carcinomas and adenocarcinomas of Finnish patients., Methods: Specimens from 352 patients with uterine cervix squamous cell carcinomas and 108 with adenocarcinoma were examined for HPV DNA by polymerase chain reaction. The authors used consensus primers located in the L1 region, as well as HPV16, 18, and 33 type-specific primers located in the E6 region., Results: HPV DNA was detected in 324 of 352 squamous cell carcinomas (92%), and 81 of 108 adenocarcinomas (75%). Two-hundred seventy-four of 352 squamous cell carcinomas (78%) and 18 of 108 adenocarcinomas (17%) contained HPV16 DNA, whereas 55 of 352 squamous cell carcinomas (16%) and 60 of 108 adenocarcinomas (56%) contained HPV18 DNA. Eight squamous cell carcinomas and 4 adenocarcinomas were positive for HPV33. Twenty-eight squamous cell carcinomas and 5 adenocarcinomas were positive for either HPV16 and HPV18 or HPV16 and HPV33. Unclassified HPV DNA was detected in 17 squamous cell carcinomas and 4 adenocarcinomas. Twenty-eight squamous cell carcinomas and 9 adenocarcinomas, which were positive for E6 DNA using type-specific primers, were negative for the L1 gene. All 460 cervical specimens were tested twice with identical results., Conclusions: HPV DNA was highly prevalent in both uterine cervix squamous cell carcinoma and adenocarcinoma. HPV16 was detected more often in squamous cell carcinoma and HPV18 was detected more often in adenocarcinoma. Both consensus structural L1 gene-derived primers and type-specific viral E6 oncogene-derived primers were necessary to detect HPV DNA in cervical carcinoma.

Background: The Epstein-Barr virus (EBV) has been frequently detected in lymphoid malignancies. However, EBV infection in the nonneoplastic cells of lymphoid malignancies has not been extensively studied., Methods: Four hundred nine cases of lymphoid malignancies including 377 non-Hodgkin's lymphoma (NHL) and 32 Hodgkin's disease (HD) were examined for EBV infection by EBER-1 in situ hybridization (EBER-ISH), immunostaining against LMP-1, Epstein-Barr nuclear antigen 2 (EBNA2) and ZEBRA, and Southern hybridization using a BamHIW fragment as a probe. Double staining with EBER-ISH and immunostaining against CD20, CD45RO, and LMP-1 was performed in selected cases., Results: Although EBER-1-positive cells (EPCs) were detected in 49 of 276 B-cell lymphomas, 31 of 100 T-cell lymphomas, 1 of 1 natural killer-cell lymphoma, and 17 of 32 HDs, almost all of the tumor cells were exclusively EBER-1-positive in the 10 NHL cases. Some EPCs were of different cell lineages than the tumor cells in 15 of the 26 NHLs examined by double staining. LMP-1, EBNA2, and ZEBRA were detected in 22, 4, and 3 cases, respectively. In 4 LMP-1-positive HDs, double staining revealed that some EBER-1-positive Reed-Sternberg cells were negative for LMP-1, EBV genomic DNA was detected in 8 of the 39 examined cases., Conclusions: T-cell lymphomas contained EPCs more frequently than B-cell lymphomas. Nonneoplastic lymphocytes were infected with EBV more frequently than lymphoma cells. Rowe's latency II may be unstable in lymphoid malignancies. Some NHLs, especially T-cell lymphoma, may provide favorable conditions for EBV infection of nonneoplastic lymphocytes.

Background: The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized., Methods: We evaluated the clinical, morphologic, and immunohistochemical features of 87 patients with Hodgkin's disease and also analyzed patients for Epstein-Barr virus (EBV) using in situ hybridization for EBV DNA, RNA, and latent membrane protein (LMP1)., Results: There were 68 males and 19 females, with a mean age of 38 years. Mixed cellularity was the most prevalent subtype. Expression of EBV RNA (EBER:EBV-encoded RNA) was detected in 60 of 87 cases (69%): 1 of 1 (100%) with lymphocyte predominance, nodular; 4 of 7 (57%) with lymphocyte predominance, diffuse; 10 of 17 (59%) with nodular sclerosis; 38 of 51 (75%) with mixed cellularity; and 7 of 11 (64%) with lymphocyte depletion. Positivity was higher in advanced clinical stages; 4 of 7 patients (57%) with Stage I; 6 of 12 patients (50%) with Stage II: 7 of 9 patients (75%) with Stage III; and 5 of 5 patients (100%) with Stage IV HD EBV DNA was detected in 9 of 25 cases tested (36%). LMP1 was seen in 39 of 87 cases (45%). EBER and LMP1 positivity were higher in children and older adults than in adults aged between 15-50 years. Immediate early mRNAs (BHLF:Bam H-fragment, lower strand frame) was seen in a single patient., Conclusions: HD in Korea showed a high incidence of mixed cellularity subtype and a high prevalence of EBV. EBV was detected in all subtypes, including a case of nodular lymphocytic predominance, and in all age groups, and showed correlation with mixed cellularity subtype and higher clinical stage. The expression of EBER and LMP were more frequently seen in children and older adults, suggesting a lowered immune surveillance in those age groups or a different pathophysiology of HD among different age groups.

Background: Incidence of condyloma acuminatum is not well known. Descriptive data are usually based on selected groups of patients. This study aims at giving incidence of the clinically defined disease in a well-defined area, thought to be representative for Sweden outside the capital city., Methods: Data from people with condyloma acuminatum seeking medical attention were collected during a two-year period, 1989-90, in a middle-sized urban area in Sweden. A person with symptoms and a clinical picture consistent with condyloma was considered a case., Results: Overall incidence was 2.4 per 1000. The highest age specific incidence occurred in the age group 20-24 years, 12 per 1,000. Women 15-19 years old had an incidence of 14 per 1,000. The total female to male ratio was 1.3., Conclusions: Women more often than men had a mixture of exo- and endophytic condylomata. Condyloma as another and complementary indicator of changing sexual behavior deserves further interest.

