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The concordance of human papillomavirus (HPV) groups and types was evaluated in 45 sexual couples with both partners HPV infected, by analyzing cervical samples from women and three genital sites (penile brushing, urethral brushing, and semen) from men. When grouping HPV types, no significant HPV group sharing was found between partners, either considering samples from any male site (concordance: 55.5%; P = 0.11) or from each site (concordance by penile brushing, 37.8%; urethral brushing, 24.5%; semen, 22.3%; P > 0.05). Examining individual HPV types, using samples from any male site, concordance was found in 29 (64.4%; P = 0.036) couples; significant concordance was evident for 16 HPV genotypes, the most frequent being HPV-6, -66, -31, -51, and -53. Using samples from specific male sites, concordance was found by penile brushing in 24 (53.3%) couples, urethral brushing in 16 (35.5%), and semen in 7 (15.5%; P = 0.014). Among the 16 HPV types shared by examining samples from any male site, 9 (56.3%) were in common by penile brushing, 11 (68.7%) by urethral brushing, and 6 (37.5%; P = 0.48) by semen. Combined penile brushing and urethral brushing sampling identified all the 29 couples concordant by the three male sites; combined penile brushing and semen detected 26 (89.6%) concordant couples. The most adequate approach to the assessment of HPV concordance in sexual couples could be based on the analysis of individual HPV types and the sampling of men by penile brushing combined with urethral brushing. The high and significant degree of HPV type-specific concordance confirms HPV transmission between sexual partners., ((c) 2007 Wiley-Liss, Inc.)

To study HPV prevalence and HPV types 6, 11, 16, 18, 31, and 33 distribution in cervical smears in a cohort of Greek women. One thousand six hundred thirty-six samples were cytologically evaluated and molecularly analyzed, by PCR based assay. Abnormal cytology was identified in 997 women and 75.4% of them were HPV DNA positive, while 639 had normal cytology and 24.6% were HPV DNA positive. HPV was detected in 62.9% of 256 ASCUS smears, 89.3% of 516 LSIL, 86.7% of 60 HSIL and 47.3% of 165 with cervical carcinoma. Overall, HPV 11 was the most common type (13.4%), followed by 18 (10.3%), 6 (7.2%), 16 (6.4%), 31 (3.4%) and 33 (3.4%). Multiple infections with two (11.3%) or more types, primarily 11 and 18 (4.8%), were also identified. Low-risk types 11 and 6 were common in ASCUS (36.6% and 26.4%, respectively), and high-risk types 16 and 18 in HSIL (42.3% and 30.8%, respectively) and in cancer (51.3% and 41%, respectively). Multiple infections were detected in 2.2% of normal and 31.7% of HSIL. HPV prevalence was 75.4% in abnormal and 24.6% in normal cervical smears. HPV 16 and 18 were the most common types in cancer. Single infection with type 11 and multiple infections with 11 and 18 were more frequent., ((c) 2007 Wiley-Liss, Inc.)

Human papillomavirus (HPV) genotyping could be clinically useful, depending on the results of large, prospective studies like the HPV persistence and progression (PaP) cohort. The cohort is based on genotyping and follow-up of Hybrid Capture-positive women at Kaiser Permanente, Northern California. HPV DNA testing by Hybrid Capture 2 requires denaturation with alkali, possibly damaging the DNA for optimal PCR-based genotyping. A feasibility study was conducted on paired aliquots of anonymized specimens from 100 women with low-grade intraepithelial lesion cytology. Test aliquots were left in denaturant for 10 or 18h at 4 degrees C and then neutralized; comparison aliquots were not denatured but diluted to match the timing, temperature, concentration and salt conditions of the treated specimens. The masked aliquots were tested using a commercialized PCR-based assay that detects of 37 HPV genotypes. There was no overall effect of treatment on test positivity or number of types. HPV16 was marginally more likely to be detected in untreated versus treated aliquots (P=0.09) but HPV45 was marginally more likely to be detected in treated than untreated aliquots (P=0.07), suggesting that these differences represented chance (intra-test variability). It can be concluded that residual Hybrid Capture-positive specimens can be genotyped by PCR after Hybrid Capture 2 processing.

Objective: To perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes., Methods: The cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry., Results: Totally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis., Conclusion: The proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.

Human papillomavirus (HPV) infection is very common but with limited therapies available. Although the prophylactic vaccination will be promoted worldwide soon, it can only show its benefits decades later. For individuals who already have established infections and dysplasias, it has little efficacy. In contrast, the therapeutic vaccines bridge the temporal deficit by fighting against the established HPV infections and HPV-related diseases. HPV oncogenes may be delivered in viral and bacterial vectors, in peptides or protein, in nucleic acid form, or in cell-based vaccines. This review summarizes the clinical trials of HPV therapeutic vaccines under the way and the different preclinical research strategies that are under investigations.

Objective: To evaluate the clinical application value of flexible multi-analyte profiling (xMAP) technology in detecting high-risk human papillomavirus (HR-HPV)., Methods: Totally 1 061 women, aged 21-65 years, were randomly enrolled into the study. Cervical exfoliated cells were used in xMAP technology and hybrid capture II (hc2). Pathological diagnosis was used as golden standard. Consistency of these two methods was assessed., Results: The sensitivity and specificity of xMAP technology were 80.31% and 85.83%, respectively. The positive and negative predictive values were 44.5% and 96.9%, respectively. The Kappa value for consistency between xMAP technology and hc2 was 0.58., Conclusions: The specificity of xMAP technology is similar to hc2 test, but the sensitivity is inferior to hc2. However, these two methods show good consistency in the detection of HR-HPV.

Oncogenic human papillomaviruses (HPVs) are obligate mucosal pathogens and typically cause localized infections. The mucosal surface of the genital tract also provides the first line of defense against genital HPV infection. Although local antibody production following HPV-infection has been demonstrated, their role in protection from cervical disease is unclear. This study evaluated oral and cervical HPV infection and the associated linkage between HPV-16 oral, cervical and serum antibody responses in 103 women with varying grades of cervical intraepithelial neoplasia (CIN). We found that HPV-16 was the most prevalent cervical HPV infection (30/103, 29.1%) but was only detected in 1.1% (1/91) of the oral samples. Both the frequency and magnitude of HPV-16-specific cervical IgA was significantly elevated in women with CIN 2/3 compared with women with CIN 1 (P = 0.0073 frequency; P = 0.0045 magnitude). Women with cervical HPV-16 infection had significantly higher magnitude and frequency of cervical HPV-16 IgA responses than women without cervical HPV-16 DNA (P = 0.0002 frequency; P = 0.0052 magnitude). Despite our contention that mucosal HPV-16 antibody responses within distinct mucosal compartments may be linked, the concordance analysis carried out within and between mucosal compartments and serum suggests that no such linkage exists and that these compartments may be functioning independently of one another. An HPV-16 specific antibody response in one mucosal compartment in women with CIN is therefore not predictive of a response at another.

