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Infection with human papillomavirus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV infections, whereas several other primary immune defects result in severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them., (Published by Mosby, Inc.)

Background: Human papillomavirus (HPV) infection of the genital mucosa is thought to require trauma to the cervicovaginal epithelium. Therefore, we determined whether a cytology specimen collection procedure (Pap smear), which disrupts the epithelium by design, renders the cervix more susceptible to HPV infection in a primate model., Methods: In a series of female rhesus macaques, a speculum examination was performed with (n = 8) or without (n = 4) a cytology specimen collection procedure as it is commonly practiced in a gynecology clinic. An internal digital examination was performed after specimen collection using Surgilube (n = 4) or 1% iota-carrageenan, a previously indentified HPV inhibitor (n = 4) as the lubricant. The cervix was then inoculated with HPV16 pseudovirions expressing red fluorescent protein. After 3 days, the reproductive tracts were excised and the cervix was cryosectioned. Sections were analyzed by fluorescent confocal microscopy for the number of red fluorescent protein-positive keratinocytes., Results: Substantial infection of the ectocervix, the transformation zone, and the endocervix was detected, but only in conjunction with the cytology specimen collection procedure (cytology using Surgilube vs without cytology using Surgilube, mean = 84 infectious events per section vs mean = 0.05 infectious events per section, difference = 84 infectious events per section, 95% confidence interval = 19 to 384 infectious events per section). When the carrageenan gel was substituted for Surgilube for an internal digital examination, the mean number of infectious events decreased (carrageenan gel vs Surgilube, mean = 3.5 events per section vs mean = 84 infectious events per section difference = 81 events per section, 95% confidence interval = 33 to 213 events per section)., Conclusions: These findings indicate that cytology screening in women might lead to a transient enhancement of susceptibility to HPV infection and that use of a carrageenan-based gel during the examination might mitigate this enhancement.

Human papillomavirus (HPV) is a DNA virus that presents tropism for epithelial cells, causing infections of the skin and mucous membranes. Replication of HPV occurs in the nuclei of squamous cells and its life cycle is directly related to the differentiation program of the host cell. To date, nearly 100 different types of HPV have been characterized and there is a large number of other types that have not been sequenced yet. Besides being responsible for benign lesions of the skin and mucous membranes, HPV is also involved in the development of various mucocutaneous tumors: Bowen's disease, non-melanoma skin cancers and genital carcinomas. This review discusses the characteristics of HPV, malignant and benign mucous and skin manifestations caused by HPV, besides the main methods of detection and typing of the virus.

Background: To determine the age-stratified HPV prevalence rate and the risk factors of life-style associated with HPV infection among women in rural China., Methods: An age-stratified, cross-sectional survey of 941 women between 16-59 years old was conducted in rural China. Carcinogenic HPV infection was determined using Digene's Hybrid Capture II HPV DNA test and interviews of life-style were conducted. Odds ratios (OR) and 95% confidence interval (CI) from the logistic regression models were used to determine the risk factors associated with HPV., Results: Among 941 women, 745 who had sexual intercourse underwent a cervical examination. The prevalence rate of 13 carcinogenic HPV infections among women 20-59 years old was 15.97%. the rate of HPV prevalence in the 25-34 age group was statistically lower than that in 20-24 and 35-59 age groups (X²=13.3, P=0.0013). The OR of bathing every 7-19 days, 20-180 days, less than once every 180 days vs. bathing at least once a week were 1.19, 1.83 and 2.29 respectively and they had a dose-response relationship (Trend Test: P=0.003). The OR of women aged 25-34 age group vs. 20-24 age group was 0.40 (0.16 - 0.97) and the OR of bathing once every 180 days or less vs. at least once weekly was 2.22 (1.14 - 4.33) adjusted for the other confounding factors,., Conclusions: The HPV prevalence rate was lowest among child bearing women aged 25-34 year. Also, personal hygiene is significantly associated with the HPV infection in this area, regardless of age.

Objective: Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV., Methods: Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types., Results: In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09-1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27-2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99-2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34-0.97)., Conclusions: Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

Background: We performed a study to better characterize the natural history of genital human papillomavirus (HPV) infection in a cohort of closely followed adolescent women., Methods: A cohort of 60 adolescent women was followed over a 2.2-year period, on average. A median of 41.5 self-collected vaginal and clinician-obtained cervical swabs were obtained from each subject., Results: HPV was detected in 45.3% of all adequate specimens, by use of a polymerase chain reaction/reverse blot strip assay. Oncogenic--or high-risk (HR)--HPV types were detected in 38.6% of specimens, and nononcogenic--or low-risk (LR)--types were detected in 19.6% of specimens. During the entire study period, 49 of 60 subjects tested positive for HPV (cumulative prevalence, 81.7%). The most frequently detected HR types were HPV types 52, 16, and 59. Infections with multiple HPV types were common. The median duration of persistence of a specific HPV type was 168 days, and HR types were more persistent than LR types. Abnormal cervical cytological results occurred in 37% of the adolescent women and were significantly associated with HR HPV infection., Conclusions: The cumulative prevalence of HPV infection in sexually active adolescent women is extremely high, involves numerous HPV types, and frequently results in cervical dysplasia.

