Cervical intraepithelial neoplasia in HIV seropositive patients

In order to assess the frequency of cervical intraepithelial neoplasia (CIN) in a high risk population, 32 women infected with human immunodeficiency virus (HIV), with no AIDS-related symptoms, underwent colposcopic, cytologic and histologic examinations of the uterine cervix. In seven cases (21.9%) cervical smears showed dysplasia and in nine cases (28.1%) histologic evaluation indicated CIN. No invasive carcinomas were observed. In seven of the nine women CIN was associated with lesions due to human papillomavirus infection (HPV). These data confirm that HIV-positive women are at increased risk for developing neoplasias in the lower genital tract and are in need of regular and careful cytologic and, in particular, colposcopic and histologic examinations.     

Inducible nitric oxide synthase (iNOS)-like immunoreactivity in argyrophilic, tau-positive astrocytes in progressive supranuclear palsy

The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as 相似文献   

Early regression of cervical lesions in HIV-seropositive women receiving highly active antiretroviral therapy

OBJECTIVE: Advanced HIV disease is associated with a high prevalence of cervical squamous intra-epithelial lesions (SIL) and of infection with oncogenic human papillomavirus (HPV) genotypes. Triple-combination antiretroviral therapy results in decreased plasma HIV viral load, increased CD4 cell counts and partial restoration of immune functions in patients with severe HIV disease. This study investigated the outcome of SIL in HIV-seropositive women undergoing triple combination antiretroviral treatment. METHODS: Forty-nine women who started triple-combination antiretroviral therapy, including a protease inhibitor, were examined prior to and after a median 5-month treatment. We collected cytological, colposcopic and histologic data and assessed the presence of HPV DNA in cervical smears by PCR and Southern blot hybridization (SBH). RESULTS: The prevalence of SIL decreased from 69 to 53% during follow-up (P < 0.0001). Among 13 women who initially presented with high-grade SIL, conversion to lower grade was observed in two women and a full regression to normality was observed in one. Cytology also returned to normality in nine out of 21 women who initially presented with low-grade SIL. The high prevalence of HPV infection as detected by SBH and PCR was similar at the first and second examinations and the same high-risk viral genotypes were identified at both examinations in all infected patients but one. There was a higher increase in absolute CD4 cells in the subgroup of patients whose lesions regressed (99 versus 50 x 10(6)/l, P=0.03). CONCLUSION: Our observations demonstrate that active antiretroviral therapy may result in a reduced prevalence of cervical squamous intra-epithelial lesions despite the absence of clearance of HPV infection.     

Genomic variation of human papillomavirus type 16 and risk for high grade cervical intraepithelial neoplasia

BACKGROUND: Epidemiologic studies have demonstrated strong and consistent associations between the detection of human papillomavirus (HPV) type 16 DNA and the risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. However, HPV16 is also the most common type of HPV in the normal population, and only a minority of women with HPV16 infection develop cervical cancer. Studies of genomic heterogeneity in HPV16 have demonstrated the presence of multiple variant forms in all human populations examined to date. It is conceivable that the natural variants of HPV16 in a given population may not have the same biologic behavior. PURPOSE: This study was designed to determine the association between natural variants of HPV16 and the risk of biopsy-confirmed CIN 2 or 3, the most important precancerous lesions of the uterine cervix. METHODS: Prospective studies were conducted among 1) women attending a university and 2) women presenting to a sexually transmitted disease clinic. Subjects were eligible for inclusion in this investigation if the initial cytologic findings did not reveal CIN 2-3 and HPV16 DNA was detected by means of a polymerase chain reaction (PCR)-based method in one or more cervical or vulvovaginal samples. Eligible subjects were followed every 4 months with cervical Pap smears and colposcopic examinations. Women were referred for biopsy if cytology or colposcopy suggested CIN 2-3. Two groups of HPV16 variants, prototype-like and nonprototype-like, were determined by means of single-strand conformation polymorphism (SSCP) analysis of PCR products from the noncoding region of the viral genome. Representative SSCP patterns from HPV16 variants were further characterized by direct DNA sequencing of the PCR products. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated by Cox regression analysis. RESULTS: Prototype-like variants accounted for 79% of the HPV16 detected in university students and 86% of the virus detected in patients presenting to the sexually transmitted disease clinic. CIN 2-3 was confirmed by biopsy in nine of 57 HPV16-positive women attending the university and in 10 of 66 HPV16-positive women presenting to the sexually transmitted disease clinic. Among university students, those with HPV16 nonprototype-like variants were 6.5 (95% CI = 1.6-27.2) times more likely to develop CIN 2-3 than those with prototype-like variants. A similar association was observed among women presenting to the sexually transmitted disease clinic (RR = 4.5; 95% CI = 0.9-23.8). CONCLUSIONS: This study suggests that the risk of developing CIN 2-3 is not the same with all variants of HPV16 and that nonprototype-like variants confer a greater risk compared with prototype-like variants. The important genomic differences underlying this increased risk of CIN 2-3 remain to be determined.     