Objective: Human papilloma virus (HPV) can cause cervical cancer. Risk factors for HPV infection are primarily related to sexual behavior. We determined the prevalence of HPV infection and abnormal cervical cytology in institutionalized women with no previous sexual experience., Methods: The study subjects were 251 patients who sought screening for cervical cancer (45.9+/-9.4 years, mean+/-S.D., range, 14 to 66). They were institutionalized for psychosomatic disorders since childhood, and had no previous sexual experience. In addition to screening for cervical cancer, specimens for HPV testing were collected., Results: No women who were positive for HPV DNA was detected, though 251 women without sexual experiences were screened by the hybrid capture 2 test including 26 types of HPV-DNA., Conclusion: Transmission through means other than sexual intercourse may not exist because we could not detect HPV DNA in 251 women with no previous sexual experience.

Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The six-month cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p = 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIV-negative (60% vs. 51%, p = 0.70) and HIV-positive (55% vs. 63%, p = 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR = 8, 95% CI = 1.3-53), age above 44 years (OR = 20, 95% CI = 4.1-83), CD4 < 500 (OR = 6, 95% CI = 1.1-26), use of HAART therapy (OR = 12, 95% CI = 1.0-156), and time on HAART therapy (trend p = 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ.

The objective of the present study was to assess the presence of human papilloma virus (HPV) in HIV-infected women, with comparison between the Papanicolaou cytologic technique and the molecular PCR technique, as well as to determine the type of HPV, to measure cellular immunocompetence and to identify the presence of risk factors for the acquisition of HPV infection. Thirty HIV-infected women were selected. Vaginal and endocervical samples were collected from 27 of them. The smears were examined by 3 experienced cytologists to diagnose the presence of HPV by the Papanicolaou technique and the results were compared to HPV detection and typing by PCR. HPV-infected patients were interviewed in order to identify the presence of risk factors for the acquisition of the virus. Eight of the 27 patients analyzed (29%) presented HPV in endocervical samples submitted to PCR, 6 of them (75%) presented HPV involving a high risk of development of cervical cancer. For 5 of these patients, the cytologic diagnosis was not confirmed by PCR. When cellular immunocompetence was related to HPV infection, PCR revealed a diagnosis of HPV in 37.50% of the patients at intermediate risk for HPV infection and in 83.33% of the patients at high risk for HPV infection. These immunologically compromised HPV-infected patients are at higher risk of developing cervical neoplasia. We showed here that PCR is adequate for HPV detection and that, if only the Papanicolaou method is used for the follow-up of these patients, we will not provide good prevention of cervical cancer.

Objective: To estimate the incidence and duration of cervical human papillomavirus (HPV)-6, HPV-11, HPV-16, and HPV-18 infections in a population of young American women., Methods: The study population consisted of U.S. women who at baseline were 16 to 23 years of age, reported zero to five lifetime sexual partners, never having been pregnant, and never having had a prior abnormal Papanicolaou test and were enrolled in the placebo arm of a randomized multicenter clinical trial of a HPV-16 L1 virus-like particle vaccine. Women underwent type-specific endocervical/ectocervical swab HPV DNA testing at approximately 6-month intervals for up to 48 months of follow-up. To contribute person-time in the analyses of type-specific HPV incidence, a woman must have had at least three satisfactory swab specimens available and been negative for the relevant HPV type (HPV-6, HPV-11, HPV-16, or HPV-18) on her first two trial swabs. The duration of incident HPV infections was estimated using Kaplan-Meier survival analysis methods., Results: Person-years of exposure ranged by type-specific analysis from 2,645 to 3,188, with an incidence rate per 100 person-years of 3.6 for HPV-6, 0.4 for HPV-11, 5.4 for HPV-16, and 2.1 for HPV-18. With censoring at the time of treatment for cervical intraepithelial neoplasia, where done, the mean duration of incident infections was 9.3, 8.4, 18.2, and 16.4 months, respectively, for HPV-6 (n = 103), HPV-11 (n = 13), HPV-16 (n = 142), and HPV-18 (n = 62). When the duration of HPV infections was truncated at the time of cervical intraepithelial neoplasia detection (any grade), where applicable, mean duration figures were 8.4, 8.1, 14.0, and 15.1 months for HPV-6, HPV-11, HPV-16, and HPV-18 infections, respectively., Conclusions: Previous studies of the mean duration of cervical HPV infection have been based on prevalent infections and/or featured relatively short duration of follow-up. This study tested women for HPV infection over a period of up to 48 months and observed a mean duration of incident HPV-16/HPV-18 infections approximately twice that of HPV-6/HPV-11.

Type-specific persistent infection with Human Papillomavirus (HPV) is a significant risk factor for the development of cervical diseases. Persistent infection could be further refined by a sequencing approach to detect early cervical lesions that are at high risk of developing an invasive squamous cervical cancer. The aim of the present study is to investigate the clinical utility of detecting mRNA transcripts of HPV oncogenes E6/E7 by using a Real-time NASBA technology (mRNA test) and to identify women with low-grade cytological disease but with an increased risk of developing high-grade cervical abnormalities or invasive squamous cervical cancer. Our preliminary results show that E6/E7 is detected in only a subset of HR-HPV-positive cases. Since viral persistence is considered to be the true precursor of neoplastic progression, only the detection of E6/E7 mRNA can identify the infection which is more likely to persist and induce neoplasia in future. For these reasons we believe that this test would be useful for the characterization of women with HR-HPV DNA positivity who should be effectively treated because at high-risk of developing a high grade cervical lesion or an invasive squamous cervical cancer.

Objective: To investigate the association between HPV16 infection, E6/E7 variations and the cervical lesions., Methods: HPV subtypes were detected by using flow-through hybridization technique, E6/E7 gene was extracted from cervical lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid pMD18-T and sequenced., Results: HPV 16 was the most common type which accounted for 33.3% (154/463), the HPV16 infection rates increased with the severity of cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased with the severity of cervical lesions (P < 0.05)., Conclusion: HPV 16 was the most common type in women with cervical lesions in Beijing, D32E/N29S variant associated with the cervical lesions.

Large loop excision of the cervical transformation zone (LLETZ) is a well-established treatment for high-grade cervical intraepithelial neoplasia. It has even been postulated that LLETZ is responsible for the elimination of the infectious agent, human papillomavirus (HPV), causing the lesion. Most studies on HPV detection after LLETZ have focused on the persistence of high-risk (hr-) HPV to identify women at risk for residual or recurrent disease. Therefore, the appearance and significance of hr-HPV types newly detected after surgical treatment has not been studied extensively so far. The presence of hr-HPV in 85 high-grade squamous cervical LLETZ biopsies and in the first follow-up smear was determined. In 80 (94%) of the LLETZ biopsies hr-HPV was detected in contrast to 30 (35%) hr-HPV positive follow-up scrapes. Twenty of the 80 hr-HPV positive women (25%) had the same hr-HPV genotypes in their follow-up cervical smears as was found in the corresponding biopsies. In the follow-up smear of 13 women a new hr-HPV genotype was detected and HPV 18 was newly detected in 8 of them. The remarkably high presence of newly detected HPV 18 genotypes may argue for a release or re-activation of this virus from proximal layers of the cervical canal incised during surgery.