Background and Objectives: Human papillomavirus (HPV) is the primary cause of cervical, anal, and other anogenital cancers, but risk factors for penile HPV detection in men have not been well-characterized., Goal: The goal of this study was to identify correlates of penile HPV detection in ethnically diverse men attending a sexually transmitted disease clinic., Study: A cross-sectional investigation was conducted among 393 men. Participants completed a risk-factor questionnaire and underwent testing for penile HPV DNA. Presence of HPV DNA was assessed using polymerase chain reaction with PGMY primers and reverse line blot genotyping. Logistic regression analyses were conducted to identify variables associated with any-type, oncogenic, and nononcogenic HPV., Results: Circumcision was associated with reduced risk for oncogenic, nononcogenic, and overall HPV. Regular condom use was associated with reduced risk for oncogenic and overall HPV., Conclusion: These findings, if confirmed by other studies, could impact public health practices and messages regarding HPV.

Muslim women are known to have lower incidences of cervical cancer and/or human papillomavirus (HPV) infection. Here we aim to determine any association that may be present between the oncogenic HPV16/18 infections and abnormal cytological lesions along with demographic and other attributes among Indian Muslim women (n = 478) and compare with the neighboring Hindus (n = 534) from a prospective cohort study. Agewise distribution of both subject-groups is similar. HPV16/18 infection is present in 9.6% Muslims and 7.5% Hindu women. Jointly atypical cells of undetermined significance (a typical cells of undetermined significance) and HPV16/18 are present in seven Muslim and two Hindu women. No high squamous intraepithelial lesions or cervical cancer is detected at the baseline. HPV16/18 infections show trends that varied with age, a nonlinear trend among Muslim women. In Hindu women the prevalence is highest at age < or =24 years, which linearly drops with increasing age. Abnormal cytology increases significantly in both religion-groups with increasing age. The data show that these Indian Muslim women are equally susceptible to HPV16/18 infection and for the development of abnormal cytology. There is a paucity in epidemiological data, which justifies the need to screen women of all religions for cervical cancer (that includes oncogenic HPV testing).

Background: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented. GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART., Study Design: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing., Results: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not., Conclusion: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.

Objectives: In women with HIV-associated immunosuppression, HPV infections have an increased risk of progression to high-grade cervical intraepithelial neoplasia (CIN). With the HAART-induced prolonged survival and more protracted clinical course of AIDS, progression of CIN to cervical cancer (CC) has become a clinically relevant issue, and the mechanisms responsible for HIV-HPV interactions need further elucidation. The study design and analysis of the baseline data of our new project are presented., Material and Methods: This project is a combination of a prospective cohort study of HIV- and HIV+ women, and a retrospective analysis of CIN lesions and cervical cancer. Up to the present, 244 women have been enrolled (17 HIV+) and subjected to epidemiological interview, colposcopic examination, sampling for HPV testing and typing (PCR, InnoLiPA), and HPV serology. The retrospective series of biopsies were analysed for 13 biomarkers (monitoring key molecular events) using immunohistochemistry and tested for HPV by PCR and TaqMan., Results: HIV- and HIV+ women differ in their exposure status to many of the key epidemiological risk factors of cervical cancer, the most significant ones being number of sexual partners (p = 0.0001), age at onset of sexual activity (p = 0.002), and contraception (yes-no) (p = 0.009). The differences in the baseline clinical observations are less dramatic; HIV-positive women had more frequent HSIL PAP tests (p = 0.040), CIN2 or higher in cervical biopsy (p = 0.049), and external genital warts (p = 0.019). The factors predicting intermediate endpoint markers of cervical cancer, i.e., HSIL PAP smear, ATZ2 in colposcopy, and high-grade CIN in biopsy were analysed in univariate and multivariate regression models. All factors significant in univariate analysis were entered in the multivariate model; HIV-status and Pap smear history maintained their independent predictive power of the HSIL Pap test. The most powerful predictor of ATZ2 colposcopy was HSIL in Pap test. Only the HSIL Pap test and ATZ2 colposcopy remained significant independent predictors of high-grade CIN (p = 0.0001 and p = 0.008, respectively) in the multivariate model., Conclusions: The three intermediate endpoint markers are closely interrelated, but predicted in part by different covariantes in the causal pathway to cervical cancer. To elucidate whether the increased risk of HIV-positive women to high-grade CIN is due a) to their different exposure status to the risk factors, b) to the direct effects of HIV, or c) to molecular interactions between HIV and HPV, we need to complete these analyses separately in HIV+ and HIV- women.

The association between dietary intake and persistence of type-specific human papillomavirus (HPV) infection, during a 12-month period, among 433 women participating in the Ludwig-McGill HPV Natural History Study was evaluated by use of a nested case-control design. Dietary intake was assessed by a food-frequency questionnaire at the month-4 visit. HPV status was assessed at months 0, 4, 8, and 12 by polymerase chain reaction (MY09/11). Only women who ever tested positive for HPV were included in the present study: 248 had transient HPV infections (1 of 4 positive tests or nonconsecutively positive), and 185 had persistent HPV infections (> or =2 consecutive tests positive for the same HPV type). Risk of type-specific, persistent HPV infection was lower among women reporting intake values of beta-cryptoxanthin and lutein/zeaxanthin in the upper 2 quartiles and intake values of vitamin C in the upper quartile, compared with those reporting intake in the lowest quartile. Consumption of papaya > or =1 time/week was inversely associated with persistent HPV infection.