Cervical cytology findings in women infected with the human immunodeficiency virus

It has been suggested that immunocompromised, HIV-infected patients are at risk of developing HPV infection and SIL. The well documented role of HPV and SIL in cervical carcinogenesis should lead to frequent, careful evaluation of HIV infected women. Forty-four cervical smears from 23 patients (20 HIV and 3 AIDS) were reviewed. While 11 of the 23 patients produced negative smears, 11 had abnormal cytological findings on at least one occasion. Sixteen smears (36 percent) from 10 patients (43%) showed evidence of HPV and/or SIL. Two smears (two patients) were assigned to the benign epithelial atypia category. (One of these showed keratosis which may indicate HPV infection.) Six smears (three patients) represented either a severe Trichomonas, fungal (Candida sp.), or Herpes infection. Three smears were deemed unsatisfactory for diagnosis due to severe acute inflammation or obscuring blood. Five biopsies were available. In four, histologic findings supported the original cytologic diagnosis. One patient with a negative smear had a biopsy showing condyloma. This study further supports an association of HPV and/or cervical dysplasia with HIV. Careful evaluation and follow-up of HIV-infected women is essential.     

Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA

BACKGROUND: Knowledge about the natural course of HPV infection is still limited. In this study we investigated the presence of HPV DNA after treatment and clinical clearance of infection. METHODS: Eighty-two women treated for genital HPV infection at the STD clinic in Uppsala were consecutively selected for the study. After treatment with podophyllotoxin, and in some cases laser vaporization, a cell sample was taken at the follow-up visit 6-12 months after clinical clearance of the lesions as evaluated by colposcopy. Samples were analysed with PCR to detect HPV DNA. As a reference group, women treated for cervical intraepithelial neoplasia (CIN) with laser surgery, either with cone biopsy or vaporization, were followed-up after 6 months for the presence of HPV DNA. RESULTS: Six to 12 months after clinical clearance of HPV infection, 39 (48%) of the women showed detectable HPV DNA in cell samples from the cervix. Of these, 26 (67%) were found to harbor high risk HPV, six (15%) low risk, and seven (18%) either had more than one HPV type or HPV that could not be classified. All but three of the women treated for CIN (90%) were negative for HPV DNA. CONCLUSION: After clinical clearance of genital HPV infection half of the women had detectable HPV DNA. This does not necessarily imply that transmission to a new partner may occur, but indicates this possibility. Only 10% of the CIN treated women harbored HPV DNA in the cell samples in spite of showing high risk HPV infection before treatment.     

Immunoglobulin G responses against human papillomavirus type 16 virus-like particles in a prospective nonintervention cohort study of women with cervical intraepithelial neoplasia

BACKGROUND: Infection with cancer-linked human papillomavirus (HPV) types such as HPV type 16 (HPV16) is the most important risk factor in the development of cervical cancer. It has been shown that immunoglobulin G (IgG) antibody responses against HPV16 virus-like particles (VLPs) are specifically associated with genital HPV16 infection. PURPOSE: The aim of this study was to determine the temporal relationships between the presence of HPV16 VLP-specific IgGs, HPV16 infection patterns, and the course of premalignant cervical disease. METHODS: Plasma samples from 133 women who had been diagnosed originally with mild to moderate cervical dyskaryosis and enrolled in a prospective non-intervention cohort study conducted in Amsterdam, The Netherlands, from 1991 through 1996 were analyzed for the presence of HPV16 VLP-specific IgGs by use of an enzyme-linked immunosorbent assay. A detailed analysis was performed on 43 women with different HPV16 infection patterns during a follow-up period of 10-34 months. Progression or regression of cervical intraepithelial neoplasia (CIN) lesions was monitored by cytologic and colposcopic testing at intervals of 3-4 months. HPV typing in cervical smears was performed by use of a polymerase chain reaction-based assay. Statistical analysis of the serologic data was performed by use of the Mann-Whitney U test or 2 x 2 table analyses. RESULTS: The presence of HPV16 VLP-specific IgGs in the plasma of the patients was found to be associated with the presence of HPV16 DNA in the cervical smear. Significantly higher proportions of patients with persistent HPV16 infections (i.e., who were polymerase chain reaction positive in three to 11 consecutive tests) than of patients with cleared HPV16 infections were found to be positive for the presence of HPV16 VLP-specific IgGs (18 [69.2%] of 26 versus nine [28.1%] of 32, respectively; P = .003). HPV16 VLP-specific IgGs were consistently detected in all women (n = 11) who were persistently HPV16 DNA positive during follow-up and whose disease ultimately progressed to CIN III (histologically diagnosed severe dysplasia or carcinoma in situ). CONCLUSION: HPV16 VLP-specific IgG responses are present in the plasma of a majority of patients with persistent HPV16 infections and histologically confirmed high-grade lesions but only in a smaller subset of patients with cleared HPV16 infections and either normal cervical histology or low-grade CIN lesions. IMPLICATIONS: These results suggest that HPV16 VLP-specific antibodies are not responsible for the clearance of virally induced CIN lesions but that they might, in patients with persistent HPV16 infections, be indicative of an increased cervical cancer risk.     