Objective: To ensure complete reliability in the detection of hyman papillomavirus using either Specimen Transport Medium (Digene Inc., Gaithersburg, Maryland, U.S.A) or an alcoholic cell preservative., Study Design: In order to compare both media, we adjusted the cell content of specimens and optimized the denaturation duration to avoid chemiluminescence inhibition., Results: We validated this protocol in 2 groups of 90 patients, leading to agreement of 100% in both positive and negative tests. This was confirmed using linear regression curves. We demonstrated that any change in the Digene protocol, especially the use of other preservatives, should be carefully evaluated since it may interfere with DNA denaturation and hybridization and the chemiluminescence signal. The main risk was obtaining false positive responses from nonspecific DNA hybridization and false negative ones because of chemiluminescence signal inhibition., Conclusion: It is necessary to take into account preservative characteristics when a new protocol is under validation.

Background: Human papilloma virus (HPV) is one of the most frequently observed sexually transmitted infections. The study' purpose was to investigate the relation between a mother's gynecological history and the local status of her child with recurrent respiratory papillomatosis (RRP)., Methods: Forty-two patients enrolled in a prospective multicenter study between 1983 and 1990. The study included patients with juvenile-onset and adult-onset RRP. All patients underwent surgery and treatment with alpha-interferon. Thirty-eight patients were followed up until 31.01.2006. Twenty-five mothers of these patients participated in a parallel prospective study of genital HPV infection. In 1989-1990, all received a routine gynecological examination, an expanded colposcopy, a Pap smear, and a cervical biopsy. The mothers were followed up until February 2006., Results: 74% of patients with RRP were the first-born children. Five (20%) mothers had condylomata acuminata, newly diagnosed during pregnancy. Indicators of HPV infection such as koilocytes, koilocytotic dysplasia and condyloma acuminatum were revealed cytologically in 17% of cases and histologically in 71.4% of cases. Six (24%) of mothers had had a hysterectomy. HPV type 11 was prevalent in the children of mothers who had had a hysterectomy. Among the patients with juvenile-onset RRP, the death rate from squamous cell carcinoma of the lung was significantly higher in those patients whose mothers had a hysterectomy (p=0.028)., Conclusions: Mothers of patients with RRP demonstrated cytological and histological indicators of HPV infection in the genital tract. An adverse outcome of the disease in the child was associated with adverse gynecological history in the mother.

Cervical cancer (CC) and its precursor lesions (CIN) are unique in that we can study the natural history of one disease at two different levels; i) by assessing the clinical lesions, and ii) by analysing the viral events of human papillomavirus (HPV) infections, their prime etiological agent. In this review, we are interested in mechanisms and predictors of clearance of oncogenic HPV infections in the uterine cervix. The outcome (natural history) of CIN has been well established by a large number of prospective cohort studies covering over 25,000 patients, and the figures for regression, persistence and progression are well established. The outcome of HPV infections is far more complex with at least six distinct patterns being demonstrated in long-term cohort studies. There is little doubt that the mechanistic explanation for HPV clearance is by specific immunological reactions, where competent humoral and cell-mediated immune mediators are needed. To understand this process in detail still necessitates a substantial amount of clinical and laboratory research, however. In general, HPV outcomes follow the pattern where a dynamic balance exists between incident infections and virus clearance. Following a rapid accumulation of incident infections after onset of sexual activity (women < 20 years of age), there is a transition of this balance in favour of virus clearance soon after age 25. This explains the constantly declining age-specific prevalence of HPV infections until menopause. Failure to eradicate the virus at postmenopause is not uncommon, however, explaining the deep second peak in HPV prevalence now reported in many different populations. The importance of HPV clearance/non clearance (= persistence) has been recognised recently, and the number of studies addressing these issues has increased substantially during the past few years. The data are now rather unanimous concerning the times and rates (usually expressed per 1,000 women/months at risk, WMR) of HPV clearance. On the other hand, data are still incomplete and in part inconsistent as to the cofactors that regulate these events. A wide variety of variables have been explored as potential co-determinants and/or predictors of HPV clearance, as reviewed in this communication. Until now, all efforts attempting to identify suitable biomarkers as such predictors, have been disappointing, but fortunately, this is a largely unexplored area as yet. Similarly, data on the two extremes of life, i.e., early infancy and postmenopause, are still far too fragmentary to enable creating a comprehensive view, how these viral infections behave in early life, and what makes many women incapable of clearing their virus at postmenopause. Both issues are of utmost importance and have widespread clinical implications; we need to know how and why some infants and children contract HR-HPV infections well before the onset of their sexual activity, to be able to select the proper targets for prophylactic HPV vaccination. Similarly, we need to know why some women over 55 years of age are likely to remain HR-HPV carriers, while the vast majority successfully clears their infection well before the menopausal age. Early detection of cervical cancer precursors among these elderly HR-HPV positive women past the usual age of organised screening remains a major challenge also in the future.

Background: The results of the UK pilot studies were encouraging with respect to the introduction of Human Papillomavirus (HPV) testing as a means to improve the management of low-grade cytological abnormalities. However, several important unresolved issues related to HPV triage remain, two of which are: what type of HPV test should be used and what age group should be targeted., Objectives: To perform an evaluation of two commercial HPV detection tests and to correlate disease persistence and clearance with age and HPV status by the two tests., Study Design: We performed an evaluation of two commercial HPV tests in a cross-sectional analysis of 322 cervical cytology specimens with low-grade abnormalities. A subset of these specimens were then examined longitudinally, in order to correlate disease persistence and clearance with age and HPV status by the two detection tests., Results: The two tests performed similarly with respect to the longitudinal identification/prediction of high-grade cervical disease. Age did not appear to be a factor in determining which cases went on to manifest high-grade disease within 3 years of a low-grade result (p=0.678)., Conclusions: This study weakens the case for age-adjusted HPV triage of low-grade cervical abnormalities.