We present a case of 29-year-old female who underwent an ABO-incompatible living kidney transplantation from her father. The serum creatinine (s-Cr) level of this patient was stabilized about 1.1-1.2 mg/dl during the first 3 months after the transplantation. Thereafter, the function of allograft was deteriorated gradually. A biopsy performed on post-transplant day (PTD) 520 to evaluate a rise in creatinine revealed an interstitial nephritis and chronic renal allograft nephropathy. The renal function worsened persistently, although we increased the dosage of immunosuppressant subsequently. The following biopsy performed on PTD 630 showed a suspicion of BK virus nephropathy, with a mass of tubular epithelial nuclear inclusions and an interstitial nephritis. The diagnosis of BK virus nephropathy was confirmed on the immunohistochemistry staining using anti-SV40 antibody and PCR analysis. Despite reducing the immunosuppressants, the function of the allograft worsened progressively and was lost on PTD 912.

Female sex workers in low priced brothel areas in Denpasar, Bali, Indonesia participated in an intervention study designed to promote condom use and sexually transmitted disease (STD)/AIDS prevention. The intervention provided educational sessions for sex workers, STD treatment for sex workers, condom distribution, and media for clients. The brothel areas were divided into high and low areas for programme effort. The high effort areas received a more intensive behavioural intervention than the low effort areas. A clinic was available for STD treatment in both areas. Behavioural surveys and STD testing were used to evaluate the programmes. About 600 were evaluated for several STDs and completed personal interviews at enrolment and at six-month intervals during the 18-month study. About 50% of women were new to the study at each round. Human papillomavirus (HPV) testing of cervical swabbed specimens, using polymerase chain reaction methodology, was performed at the beginning of the study and 18 months later. Human papillomavirus infection was initially high in these women (38.3%) and declined to 29.7% after 18 months (P <0.01). The prevalence of HPV infection declined with age (P <0.01). HPV infection was associated with a number of STD symptoms that were reported in personal interviews. These associations were stronger in the first time period. Infection with Neisseria gonorrhoeae was associated with HPV infection at baseline (P =0.03). HPV infection declined in the study area with the more intensive educational programme (P <0.01). The prevalence of HPV infection declined over time and was associated with study area and age of woman.

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 and Objective: Human papillomavirus (HPV) is a major cause of invasive cervical cancer. Identification of HPV determinants might allow for targeting of high-risk groups for cervical cancer., Goal: The goal was to estimate the HPV prevalence and its determinants among women from the general population of Barcelona., Study Design: We studied a random sample of female residents in metropolitan Barcelona, Spain (n = 973). Information was obtained through personal interviews and laboratory testing of cervical exfoliated cells. HPV was detected using a GP5+/6+ polymerase chain reaction assay., Results: The average age of participants was 43 years (standard deviation = 16.1 y) and the percentage of lifetime monogamy was 79%. The age-adjusted HPV prevalence was 3.0%. Independent HPV determinants were being born overseas (odds ratio [OR], 8.1; 95% confidence interval [CI], 1.9-33.5), being divorced (OR, 6.7; 95% CI, 1.9-24.3), reporting more than one sexual partner (OR, 2.6; 95% CI, 1.0-6.5), and smoking marijuana and related products (OR, 5.2; 95% CI, 1.2-21.7). Use of condoms with regular partner was protective (OR, 0.14; 95% CI, 0.02-1.0)., Conclusion: The study confirms a low overall HPV prevalence in a largely monogamous population. The protection observed with condom use needs further evaluation.

Background: On a global scale, the New Independent States (NIS) of the former Soviet Union have an intermediate incidence of cervical cancer, the main etiologic factor of which is human papillomavirus (HPV), a major sexually transmitted disease (STD). Recently, the prevalence of all STDs has exploded in these countries., Goal: The goal of this study was to examine the sexual habits and HPV prevalence among females in three NIS countries., Study Design: In this multinational (European Community-funded) trial, a series of 3,175 consecutive female patients were examined for HPV status (by Hybrid Capture II) at six clinics in Russia, Belarus, and Latvia. A meticulous survey of their sexual habits and other potential risk factors of HPV infections was made by structured questionnaire., Results: Three categories of patients were examined: those attending STD clinics (n=722), gynecological patients (n=761), and those who participated in cervical cancer screening (n=1,692). These three categories were significantly differentiated by a large number of key variables, including the HPV detection rate (44.9% of STD patients, 39.8% of gynecological patients, and 24.5% of those who were screened). A wide variety sexual habits of these subjects were predictors of the HPV status in univariate analysis. Binary logistic regression analysis found that six different variables remained as independent predictors of HPV status. Patient category (STD) and (young) age were two highly significant predictors of increased risk (P<0.0001), whereas having a nonsmoking partner and having zero or one partner during the past 2 years were significant protective factors (P=0.004 and P=0.007, respectively)., Conclusion: The results of this study indicate that women and girls in these NIS countries are conservative in many key characteristics of "high-risk" sexual behavior, such as age at onset of sexual activity, number of partners, and casual sex partners. HPV-positive and HPV-negative groups are clearly distinguished by the same variables identified as the key risk factors of HPV infection and cervical intraepithelial neoplasia in Western countries.

Cervical cancer remains a leading cause of death for women in the developing world, and the treatment of preneoplastic cervical lesions is a considerable public-health burden in the developed world. There is unambiguous evidence that human papillomaviruses (HPVs) trigger the development of cervical and other anogenital malignancies, and that continued expression of HPV antigens in the tumours drives the neoplastic progression. The viral cause of cervical cancer is also its Achilles heel. Prophylactic vaccines to prevent HPV infection and therapeutic vaccines targeted at the HPV tumour antigens are in clinical trials. A firm grasp of the molecular pathogenesis of HPVs and the natural history of genital HPV infections, combined with greater understanding of how to trigger effective immune responses, offers hope for the elimination of HPV-associated diseases.