Background: The Epstein-Barr virus (EBV) has been linked to several human malignancies, including Hodgkin's disease (HD). In addition, epidemiologic studies have shown differences in HD occurrence in different parts of the world. The authors studied 27 cases of Hodgkin's disease from Mexico to determine the prevalence of EBV in HD in this developing nation., Methods: The Epstein-Barr virus was investigated using in situ hybridization with the EBER1 probe. Immunohistochemical studies were performed on paraffin sections. Cases from both adult and pediatric age groups were included. Correlations with histologic subtype, clinicopathologic features, and immunophenotype were determined., Results: Epstein-Barr virus sequences were identified in 18/27 (67%) cases. Positivity correlated with histologic subtype: 0/1 lymphocyte predominant; 6/13 (46%) nodular sclerosis; 7/7 mixed cellularity (MC) (100%); and 5/6 (83%) lymphocyte depleted (LD). The proportion of cases classified as MC and LD (13 of 27) was greater than that found in the United States and other developed countries. The immunophenotypic profile was appropriate for Hodgkin's disease, with all cases of classic Hodgkin's disease positive for CD30 (Ber-H2) and 18 cases expressing CD15. One case of lymphocyte-predominant Hodgkin's disease was CD20 (L26)-positive as were three cases of classic Hodgkin's disease. Patient age ranged from 5 to 65 years, with a median of 29 years., Conclusions: The EBV is associated highly with HD in Mexico, and this prevalence rate is found in all age groups. A strong correlation between EBV expression and histologic subtype was confirmed, with 92% of MC and LD subtypes found to be positive.

Knowledge of HPV infection is a rapidly changing area which presents a diagnostic and therapeutic dilemma. The clinical expression of HPV infection is highly variable and includes spontaneous regression and recurrence. A variety of molecular biologic methods are available for HPV detection and typing. The role of these diagnostic tools in clinical management is currently being defined. Several therapy options exist, and the choice of treatment depends on the physician and the circumstances and desires of the patient. The management of the patient with HPV includes recognition that the disease process cannot necessarily be cured, nor can the viral infection be totally or reliably eradicated from the genital tract with current methods.

Methods: In an attempt to investigate an association between the finding of clue cells in Papanicolaou-stained (PAP) smears and cervical intraepithelial neoplasia (CIN), a total of 6150 smears from 1976 were re-investigated., Results: Clue cells representing bacterial vaginosis were present in 10% of the PAP-smears. CIN II and III alone, as well as all CIN cases, were more common in women with bacterial vaginosis (p < 0.001). Histologically CIN III/carcinoma in situ was found in nine patients with and in 16 patients without bacterial vaginosis. The relative risk of having CIN III/carcinoma in situ if the women had bacterial vaginosis was 5.0 with 95% confidence interval of 2.2-11.6., Conclusions: The possibility exists that bacterial vaginosis is in some way associated with the development of cervical intraepithelial neoplasia, i.e. as a cofactor to human papilloma virus. Therefore, bacterial vaginosis must be taken in consideration in future studies on CIN.

To elucidate sites of SRV-2/W persistence, tissue DNA from three groups of naturally infected Macaca nemestrina was analyzed for provirus: vertically transmitted, viremic, seronegative macaques; horizontally transmitted, viremic, seronegative macaques, and nonviremic seropositive macaques. In viremic animals infected vertically, provirus was found in many tissues, whereas in those infected horizontally, proviral DNA was limited. In V-Ab+ macaques, provirus was detected in bone marrow and/or ileocecal junction, confirming the presence of provirus in V-Ab+ animals.

Objective: To find the prevalence of HPV infection in women attending a sexually transmitted disease clinic in Hong Kong., Method: Cervical HPV infection was identified by cervical cytology and DNA filter in-situ-hybridization (Virapap) techniques in 207 women attending a social hygiene clinic. Other risk factors for cervical cancer were assessed and any association with HPV infection was sought. Statistical analysis was carried out using the chi 2-test., Result: The prevalence of HPV infection in the 207 Chinese women was 8.2% by cervical smear and 12.6% by DNA filter in-situ-hybridization. Risk factors for cervical cancer were not significantly associated with HPV infection in this group, 95% of whom were prostitutes., Conclusion: The prevalence of HPV infection in this group at high risk for cervical cancer is higher than in low-risk pregnant women, however the prevalence of HPV infection in Hong Kong is at the low end of the range of figures quoted for Caucasians. The cause of such a low prevalence is yet to be determined.

The vaginal microbial flora of 106 women with histopathologically confirmed cervical intraepithelial neoplasia and 79 women without disease, was evaluated for Gardnerella vaginalis, Trichomonas vaginalis, Candida albicans and other yeasts. Flora morphology was assessed by gram staining of secretions. Cervical cultures were examined for Herpes Simplex virus, Cytomegalovirus and Neisseria gonorrhoeae. Chlamydia trachomatis antigens in cervical secretions were detected by enzyme immunoassay. Human Papillomavirus was identified by koilocytosis in cytologic or histopathologic specimens. Human Papillomavirus infection (P less than 0.00001), vaginal infection with Mycoplasma hominis (P = 0.012) and abnormal vaginal flora (P = 0.006) were significantly associated with CIN, suggesting that CIN may be promoted by vaginal microorganisms in conjunction with human papillomavirus cervical infection.