Objective: To investigate the status of genital infection as well as distribution of types of human papillomavirus (HPV) in women in Shenzhen and provide population data for the future vaccine intervention on cervical cancer., Methods: Women with age between 15 and 59 years were selected in cluster stratified sampling from Huaqiaocheng community, Nanshan district, Shenzhen and received a population-based cervical cancer screening. After consent, every woman was interviewed by using questionnaire and tested by liquid-based cytology and HPV DNA (hybrid capture 2 and gene chips typing) separately., Results: Totally 1 137 women were screened. The rate of high risk HPV of hybrid capture 2 test (14. 0% ) was higher than gene chips typing test (9. 8%) (chi(2) = 27. 198, P < 0. 001) ; the consistency of the two tests was acceptable ( kappa = 0. 498, P < 0. 001). The rates of low risk HPV types and other types of gene chips typing test in this population were 1. 9% and 0. 2% respectively. The percentages of HPV 16, 18 and 58 in HPV positive women were 29. 7% , 18. 9% and 18. 9%. The rates of different age group of low risk HPV were 1. 4% (17-34), 1. 7% (35-44) and 3. 2% (45-59) , respectively., Conclusions: HPV 16, 18, and 58 are the most popular types in the study population. The differences of infection rates of high risk HPV are due primarily to the variation of HPV16 distribution among age-specific population. The chances of being affected by low risk HPV will increase with age.

Objective: Liquid-based cytology (LBC) for cervical screening is becoming increasingly used. Together with SurePath LBC, various collecting devices can be utilized, among which the Cervex-Brush is the most widely used. The new Rovers Cervex-Brush Combi combines the advantages of the Cervex-Brush with the EndoCervex-Brush increasing sampling of the endocervical canal. The objective of this study was to analyse and to compare the Cervex-Brush Combi with the Cervex-Brush for the collection of squamous and endocervical cells, human papillomavirus (HPV) typing/quantification and disease detection in SurePath LBC., Methods: Using either the Cervex-Brush or the Cervex-Brush Combi 100 consecutive SurePath LBC samples were collected using each brush type. All 200 slides were read by the FocalPoint and screened by guided screening using slide wizards. The viral load of HPV type 16 E7, 18 E7, 31 E6, 33 L1, 33 E6, 35 E4, 39 E7, 45 E7, 51 E6, 52 L1, 52 E7, 53 E6, 56 E7, 58 L1, 58 E6, 59 E7, 66 E6 and 68 E7 was determined using a TaqMan-based real-time quantitative PCR analysis., Results: The mean number of sampled squamous cells did not differ between the two brush types (54 963 versus 54 595 cells). The use of the Cervex-Brush Combi, however, resulted in a two- to threefold increase in the number of sampled endocervical cells (P < 0.00001). Using the Cervex-Brush Combi slightly more lesions were detected (three versus two low-grade squamous intraepithelial lesions), and resulted in the detection of more atypical squamous cells of undetermined significance (six versus three). In the Cervex-Brush group, 60% (3/5) of abnormal smears were positive for oncogenic HPV types, whereas 66.7% (6/9) of abnormal smears in the Cervex-Brush Combi group tested positive. The median HPV viral load for samples taken with the Cervex-Brush Combi was 0.1825 copies/cell and was significantly higher than in samples taken with the Cervex-Brush (0.0042 copies/cell) (P = 0.02)., Conclusion: Sampling with the Cervex-Brush Combi resulted in the collection of the same amount of squamous cells, but in a two to threefold harvest of endocervical cells. This led to the detection of a higher viral load for oncogenic HPV and an increase in the number of detected abnormal smears.

Human papillomavirus (HPV) is an etiologic agent for both oropharyngeal and cervical cancers, yet little is known about the interrelationship between oral and cervical HPV infections. Therefore, we compared the prevalences and type distributions of oral and cervical HPV infections and evaluated infection concordance in a cross-sectional study within the Women's Interagency HIV Study cohort. Oral rinse and cervical-vaginal lavage samples were concurrently collected from a convenience sample of 172 human immunodeficiency virus (HIV)-positive and 86 HIV-negative women. HPV genomic DNA was detected by PGMY09/11 L1 consensus primer PCR and type specified by reverse line blot hybridization for 37 HPV types and beta-globin. Only 26 of the 35 HPV types found to infect the cervix were also found within the oral cavity, and the type distribution for oral HPV infections appeared distinct from that for cervical infections (P<0.001). Oral HPV infections were less common than cervical infections for both HIV-positive (25.2% versus 76.9%, P<0.001) and HIV-negative (9.0% versus 44.9%, P<0.001) women. Oral HPV infections were more common among women with a cervical HPV infection than those without a cervical HPV infection (25.5% versus 7.9%, P=0.002). The majority of women (207; 93.7%) did not have simultaneous oral and cervical infections by the same HPV type; however, the number of women who did (14; 6.3%) was significantly greater than would be expected by chance (P=0.0002). Therefore, the oral and cervical reservoirs for HPV infection are likely not entirely independent of one another.

Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for approximately 40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic alpha3/alpha15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (alpha9/alpha11/alpha7/alpha5/alpha6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (>54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related alpha9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with alpha7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions.

Introduction: HPV infection has a prime etiologic role in development and progression of cervical cancer, one of the most frequent forms of cancer among women in developing countries. This study was designed to determine the most prevalent HPV genotypes in women with normal and abnormal cervical cytology in Iran., Materials and Methods: Samples from134 patients, including 127 who attended gynecology clinics and 7 with solid cervical tumors were used. All 127 patients underwent routine Pap tests for cytological evaluation and at the same visit a sample of cervical epithelial cells was obtained by scraping the cervix osteum. In each case HPV infection was primarily evaluated by PCR using GP 5/6 primers and then subtyping was performed in proved infected samples with specific primers for HPV 16, 18, 31, 33, 11 and 6. After cytological evaluation, 50 patients with abnormal Pap tests were categorized as the abnormal group and the remaining 77 patients as the normal group., Results: In the normal group, HPV infection was established in 10 cases (13% infection rate), while 30 HPV positive cases were discovered in the abnormal group (60% infected). The most prevalent genotypes among the infected samples were HPV 16 (76%), HPV18 (12.7%) and HPV11/6 (8.5%). Moreover, all 7 tumor samples were positive for HPV general primers of which, 5 samples were infected with HPV 16, two were co-infected with HPV16,18 and HPV16,31 genotypes and one was infected with HPV 18., Conclusions: Infection with HPV 16 was found to be significantly higher in abnormal group in comparison with normal group (42% vs. 11.6%, P value <0.005), likewise HPV18 genotypes were proved to be more prevalent in abnormal group (8% vs. 0%, P value <0.05). No significant relation between other HPV genotypes and pathologic cervical changes was obtained. According to our study high rates of infection with HPV genotypes in sexually active Iranian women makes molecular investigation for HPV16 and 18 very essential in clinical approaches to patients with proven dysplasia in their screening tests and also for those patients with borderline (i.e. ASCUS) or incongruous pathology reports. Larger studies are required to determine the most appropriate vaccine with highest protection in Iranian women.