High risk human papillomaviruses (HPVs) have emerged as risk factors for anal carcinoma, of which incidence is higher in HIV-positive patients than in the general population. The aim of our study was to investigate the prevalence and risk factors for anal HPV infections in HIV-positive patients with or without history of anal intercourse. Fifty HIV 1-infected patients (36 men and 14 women) were tested at entry and followed-up every 3 months for one year for the presence of anal HPV DNA by the Hybrid Capture II trade mark assay. A series of 50 HIV-negative subjects matched for age and sex served as controls. At enrollment, anal HPV DNA was present in 29/50 HIV-positive patients (58 %) and in 3/50 control subjects (6 %). High risk (HR) HPV genotypes were detected in 20/50 HIV-positive patients (40 %) with no difference in homosexual men and other HIV-positive patients. Risk factors for HPV infection were CD4 + cell counts less than 500/microL (RR: 2.13 [95 % CI: 1.0-4.7]) and history of anogenital warts (RR: 2.36 [95 % CI: 1.2-4.6]). The HPV load was higher in patients with CD4+ < or = 500/microL than in patients with CD4 + > 500/microL (p < 0.04). During the follow-up, anal HR HPV DNA was repeatedly identified at high levels in 5 HIV-positive patients. There is some convincing evidence that HIV-positive patients with low CD4+ cells, whatever the routes of HIV transmission, have a high rate of anal HPV infection and might be at increased risk of developing anal neoplastic lesions. Identifying HR HPV infection might be warranted in immunosuppressed patients.

Little is known about the prevalence and persistence of human papillomavirus (HPV) in older women, or about the association between hormone replacement therapy (HRT) use and HPV detection. Like oral contraceptives, HRT hormones may upregulate viral expression and subsequent risk of genital cancer. Postmenopausal women seeking routine gynecologic care were evaluated for HPV infection, testing cervical/vaginal cytology by PCR/DNA sequencing. The prevalence of HPV was 14%; 6% had oncogenic types and 5.8% had persistent infection. Although risk of HPV detection was non-significantly elevated after adjustment for age and HPV-related risk factors among current (adjusted odds ratio (OR)=2.3) and past (adjusted OR=3.2) hormone users compared to never users, past users had a significantly higher risk using combination HRT regimens with increasing duration (adjusted OR=1.8 per year; 95% confidence interval (CI)=1.1-3.1). These findings suggest that a significant percentage of older women are infected with HPV. This may put them at increased risk of genital cancers with longer use of HRTs. Additional studies are needed.

Changes to the present age policy of cervical screening are currently under consideration. We conducted a retrospective matched case-control study and cost analysis study to identify risk factors for the development of an abnormal smear after age 50 and to determine the impact of age-restricted cervical screening on the annual cost of the screening program. All women (229) from an 11-year birth cohort who developed an abnormal smear at age 50 or over were age-matched for two controls with negative smears. Routine screening smears taken between age 48 and 52 were tested for human papillomavirus (HPV) subtypes 16 and 18. Epidemiologic data were collected by postal questionnaire. Changes in costs under a policy of HPV testing and age-restricted screening were assessed. We found that HPV 16 status was the only independently significant risk factor for abnormal cytology after age 50 with an odds ratio of 10.26 (95% CI 1.25-84.11). A policy of early withdrawal from screening at age 50 on the basis of HPV testing would produce net cost savings. These findings suggest that HPV testing could be a valuable means of identifying the small proportion of women still at risk after 50, and of releasing health care resources.

A high incidence of initial infection with human papillomavirus (HPV) was previously reported in a cohort of 608 women monitored at 6-month intervals for 3 years. Risk factors for subsequent infections with different HPV types and whether antibodies against HPV-16 virus-like particles (VLPs) protected against these infections were examined. Subsequent infections with HPV are very common. Seventy percent of women acquired a different HPV type within 24 months of the initial infection. Risk factors included being nonwhite, having an increased number of male sex partners, and having had a new male sex partner. Use of oral contraceptive pills was protective. A sustained high level of IgG antibody to HPV-16 VLPs was associated with reduced risk for subsequent infection with HPV-16 and its genetically related types (i.e., HPV-31, -33, -35, -52, and -58).

Oral contraceptives (OC) are a risk factor for female genital cancers and in vivo studies have shown that progestins stimulate human papillomavirus (HPV) gene expression. A similar role for hormone replacement therapy (HRT) has received little evaluation. Cervical/vaginal specimens were obtained to detect HPV from postmenopausal women (n = 429) seeking annual gynaecologic care. HPV was detected in 14% of women and 4.4% had high-risk, oncogenic types. HPV prevalence was similar across current, past and never HRT users. After adjustment for HPV-related risk factors, current and past user status showed no increased viral detection compared with never users. HRT duration also did not elevate risk among current users. However, longer duration (adj. OR 1.5/year, 95% CI 1.0-2.3) and longer latency (adj. OR 1.2/year, 95% CI 0.9-1.7) among past users of oestrogen/progestin regimens were associated with greater risk. Overall use of HRTs was not associated with HPV detection or disease. However, past users of combination HRTs had significantly greater risk of HPV detection with longer HRT duration and latency, similar to OC-HPV findings. The recommendation that postmenopausal women continue HRTs long term may lead to an increased development of HPV-related diseases, of particular concern among those who discontinue HRTs and subsequent gynaecologic care for early cancer detection.

Background: Over the past few years a series of research projects has shown that the scant or deficient immune response in HIV infection may be secondary to reduced cell resistance and/or the uncontrolled formation of free radicals. In line with these findings, subjects with HIV infection present a deficit of polyunsaturated fatty acids (the principal components of cell membranes) and many antioxidating substances, like Vitamin E and glutathione peroxidase. The high incidence of heterosexual transmission of HIV has now shown the close correlation between HIV infection and HPV infection. By analogy, we wanted to ascertain whether these deficits were also present in subjects with HPV infection and dysplastic and neoplastic lesions of the uterine cervix. Published data confirm that a HPV-positive subject has an increased risk, ranging from 40 to 200%, of contracting HIV infection., Methods: Eighty women with HPV infection of the genital tract, at various stages. Blood levels of vitamin E and polyunsaturated fatty acids were measured using gas-chromatography; glutathione was assayed using the spectrophotometric technique., Results: The alternation of the aforesaid parameters is correlated to the progress of infection and increases with the severity of lesions; Statistically significant data were recorded by comparing the group with condylomatosis with patients diagnosed with cervical carcinoma (p<0.001)., Conclusions: The increased possibility that some patients are affected by an association of HPV and HIV depends on the anomalous or scarce function of many immunocompetent cells, as well the quantitative immune deficiency induced by the initial virus and the presence of various mechanisms that facilitate the development of the infection.

Few studies have evaluated the role of passive smoke exposure and cervical neoplasia risk. We assessed the role of active and passive cigarette smoke exposure and risk of cervical squamous intraepithelial lesion (SIL) in a case-control study based in a South Carolina Health Department; 59 high-grade SIL (HSIL) cases, 313 low-grade SIL (LSIL) cases and 427 controls were recruited and interviewed. Passive cigarette smoke exposure was significantly (P < 0.05) associated with high grade SIL (adjusted odds ratio (aOR) = 2.2) and low-grade SIL (aOR = 1.4). Active smoking was associated with SIL only among White women (aOR = 1.8). High-risk human papillomaviruses (HR-HPVs) appear to interact with active cigarette smoking to increase HSIL risk. HSIL cases compared with LSIL cases were significantly more likely to be HR-HPV positive current smokers (aOR = 3.0; 95% CI: (1.2, 7.7)). These data suggest that active and perhaps passive smoke exposure may be important co-factors in HSIL development among HR-HPV positive women.

Objectives: The aim of this work was the assessment of correlation between different types of HPV and chosen factors: the number of pregnancies, childbirths and smoking habits., Materials and Methods: Patients were examined in the Gynaecology Clinic, Silesian Medical Academy in Zabrze from 1998 until 2000. They were either hospital patients or women subjected to routine cytological examination. The smears were simultaneously collected for both cytooncologic examination and PCR identification of HPV viruses. Cytological smears were classified according to the Bethesda system., Results: A relationship between the presence of HPV and number of pregnancies or childbirths was confirmed as well as the relationship between smoking and the presence of HPV genome. The higher number of pregnancies or childbirths the higher frequency of HPV presence is. HPV presence was more frequent in the group of smoking women., Conclusions: A relationship between the presence of HPV and the number of past childbirth or pregnancies was found. The statistically significant correlation between smoking and the risk of HPV infection was also confirmed.

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.)

Background: A multicentre epidemiological survey was carried out in order to determine the prevalence of, and risk factors for, persistent cervical human papillomavirus (HPV) infection in women in Hungary., Methods and Results: A total of 728 women were examined for the prevalence of HPV. The estimated overall rate of HPV infection was 17%. In univariate analysis the strongest predictors were young age (< or =24 years), unmarried family status, smoking, a pathological Papanicolaou (Pap) smear, having a condyloma and previous gynaecological cancer in the family (age and marital status being the most important predictors). In multiple regression analysis, young age (< or =24 years)(odds ratio = 1.86, 95% confidence interval = 1.19-2.90, P < 0.01), smoking (1.78, 1.17-2.71, P < 0.05), an abnormal Pap smear (6.92, 2.68-17.84, P < 0.001), having a condyloma (4.22, 1.42-12.58, P < 0.01) and living in a region where the unemployment rate is relatively high (1.56, 1.24-2.82, P < 0.01) were associated risk factors for HPV infection., Conclusions: The prevalence of HPV infection in young women in Hungary is high. Screening for HPV is suggested only in women with an unfavourable gynaecological history who are < or =24 years old.

We assessed the influence of hormonal (oral, injectable, or levonorgestrel [Norplant, Wyeth-Ayerst, Philadelphia, PA]) and barrier methods of contraception on the risk of cervical squamous intraepithelial lesions (SIL), while adjusting for high-risk (HR) HPV infection. Subjects were women receiving family planning services through the state health department clinics from 1995 to 1998. We selected 60 cases with high-grade cervical/SIL (HSIL) and 316 with low-grade cervical/SIL (LSIL) and controls (427 women with normal cervical cytology) and analyzed cervical DNA for HR-HPV, using Hybrid Capture I (Digene; Gaithersburg, MD). When assessing ever use, duration, recency, latency, and age at first use, neither oral contraceptives (OC), Norplant, nor injectable use was associated with an increased risk of SIL development after adjusting for age, age at first sexual intercourse, and HR-HPV positivity. Among HR-HPV-positive women, longer duration barrier method use was associated with a reduced risk of SIL. This finding has important clinical implications for SIL prevention among HR-HPV-infected women.