The objective of the present study was to evaluate the usefulness of molecular methodologies to access human papillomavirus genome in the genital tract. Samples from 136 women aged 17 to 52 years old obtained from the Dr. Sérgio Franco Laboratories between 2000 and 2001, were analyzed by the hybrid capture assay and amplified by PCR with generic primers MY09/MY11 and specific primers for types 16, 18, 31, 33, 35, 58. Viral genome was detected in 71.3% of the samples by hybrid capture and 75% by amplification. When cytopathology was used as a reference method for screening lesions, hybrid capture (p=0) and amplification (p=0.002) presented positive association. The 3 methods showed absolute agreement when cytopathology confirmed papillomavirus infection and high grade intraepithelial lesion. Disagreements occurred for 10 cases: seven inflammatory cases positive by PCR and negative for hybrid capture and 3 low squamous intraepithelial lesions positive for hybrid capture but negative for amplification. In conclusion, hybrid capture was shown to be sensitive and specific enough for use in clinical routines. Moreover, the evaluation of viral load values obtained by this method were shown to be related to the severity of the lesion and merit further studies to analyze the possible association with risk of progression to malignancy.

This article reports the HPV status and cervical cytological abnormalities in patients attended at public and private gynecological services from Rio de Janeiro State. It also comments the performance of each HPV DNA tests used. A set of 454 women from private health clinics was tested by routine Capture Hybrid II HPV DNA assay. Among these, 58.4% presented HPV and nearly 90% of them were infected by high risk HPV types. However, this group presented few premalignant cervical lesions and no invasive cervical cancer was registered. We also studied 220 women from low income class attended at public health system. They were HPV tested by polymerase chain reaction using My09/11 primers followed by HPV typing with E6 specific primers. The overall HPV prevalence was 77.3%. They also showed a high percentage of high squamous intraepithelial lesion-HSIL (26.3%), and invasive cervical carcinoma (16.3%). HPV infection was found in 93.1% and 94.4% of them, respectively. The mean ages in both groups were 31.5 and 38 years, respectively. In series 1, HPV prevalence declined with age, data consistent with viral transient infection. In series 2, HPV prevalence did not decline, independent of age interval, supporting not only the idea of viral persistence into this group, but also regional epidemiological variations in the same geographic area. Significant cytological differences were seen between both groups. Normal and benign cases were the most prevalent cytological findings in series 1 while pre-malignant lesions were the most common diagnosis in the series 2. HPV prevalence in normal cases were statistically higher than those from series 1 (p<0.001), indicating a higher exposure to HPV infection. Women from both samples were referred for previous abnormal cytology. However, socio-demographic evidence shows that women from series 1 have access to treatment more easily and faster than women from series 2 before the development of pre-malignant lesions. These data provides baseline support for the role of social inequalities linked to high risk HPV infection leading to cervical cancer. Broadly screening programs and the development of safe and effective vaccines against HPV would diminish the toll of this disease that affect mainly poor women.

The principal aims of this study were to test whether persistence of human papillomavirus (HPV) DNA is predictive of recurrent disease in women after surgical treatment for cervical lesions, to distinguish between persistent and newly acquired HPV infection, and to observe the effect of surgical treatment on levels of HPV-specific antibodies. A group of 198 patients surgically treated for low-grade and high-grade squamous intraepithelial lesions and 35 age-matched controls were monitored for 18 months at 6-month intervals. The presence of HPV DNA in cervical smears was detected by means of consensus polymerase chain reaction, and serum levels of HPV-specific antibodies to HPV types 16, 18, 31, 33, and 45 were measured. In ten patients positive for HPV type 16 in consecutive samples, the HPV 16 variants were identified using a polymerase chain reaction specific for the long control region. Data regarding demographics, risk factors for cervical cancer, and risks related to HPV exposure were collected through a patient questionnaire. Subjects persistently positive for HPV DNA were more likely to present with cytological and/or colposcopical abnormalities. A higher reactivity to HPV-specific antibodies was observed in these women at the 18-month follow-up visit. All ten patients with HPV 16 infection detected in consecutive samples showed persistence of either the same prototype or the same variant during the follow-up period. Risky sexual behavior and smoking were more common in patients than in controls. Persistent HPV infection as demonstrated by both HPV DNA detection and antibody detection appears to be a risk factor for the recurrence of pathological findings in women after surgery. An individually based approach to surgical treatment is an important factor in the outcome of disease at follow-up.

To examine the utility of human papillomavirus (HPV) DNA testing for the screening of cervical cancer and its precursors, a prospective cohort study was performed in which a total of 8156 women with a median age of 36 years were enrolled. Two smear samples scraped from the uterine cervix were served for Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive samples were further examined for HPV subtype using a DNA microarray chip. Women with cytologic abnormality or those with high-risk HPV DNA were further examined by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected in 11% of the general population, with higher prevalence of specific types, including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to have increased frequency of HPV infection. Notably, HPV DNA testing detected all 45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings were negative in 6 of these cases. It is of particular interest that CIN was commonly associated with multiple HPV types, while invasive cancers had a single type of HPV. In terms of both sensitivity and positive predictive value in detecting the CIN, HPV DNA testing is superior to cytology. However, most importantly, HPV DNA testing in combination with cytology significantly improved the efficacy to CIN screening.

Cervical cancer (CC) is the most common in Mexican female population. The human papillomavirus (HPV) 16 and 18 frequencies in worldwide may be different due to geographical distribution. We analyzed the prevalence of HPV types and determinated their association in cervical lesion in a Mexican population. One hundred fifty-nine normal cervical smears, 95 low-grade squamous intraepithelial lesions (LGSIL), 59 high-grade squamous intraepithelial lesions (HGSIL), and 108 CC samples of the patients were collected. HPV types were determined by sequencing. We detected 11 high-risk types, four low-risk types, three not determinated, and two probably high risk. HPV were present in 12%, 57%, 88%, and 92% from normal, LGSIL, HGSIL, and CC samples, respectively. HPV 16 was the most common in all cervical lesions (71.6% in CC). HPV 58 was present in 18.6% of HGSIL, and the HPV 18 in 4.6% of CC. The 76% of all detected viruses belong to A9 species branch. Control women showed high percentage of HPV high-risk infection, suggesting that this is a high-risk group. High frequency of HPV 16 compared with a low incidence of HPV 18 was observed. HPV 58 is frequently detected in HGSIL but low frequency is found in CC. These findings might be considered for HPV screening.

Laboratory markers of human papillomavirus infection have been recognized as relevant tools in programmes designed to reduce the burden of cervical cancer. The ongoing experience with these laboratory markers serves to confirm not only their negative predictive value (close to 100%) but also their positive association with developing or developed lesions. This aspect is particularly relevant in HIV-infected subjects who show an increased prevalence, incidence and severity of infections and lesions even in the era of efficacious control of their immunosuppression. Among the possible virus-related parameters proposed as relevant markers (viral persistence, load, expression, genomic integration capacity) we here analyse the informative value of human papillomavirus viral load measurement as a possible risk marker in this particular clinical setting.