Human papillomavirus, herpes simplex virus, and both hepatitis A and B are some of the most common sexually transmitted infections (STI) worldwide. They are preventable, but unlike bacterial STIs the person may harbor the virus in her or his body for life with periodic recurrences of active infection. Viral STIs have long-term health consequences, some of which are serious and life threatening. Nurses not only care for individuals who have a viral STI but also can provide education for prevention.

Background: Secondary malignant diseases are late complications after allogeneic bone marrow transplantation (BMT). Anogenital lesions associated with human papillomavirus (HPV) infection have been described in renal transplant recipients but not after BMT. HPV types 16 and 18 are strongly linked to the malignant transformation., Methods: In a series of 238 patients with allogeneic BMT, three had anogenital lesions. We looked for HPV in DNA extracted from embedded tissue to study HPV genotypes, p53 expression, and ploidy., Results: In two patients, HPV sequences were detected. One of them, with giant condyloma, had HPV type 18 and two aneuploid clones, but p53 expression was not found., Conclusion: As in solid organ transplant recipients, anogenital condyloma may develop after BMT. Because the oncoprotein of HPV is able to bind and to degrade p53, it may lead to genetic instability, and subsequently to malignant transformation.

Background: Human papillomaviruses (HPV) are common human pathogens and are classified into more than 80 different types. These viruses produce benign warts in many cases and aggressive squamous cell carcinomas in other cases., Objective: The goal of this review is to update the reader on the epidemiology, pathogenesis, and therapy of HPV infections. Nonanogenital warts are transmitted by skin-to-skin contact while anogenital warts are usually transmitted sexually. Both types of warts produce much morbidity but rarely undergo malignant transformation. They are commonly treated with surgical or cytodestructive therapy, but immunomodulatory agents, such as imiquimod, have been proven to be very effective in anogenital warts and are being evaluated in nonanogenital warts. Other types of HPV have marked oncogenic potential such that over 99% of all cervical cancers and over 50% of other anogenital cancers are due to infection with oncogenic HPV. Many cofactors, such as cigarette smoking, genetics, and helper viruses, have potential roles in HPV oncogenesis, but their relative contributions are poorly understood. Other control measures for warts and HPV-associated cancers are under study, but the greatest future potential may be from the development of prophylactic and therapeutic vaccines., Conclusions: Infection with HPV is very prevalent as are the clinical manifestations of this family of pathogens. Improved therapies for warts (e.g., imiquimod) have recently become available. Vaccines for HPV offer hope for future interventions for warts as well as for prevention of anogenital malignancies.

Objective: To compare the prevalence of genital human papillomavirus (HPV) infections in sexually abused and nonabused preadolescent girls and assess the feasibility of conducting a longitudinal study of the natural history of HPV infection in this population., Method: Consecutively referred, 5- to 12-year-old girls who were evaluated for sexual abuse by a Child Advocacy and Protection Team were invited to participate in the study. During a standard forensic medical examination, 2 specimens for HPV testing were obtained (one by rubbing a Dacron swab over the perineum and the other by lavaging the vagina with phosphate-buffered saline). The specimens were evaluated for HPV DNA by polymerase chain reaction using MY09/11 consensus primers and high-risk (16,18,31,33,35,39,45,51,52, 56,58) and low-risk (6,11,42,43,44) types were detected with a solution hybridization assay, the SHARP Signal System (Digene Diagnostics). The genital area was examined for warts and subclinical, colposcopic evidence of HPV. Participants were invited to return for longitudinal evaluation at 4-month intervals for 2 years., Results: Sexual abuse was confirmed in 29 (72.5%) of the 40 study participants, suspected in 2 (5%), and ruled out in 9 (22.5%). None of the girls had genital warts or abnormal colposcopic findings. HPV DNA was detected in 5 (16%) of the 31 girls with confirmed or suspected sexual abuse (1 with high-risk and 4 with low-risk types) and none of the nonabused girls (Fisher's exact test). Girls who tested positive and negative for HPV did not differ significantly in age or type of abuse. Despite close telephone follow-up and numerous attempts to schedule appointments, none of the participants returned for follow-up., Conclusions: Genital HPV infection is more common among sexually abused than nonsexually abused girls, with the majority of infections not clinically apparent. Because it is so difficult to study the natural history of these infections in abused children, it may be necessary to draw inferences about the long-term sequelae of pediatric HPV infections from longitudinal studies of girls who voluntarily initiate sexual activity soon after menarche.

Objective: To assess the relationship between circumcision and urethral human papillomavirus (HPV) lesions, and the influence of urethritis on the development of urethral HPV infections on inducing squamous metaplasia of the urethral epithelium., Patients and Methods: The study included 210 heterosexual, HIV-negative men (median age 29 years) who all had female partners with genital HPV infection. The patients were divided into three groups according to clinical findings, i.e. 97 patients with no clinical HPV lesions on peniscopy and urethroscopy, 70 patients with balanopreputial lesions but no urethral lesions, and 43 patients with urethral HPV lesions, including 17 who had associated penile lesions. They all underwent meatopeniscopy for HPV screening, urethral biopsy for histological analysis, and bacterial cultures were taken. The results in each subgroup were compared between circumcised and uncircumcised men., Results: There was no significant difference in the incidence of HPV infection (58% vs 42%, odds ratio, OR, 1.8; 95% confidence interval, CI, 0.98-3.62) between uncircumcised and circumcised men, but this relationship differed with the developmental site of HPV lesions (shaft-foreskin, P<0.02; urethra, not significant). There was also a significant difference in the prevalence of urethritis between uncircumcised and circumcised men (34.5% vs 19%, OR 2.35, 95% CI 1. 08-5.11), and between HPV-infected and uninfected men (41.5% vs 18%, OR 3.17, 95% CI 1.71-5.83). This positive relationship of the prevalence of urethritis for both factors (circumcision and HPV) depended on the type of organism (sexually transmitted disease, not significant; common organism, P<0.02). The frequency of urethritis was related to the site of HPV lesions; urethritis was present in 36% of the patients with preputial HPV lesions, compared with 51% of those with urethral HPV lesions. Chlamydia trachomatis was detected in 1% of the patients without and in 7% of those with HPV lesions. In 68% of the patients, histological analysis of the urethral mucosa showed a squamous metaplasia of the urethral epithelium associated with urethritis., Conclusions: Being uncircumcised did not seem to increase the risk of HPV urethral infection in young men. Genital bacterial infections and urethral HPV lesions appear to be linked. Urethritis can induce squamous metaplasia of the urethral epithelium, which appears to favour the colonization of the anterior urethra by HPVs.

A cytological examination of 425 sexually active females aged 13-17 established cervical HPV infection incidence at 30.3 +/- 2.2% while that of cervical dysplasia--4.5 +/- 1.0%. The risk factors for HPV infection included low education and income level (p < 0.05), number of sexual partners exceeding three (p < 0.05), poor hygienic standards of woman (p < 0.05) and those of partner (p < 0.001) and smoking of more than 5 cigarettes per day (p < 0.001). The risk factors of cervical epithelial dysplasia were number of partners of 5 or more (p < 0.001), poor hygienic standards of male partner (p < 0.001) and smoking of 10 cigarettes and more per day (p < 0.001), etc.

Infectious cervicitis is a common disease in women of reproductive age. A prospective study was carried out including 70 women with clinical manifestations of cervicitis during gynecological and colposcopic examination. In 19 women (27%), Chlamydia trachomatis was demonstrated by direct immunofluorescence in cervical smears. Neisseria gonorrhoeae was isolated in 2 women and 1 had a concomitant infection with Neisseria gonorrhoeae and Chlamydia trachomatis. Mycoplasma hominis and Ureaplasma urealyticum were isolated in 7 patients and 4 had cytological smears consistent with Human Papilloma Virus infection. In the rest 47 patients no etiological agent was found. The results of the present study indicate that the most common etiological cause for infectious cervicitis can be Chlamydia trachomatis and an examination for this organism should me mandatory in women with infectious cervicitis for guiding the correct diagnosis and treatment.

JC virus (JCV) load was determined by using quantitative polymerase chain reaction in cerebrospinal fluid (CSF) of 12 patients with AIDS-associated progressive multifocal leukoencephalopathy (PML) and compared with clinical outcome. JCV loads varied widely (3-7 log10 JCV equivalents/mL of CSF) and were apparently not related to absolute CD4 cell counts or CSF and plasma human immunodeficiency virus type 1 loads. A significant correlation was observed between JCV load and survival time (Spearman's rank correlation, -0.83; P<. 01). Moreover, CSF JCV load decreased and then became undetectable in 1 PML patient receiving cidofovir treatment, and this was associated with clinical improvement. These results show that CSF JCV load may be useful as a prognostic parameter and in monitoring the effectiveness of anti-JCV therapies in PML patients.

Simian virus 40 (SV40) has been introduced into the human population with contaminated polio vaccines between 1955 and 1963. Previous research conducted by southern blot hybridization and recent analysis by PCR have shown the presence of SW0 sequences in human brain tumors, mesotheliomas and osteosarcomas as well as in normal tissues such as blood and sperm fluids. SV40 RNA and T antigen were detected in the same tissues. All the samples were coinfected by BK Virus (BKV), suggesting that BKV may have a helper function for SV40 replication in human cells. The presence of SV40 in human tumors suggests that the virus may be a cofactor in the etiopathogenesis of human neoplasia. In addition, blood and semen may represent the vectors for transmission of SV40 by horizontal infection in the human population.

The role of human papillomaviruses (HPV) in laryngeal squamous cell carcinoma has not yet been established. Thirty-three cases of laryngeal squamous cell carcinoma were analysed for the presence of HPV DNA and compared with 25 cases of normal larynx and 29 cases of laryngeal squamous papilloma in their positivity index. The presence of HPV DNA was analysed by using L1 consensus primers and also by primers specific for the E7 gene of HPV types 16 and 18. Four normal laryngeal samples (16%) were positive for HPV DNA against the 24 samples (82%) (p < 0.001) found for laryngeal papilloma and 16 (48.5%) (p < 0.05) found for laryngeal squamous cell carcinoma. HPV 16 was the type most frequently found in laryngeal carcinoma samples. Our results support an etiologic role for this type of HPV in the pathogenesis of laryngeal carcinoma.