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.

Objective: To determine the prevalence of HR-HPV DNA in ASC-US Pap smears following implementation of the Bethesda 2001 classification system., Methods: A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC-US Pap smears that underwent reflex testing for HR-HPV DNA were included. Additional clinical and demographic data were obtained from facilities within the US northeast region to evaluate the differences in ASC-US and SIL rates between the current and former Bethesda classification systems., Results: 550,000 Pap smears were collected during the study period. The HR-HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC-US Pap smears. Within the northeast region, the HR-HPV prevalence in ASC-US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8%) in patients 18-22 years old to 24.9% (95% CI = 23.1 to 26.8%) in patients age 29 and older. When comparing the two classification systems, significant increases in both ASC-H and SIL and decreases in ASC-US were appreciated after the institution of Bethesda system 2001., Conclusion: In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC-US Pap smear results. Additionally, the prevalence of HR-HPV in the ASC-US population was 40.8%, significantly lower than the rate noted in the ALTS trial under the Bethesda I classification system.

Objective: Analyse the performance of human papillomavirus testing with hybrid capture II on liquid-based CYTO-screen system for women diagnosed with atypical squamous cells of undetermined significance according to the age., Patients and Methods: Were included all women diagnosed with atypical squamous cells of undetermined significance for whom human papillomavirus testing was performed and cytological and histological procedures were available over a follow-up period of 6 to 18 months., Results: Human papillomavirus testing was performed in 3,047 patients, and results were compared to cytological and histological follow-up diagnosis in 1,880 cases (61.7%). The sensitivity for diagnosing cervical intraepithelial neoplasia was 93.3% in women less than 30 of age and 89.7% in women more than 30 of age. Specificity was 44.9% in women less than 30 of age and 64.4% in women more than 30 of age. Likelihood ratios confirmed these results as they show a low discriminatory power in case of positive result specifically in women less than 30 of age but an excellent performance in case of negative result., Discussion and Conclusion: The use of human papillomavirus testing after a diagnosis of atypical squamous cells of undetermined significance with the residual material of Cyto-screen system is a possible triage procedure to identify patients needing a colposcopy. Its specificity is better for women over 30.

Background: In this study, our prospective experience with a multimodal follow-up protocol is summarized, with special emphasis on predicting the treatment outcome of cervical diseases., Materials and Methods: Liquid-based cytology samples (ThinPrep) from 209 women exhibiting the whole spectrum of human papilloma virus (HPV)-related cervical diseases were investigated by cytology, PCR-based HPV genotyping and DNA cytometry pre-surgery. The first control cytology and type-specific HPV tests were performed at 3 months post-surgery., Results: The success rate of surgery was 95% in eradicating high-grade cervical disease and 90% in eliminating the baseline HPV genotype. Treatment failure was significantly correlated with baseline cytology (p=0.011), resection margin status (p=0.016) and HPV positivity at 3 months post-surgery (p=0.04). Multivariate logistic regression analysis showed that type-specific persistent HPV infection (p=0.028), baseline cytology (p=0.039) and histology (p=0.065) were independent predictors of residual cervical neoplasias., Conclusion: Our results showed that our multimodal surveillance protocol may help to individually assess the anticipated clinical outcome of cervical diseases post-surgery.

Background: Thai sex workers (SW) have high rates of sexually transmitted infections (STIs); however, detection and treatment is often complicated by accessibility to sensitive and accurate diagnostic tests. Self-sampling of women combined with molecular amplification techniques could help in accurate diagnosis, treatment and follow-up of such women. Detection of persistent high-risk human papilloma virus (HPV) in such populations could also be beneficial in identifying women who may need more frequent follow-up for cervical cytology screening. The current study aimed to examine the prevalence of HPV in this population and compare this with the lower-risk outpatient women (OPW) in Thailand., Methods: Four hundred and thirty OPW and 524 Thai SW were sampled by a self-administered tampon collection. Cells were extracted from tampons and, subsequently, women underwent routine vaginal examination for detection of other STIs. Detection of HPV was performed by polymerase chain reaction (PCR) using the L1 consensus primers, followed by L1 consensus probe using an in-house PCR-enzyme-linked immunosorbent assay (ELISA). All positive samples were typed using PCR-ELISA and type-specific oligonucleotide probes., Results: Overall, HPV was detected in 20/430 (4.6%) and 120/524 (22.9%) in OPW and SW respectively. Over 98% of samples produced a beta-globin signal, indicating adequately collected samples. Human papilloma virus typing probes detected HPV16 or 18 in 14% and 26% of the positive samples from OPW and SW respectively. HPV31, 33, 35 or 39 were detected in 19% and 12% and HPV45, 51 or 52 in 9.5% and 4% of positive OPW and SW patients respectively. Low risk HPV6 or 11 were detected in 1% and 4.9% of OPW and SW respectively., Conclusion: There was a significantly higher HPV prevalence in Thai SW than OPW, with the majority (21%) of positive samples containing the oncogenic HPV16 or 18 DNA. The results indicate that PCR could serve as a rapid and easy method for identification of women who require more frequent screening for cervical cancer.

Objective: To evaluate the clinical efficacy of flow-through hybridization and gene chip (HybriMax) on female low genital human papillomavirus (HPV) detection and to identify the most common HPV genotypes., Methods: Five hundred and ninety-one of 7520 women who received cervical cancer screening in China-Japan Friendship Hospital during Jun 2004 to May 2005 were selected for 21 genotypes HPV detecting by HybriMax, including 138 women with normal cytological diagnosis and 453 women with abnormal cytological diagnosis. The abnormal patients were classified into groups according to their histological diagnosis as chronic cervicitis, cervical intraepithelial neoplasia (CIN) I, II, III, cervical cancer and condyloma acuminata. Among them 413 women were tested with HC-II for 13 types of high-risk HPV, and 101 paraffin-embedded specimens from these 453 patients were detected for HPV16, 18 with in situ hybridization (ISH). The accordance of the results was compared. The infection rates of each HPV type for each group were calculated., Results: The total accordant rate of HybriMax and HC-II on 13 types of high-risk HPV detecting was 92.5% (382/413) and was 100.0% in group of cancer. The accordance was good, and the Kappa index (KI) was as below: overall 0.814, in normal group 0.750, in chronic cervicitis 0.781, in CIN I 0.755, in CIN II 0.619, in CIN III 0.548, in condyloma acuminata 0.800. The accordant rate of HybriMax and ISH was 89.1% (90/101), and KI was 0.766. The 10 most common genotypes were (in descending sequences): in normal group 16, 68, 18, 52, 58, 11, 53, 31, 39, 33; in abnormal group 16, 52, 58, 18, 33, 31, 81, 53, 68, 66, in cervical cancer 16, 18, 52, 58, 33, 66, 68, 31, 51, 53., Conclusions: HybriMax has good accordance to HC-II and ISH for HPV detection. It provides useful information on viral genotype and is more suitable for clinical use. The 6 most common genotypes in abnormal cytological group are 16, 18, 52, 58, 33, 31.