Objective: To identify risk factors for the detection of prevalent and incident anal human papillomavirus (HPV) infection, and HPV persistence among HIV-seropositive and seronegative homosexual men., Design: Longitudinal study of 287 HIV-seronegative and 322 HIV-seropositive men attending a community-based clinic., Methods: Subjects underwent an interview and examination; specimens were collected for HIV serology and assessment of anal HPV and HIV DNA., Results: Anal HPV DNA was detected at study entry in 91.6% of HIV-infected men, and 65.9% of men not infected with HIV. HPV detection was associated with lifetime number of sexual partners and recent receptive anal intercourse (HIV-seronegative men), decreased CD4+ lymphocyte count (HIV-seropositive men), and anal warts (all men). Among men negative for HPV at study entry, subsequent detection of HPV was associated with HIV, unprotected receptive anal intercourse, and any sexual contact since the last visit. Among men positive for HPV at study entry, subsequent detection of additional HPV types was more common among HIV-seropositive men. Becoming HPV negative during follow-up was less common among men with HIV or high HPV levels at study entry. Among those with HIV, HPV persistence was associated with presence of anal HIV DNA, but not with CD4+ lymphocyte count., Conclusions: Risk of anal HPV infection appears to increase with sexual exposure, epithelial trauma, HIV infection and immune deficiency. Incident infection may result from recent sexual exposure or reactivation of latent infection. Further studies are needed to elucidate the mechanism by which HIV DNA in the anal canal increases the risk of HPV persistence.

Background and Objectives: Human papillomavirus (HPV) is strongly implicated in the etiology of cervical neoplasia; however, the frequency, rate, and predictors of neoplastic progression are unknown., Goal: To measure the type-specific prevalence of cervical HPV and the rate of development of cytological abnormalities among a cohort of college women and to elucidate factors associated with acquisition of HPV DNA and progression to cytological abnormalities., Study Design: Women 18 to 40 years of age seeking routine gynecologic care at a university health center were enrolled in a cross-sectional study with prospective, longitudinal follow-up of a subset of women. Demographic and behavioral data were collected using a written questionnaire. HPV DNA was detected in cervical scrapes by polymerase chain reaction using L1 consensus primers and a generic and 25 type-specific probes, and cervical cytological abnormalities were identified by Papanicolaou's (Pap) smear., Results: HPV DNA was detected in 35% of the 414 women in the cross-sectional study; 66% of infections were with intermediate or high cancer risk HPV types. Multiple lifetime sex partners was an independent predictor of prevalent infection. Longitudinal analysis of 205 women showed that detection was transient (HPV DNA absent at follow-up) in 38% of the 84 women who were HPV-positive at enrollment. Persistent detection of the same HPV type at > or = 2 visits occurred in 14% of women and was significantly more common when intermediate or high cancer risk types were present. After 16 months of observation, 9% of HPV-infected women developed low-grade squamous intraepithelial lesions (SIL) and 5% developed high-grade SIL; the risk of incident SIL was 7.8-fold higher among women who had persistent HPV detection with the same type., Conclusions: It was concluded that cervical HPV infection is highly prevalent among college women. Although most infections are caused by intermediate of high cancer risk types, few women (5%) developed high-grade SIL during 16 months of observation.

The objective of this study was to compare the use of molecular hybridization by hybrid capture methodology for human papillomavirus (HPV) with the use of demographic and lifestyle variables as intermediate triage in patients with cytological mild dyskaryosis. The study was designed as a prospective study using regression tree analysis of demographic data in consecutive patients who were subjected to colposcopic evaluation at the colposcopy clinic at the First Department of Obstetrics and Gynaecology, University of Milan (Milan, Italy). A total of 177 women were subjected to colposcopy because of a single routine Pap smear showing mild dyskaryosis. A structured interview, sampling for HPV testing for the detection of viral DNA by hybrid capture methodology, and colposcopic evaluation with cervical biopsies were performed for each subject. The accuracies of molecular hybridization for HPV and of the classification model based on the demographic and lifestyle variables in predicting patients with histologically high-grade cervical intraepithelial lesions were measured. The classification model based on the demographic and lifestyle variables showed comparable results with molecular hybridization for HPV (specificity, 0.75 versus 0.73; sensitivity, 0.61 versus 0.67, respectively). The use of demographic and lifestyle variables appears to be a simple and economic possibility for triaging patients with mild dyskaryotic smears in a screening program.

Human papillomaviruses (HPVs), a large family of small DNA tumour viruses, are unequivocally linked to the induction of benign warts and anogenital cancer. Mechanisms utilized by HPV oncoproteins identify p53 and pRB as important cellular controls. New techniques reveal that novel members of the HPV family may contribute to non-melanoma skin cancer development.

This study provides the first systematic evaluation of papillomavirus type and viral mutation occurring during the course of juvenile-onset recurrent respiratory papillomatosis. One hundred ninety-nine consecutive papillomas excised from 47 children between 1981 and 1996 at The New Children's Hospital in Sydney, Australia, were tested for human papillomavirus (HPV) DNA by PCR. PCR products from the viral upstream regulatory region (URR) enhancer were sequenced, and variation was related to clinical variables. Forty-four of the 47 children had HPV-induced papillomas, with type 11 accounting for 24 (55%) and type 6 accounting for 19 (43%); one (2%) was positive for either type 6 or 11. Overall, 183 (98%) of the 186 samples with amplifiable DNA were HPV positive. There was no change in HPV type over time and no statistically significant association between HPV type and disease aggressiveness. One novel, large-scale URR duplication was identified in an HPV type 11 isolate in the last of a series of six papillomas examined and the first from the bronchus. However, the duplication was not found in HPV type 11 isolates from the associated pulmonary carcinoma and its metastases in other organs. Three of 14 URR point mutations coincided with transcription factor binding sites, but there were no obvious associations with clinical course. Chi-square and multiple linear regression analyses of clinicopathological variables revealed early age at diagnosis (less than 4 years) as an independent predictor of aggressive disease (P < 0.001). A bimodal distribution of the age at diagnosis was noted, with peaks at 2 and 11 years of age.