Background: Persistent infection with a subgroup of at least 15 high-risk human papillomavirus (HPV) genotypes is considered as a necessary although insufficient etiological factor in the development of cervical carcinoma. As a consequence, HPV testing has recently become an important part of the cervical carcinoma screening and detection algorithms., Aim of the Study: To evaluate the analytical performance of a recently developed polymerase chain reaction (PCR)-based Amplicor HPV test (Roche Molecular Systems) in comparison with the Hybrid Capture 2 HPV DNA test (hc2) (Digene Corporation) for the detection of 13 high-risk HPV genotypes. Inhouse consensus PGMY09/PGMY11 and CPI/IIg PCRs targeting two different HPV genes coupled with HPV genotyping were used as an HPV internal reference standard., Materials and Methods: In the retrospective evaluation, 550 cervical scrape specimens with previously established HPV status were included. Additionally, 312 cervical scrape specimens were tested prospectively for the presence of 13 high-risk HPV genotypes by both hc2 and Amplicor HPV test., Results: In the retrospective evaluation, the Amplicor HPV test results agreed almost completely with the HPV internal reference standard results. In the prospective evaluation performed on 312 samples, the concordant Amplicor and hc2 results were obtained in 85.9% of samples tested., Conclusion: In our hands, the Amplicor HPV test demonstrated high analytical sensitivity and specificity. The higher analytical specificity of Amplicor in comparison to that of hc2 can be considered clinically useful. Prospective studies with clinical endpoints are urgently needed to assess the clinical utility of the higher analytical sensitivity of the Amplicor HPV test for primary HPV screening and triaging patients with ASC-US.

Objectives: In this study, we are testing the hypothesis that human papillomavirus (HPV) positivity is correlated with chromatin texture in the cell. Interim analyses are important since this study involves 2000 patients and generates 6000 biopsy specimens that will be subjected to quantitative histopathological analysis and correlated to HPV positivity as measured by the Hybrid Capture II test (Digene; Gaithersberg, MD) and both HPV-DNA and mRNA by the polymerase chain reaction (PCR). The studies of optical technologies, from which we derive this sample, use the colposcopically directed and histopathologically classified cervical biopsy as the gold standard. In this report, we describe the results of an interim analysis of quantitative histopathology and chromatin texture as correlates of HPV infection using the cyto-savant system in cytologically and histopathologically negative specimens., Methods: A group of 1544 patients entered the optical technology trials, generating 3275 biopsies and 1544 Papanicolaou readings. Two hundred forty-eight patients were cytologically and histopathologically negative. Study pathologists reviewed histologic samples 3 times in a blinded fashion. Non-overlapping, quantitatively stained nuclei were selected from the samples by the pathologists. HPV testing was done using the PCR method and the Hybrid Capture II test. Statistical analysis involved the creation of a classification matrix using a linear discriminant analysis. The matrix was trained on HPV-positive cells by PCR. The analysis included the random creation of both a training set and a validation set that were classified based on the discrimination score obtained by correlating nuclear texture with HPV positivity., Results: The sensitivity of the classification was 52-54% and the specificity was 77-78%. Overall, a 68% predicted accuracy was achieved for both the training set and the test set. The agreement of a test and training set shows that the sets created randomly are indeed similar, and that the discrimination score worked equally well in both sets of cells. Once a cell-by-cell algorithm for HPV positivity was derived, HPV positivity was recalculated on the basis of cell-by-cell texture features. HPV positivity was then recalculated on both a per-biopsy basis and a per-patient basis. For HPV 16 and 18, the positivity rate was 70% on a per-biopsy basis and 73% on a per-patient basis., Conclusions: Although these results are preliminary, they suggest that texture features reflecting chromatin condensation may correlate with HPV positivity. The current sample is histologic, the analysis suggests that in a cytologic sample, HPV positivity could be detected or confirmed by texture features computed as part of an HPV-associated score. Additional biologic markers could be used as needed. While this study was performed on histologic samples, a study of cytologic samples would be more useful. Future studies will examine chromatin texture compared to HPV integration and mRNA HPV expression.

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.

To explore factors affecting human papillomavirus (HPV) prevalence in all grades of cervical neoplasia among Chinese women, 1,264 women with abnormal cervical cytology attending the gynaecologic clinics of 11 major medical centres in Taiwan. Patients were interviewed and underwent complete gynaecologic examination including colposcopy. Cervical scrapings were collected for HPV DNA detection by both Hybrid Capture-2 (high-risk probe) and L1 consensus PCR-reverse line blot. The prevalences of HPV in the four different diagnosis groups: (i) suspicious (n = 316), (ii) low-grade intraepithelial lesion (n = 474), (iii) high-grade intraepithelial lesion (n = 450), and (iv) cancer (n = 16), were 36.1%, 74.7%, 83.6%, and 100%, respectively. In the latter two groups, Patients less than 30 or 40 years old, respectively, tended to be infected more frequently with HPV than the older patients were. The main correlates of HPV prevalence were lifetime number of sex partners (odds ratio (OR) for two or more partners: 2.44; 95% CI, 1.44-4.15), vaginal douching after intercourse (OR for douching frequently: 1.44; 95% CI, 1.01-2.04), vitamin supplementation (OR for regular vitamin supplement: 0.71, 95% CI, 0.55-0.92), and performance of Pap smear tests (OR for never having a Pap smear performed: 2.22; 95% CI, 1.19-4.17). The risk for vaginal douching was augmented by the promiscuity of sex partners (OR of 3.19 (1.91-5.34)) and smoking (OR of 1.90 (1.15-3.13)), whereas vitamin supplementation reduced the odds ratio to 1.35 (0.85-2.15). The results of this study provide further evidence of the role of HPV in cervical carcinogenesis. The data also indicate the main areas of risk for the prevalence of HPV in cervical neoplasia in Chinese women living in Taiwan., ((c) 2005 Wiley-Liss, Inc.)

Background: In the last decade many studies have definitely shown that human papillomaviruses (HPVs) are the major cause of cervical carcinogenesis and, in the last few years, HPV testing has been proposed as a new and more powerful tool for cervical cancer screening. This issue is now receiving considerable attention in scientific and non scientific press and HPV testing could be considered the most important change in this field since the introduction of cervical cytology. This paper reports our prevalence data of HPV infection collected in the '90s, while a follow up of these patients is ongoing., Methods: For this study we used polymerase chain reaction (PCR) to search HPV DNA sequences in cervical cell scrapings obtained from 503 asymptomatic women attending regular cervical cancer screening program in the city of Genova, Italy. All patients were also submitted to a self-administered, standardized, questionnaire regarding their life style and sexual activity. On the basis of the presence of HPV DNA sequences women were separated into two groups: "infected" and "non infected" and a statistical analysis of the factors potentially associated with the infection group membership was carried out., Results: The infection rate was 15.9% and the most frequent viral type was HPV 16., Conclusion: Our HPV positivity rate (15.9%) was consistent to that reported by other studies on European populations.

Objective: To study the prevalence and association of human papillomavirus (HPV) infection in the cervix of pregnant women without visible signs of genital HPV infection undergoing cesarean delivery in the third trimester and to investigate a possible HPV transmission to the fetus., Methods: All women underwent cesarean delivery between 37 and 40 weeks of gestation. Cervical samples were taken prior to cesarean delivery. Furthermore amniotic fluid, placental tissue, and cord blood were sampled and polymerase chain reaction (PCR) or Hybrid Capture II test (Digene Corp, Beltsville, MD) was performed to detect HPV DNA., Results: We found that 56 (36.6 %) of 153 women were positive for HPV in the cervix. Logistic regression analyses showed a decrease of prevalence of HPV infection with increasing maternal age (P = .02). No HPV DNA could be detected in the amniotic fluid or cord blood, whereas eight placental specimens were positive for HPV DNA., Conclusion: The infection rate in women without clinical symptoms of HPV infection is high, but there was no HPV found in the amniotic fluid and in cord blood in women with subclinical infection in the third trimester.

To detect HPV in genital warts (Condylomata acuminata, CA) for infection rate and association of specific HPV types between males and females, and to provide support for the development of HPV vaccines, we designed HPV type-specific oligonucleotide primers to amplify DNA fragments encoding L1 viral capsule protein. SSP-PCR was conducted in duplication for each CA sample from male and female patients. DNA of TA-cloned HPV was used as positive control, and deionized H2O was used as negative control. A total of 22 clinical samples, 13 from males and 9 from females, was collected from patients diagnosed with CA at hospitals in Beijing and Handan. HPV viral DNA was amplified in all 22 samples analyzed, with 100% detection rate. TA-cloning and sequencing of the PCR products confirmed correct amplification of HPV type-specific fragments. Of the 13 samples from males, 5 were infected with HPV6, 6 with HPV11, and 2 with HPV6 + HPV11. Of the 9 samples from females, 3 were infected with HPV6, 2 with HPV11, and 4 with both HPV6 and HPV11 infection. In addition, high-risk types HPV16, HPV18, HPV33, HPV35, HPV45, HPV54, HPV56 and HPV58 were also detected in 4 female samples that were mixed with cervical cell debris during sample collection. However, no HPV types other than HPV6 and HPV11was detected in all CA-only samples in this study. We have established a sensitive and reliable laboratory procedure for HPV detection and classification. Using the method, we reached 100% detection rate of HPV in the CA samples. Our results confirm that HPV6 and HPV11 are primarily responsible for CA, and there is no specific association of HPV types between warts in males and females.

Management practices for low-grade cervical lesions identified on screening swabs have been modified by research on the HPV. The appropriate approach for low-grade lesions is particularly difficult to determine due to the potential risk of malignant transformation coupled with the cost implications of treating lesions which will heal spontaneously in the majority of patients. The diagnosis of these low-grade lesions can be improved by thin layer swabs which have a greater sensitivity than conventional swabs. The current consensus is that swab results should be expressed according to the Bethesda classification. Routine tests for HPV (Hybrid Capture II) should be reserved for patients with an ASC-US swab. Colposcopy is indicated if the swab is positive for a low-grade lesion followed by cytology if the colposcopy is normal. If there is no evidence of HPV, search for oncogenes can lighten the treatment regimen due to the high specificity of the test. If a low-grade histological lesion (CIN1) is proven, cytocolposcopic surveillance should be proposed, surgical resection being undertaken in colposcopy cannot be performed. Here again search for HPV oncogenes at one year is an interesting alternative if the examination is negative. These practices are applicable in adolescents and HIV- positive patients who are particularly exposed to HPV.

Background: Genital human papillomavirus (HPV) infections are generally accepted to be sexually transmitted, but studies of HPV infections in sex partners are limited. We investigated HPV type-specific concordance and viral load in 238 heterosexual couples. Women with cervical intraepithelial neoplasia were the index patients in these couples., Methods: GP5+/6+ polymerase chain reaction (PCR), followed by reverse-line blot analysis, was used for the detection of 45 HPV types in cervical and penile scrape samples. Viral loads were subsequently determined in scrape samples positive for HPV types 16, 18, 31, and 33 by LightCycler-based real-time PCR assays., Results: A total of 89.9% of the women and 72.9% of their male partners were HPV positive. Predominantly high-risk HPV types were found in persons of both sexes, but infections with multiple and non-high-risk HPV types were more common in men. Of the HPV-positive couples, 57.8% of the men had the same HPV type as their partners; this rate was significantly higher than that expected by chance (P < .001). Moreover, these HPV-concordant men had higher penile scrape viral loads than did the non-HPV-concordant men. For HPV type 16-positive women, higher cervical viral loads were predictive of presence of HPV type 16 in their sex partners., Conclusions: In sexually active couples, HPV type concordance was more prevalent than expected by chance and was associated with increased viral loads. These data provide biological support for HPV transmission between sex partners.

This is an audit of a new technique to improve the colposcopy service. Samples were tested for high risk HPV DNA using Digene Hybrid Capture II. Sixty-four percent of the sampled women under 30 had detectable high risk HPV DNA, decreasing to 44% in 30--39 year olds and to 27% in women over 40. High risk HPV prevalence increased with severity of cytology, although 22% with normal colposcopy had detectable high risk HPV. Of those women treated for cervical dysplasia, 83% had detectable high risk HPV prior to treatment, compared to only 32% afterwards. The audit has shown that high risk HPV testing has considerable discriminatory value. It has been integrated successfully into the service, particularly to manage low grade cervical abnormalities and to add valuable information following treatment for cervical dysplasia. Results need to be interpreted alongside colposcopy, cytology, and histology, and care must be taken in the interpretation of a single high risk HPV result., ((c) 2005 Wiley-Liss, Inc.)

Women seeking sexually transmitted disease (STD) services are at high risk of human papillomavirus infections. Cervical cytological screening with Papanicolau staining (Pap smear) is not consistently offered at public STD clinics. We reviewed Pap smear results on a series of 1000 female STD clinic attendees, abstracted demographics, risk behaviours and STD diagnosis from the clinical record and tested for associations with abnormal Pap smear. In all, 5.7% of the satisfactory specimens (56/993) were abnormal; increasing age category, genital warts, and chlamydia infections were independently associated with an abnormal Pap smear in multivariate analysis. Routine Pap smear screening provided satisfactory results in the STD clinic and, where population-based programmes are not available, should be fully integrated into public STD care, (particularly in settings serving younger women).