Regional distribution and incidence of human papillomavirus infections among heterosexual men and women with multiple sexual partners: a prospective study

OBJECTIVE: To assess prevalence, incidence and potential risk factors of human papillomavirus (HPV) infection among heterosexual men and women with multiple partners and to identify niches of HPV-infection. DESIGN: A prospective study of heterosexual men and women with multiple partners attending an STD clinic as participants in a study on HIV from May 1988 until January 1991. Routine STD examination and physical examination using colposcopy were performed, interviews with standardised questionnaires were administered. Specimens for HPV DNA detection by polymerase chain reaction were collected from multiple sites of the genital, anorectal and oral regions. In women cervical cytology was performed. SETTING: The STD Clinic of the Municipal Health Service of Amsterdam. PARTICIPANTS: 162 women and 85 men entered the study, 110 women and 48 men were followed up. RESULTS: At entry of the study 37 (23%) women and 24 (28%) men were found positive for HPV DNA at any site. Only in one woman was oral presence of HPV DNA found during follow-up. Abnormal cervical cytology was observed in four women. In multivariate analysis, diagnosis of condylomata [odds ratio (OR) 5.61, 95% confidence interval (CI) 1.86 to 16.90)], reporting genital dermatological abnormalities (OR 3.72, 95% CI 1.38 to 9.99) and age (OR per year 0.93, 95% CI 0.88 to 0.99) predicted independently the presence of HPV DNA in women at entry of the study. In women 59 of the 99 (60%) HPV infections were observed in the genital region and 40% in the anorectal region: in men these figures were 65% and 35%, respectively. The incidence of HPV infection was 47.1 and 50.5 per 100 person-years for women and men respectively. At least 20/99 (20%) infections in women were intermediate or long persistent and only 3/48 (6%) HPV infections in men (P = 0.03). No risk factor for persistency could be determined, either in women or in men. CONCLUSIONS: HPV infection was found to be a multicentric genital and/or anorectal event both in women and men. The oral presence of HPV DNA was detected only once in one of the participants. In women persistent HPV infection was more common than in men. Independent predictors for presence of HPV DNA in women were diagnosis of condylomata acuminata, reporting genital dermatologic abnormalities and age. Incidence of HPV infection in women turned out to be 47.1 infections per 100 person-years and for men 50.5 per 100 person-years.     

Detection of human papillomavirus DNA and clinicopathological study of vulvar human papillomavirus infection

We studied 217 vulvar HPV infection patients by clinically, pathologically, and virologically. From 90.6% of the cauliflower-like vulvar lesions and 29.7% of the papillomatous and finger-like lesions, we detected HPV 6/11 DNA by dot blotting hybridization. The patients in 90.0% of the cauliflower-like group and 9.8% of the papillomatous and finger-like group had a high risk factor to intercourse with different sex partners (P < 0.0001). The pathological characteristics, nature history, and response to treatment were different. According to clinical, pathological, and virological findings divided three types: vulvar HPV infection type 1 (or condylomata acuminata), vulvar HPV infection type 2, and vulvar HPV infection type 3.     

Submandibular gland excision: a five-year review

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

Allopurinol hypersensitivity syndrome: hypersensitivity to oxypurinol but not allopurinol

OBJECTIVE: We assessed the clinical, histological, and virological features of anogenital human papillomavirus (HPV) infection, according to their immune status in HIV-1 infected men, referred for an anogenital examination or treatment, in comparison with immunocompetent patients. METHODS: The study population comprised 33 HIV-1 infected heterosexual or homosexual men and 38 HIV negative men seen in a screening and treatment centre for anogenital HPV infections. All patients were examined with a colposcope. Biopsies were carried out on all subjects with anogenital lesions for histological studies and HPV detection by Southern blot. RESULTS: The HIV infected patients had a balanopreputial HPV infection in 70%, anal in 30%, and urethral in 37%, while HIV negative patients had balanopreputial lesion in 72%, anal in 26%, and urethral in 16%. Diffuse anogenital lesions were present in 33% of the HIV infected cases and in 10.5% of HIV negative cases (p < 0.02). Among the HIV infected patients, the genital HPV lesions were condylomatous in 67.5% of the cases and dysplastic in 57%. HIV negative patients had condylomatous lesions in 86% of the cases and dysplasic in 14%. The condylomatous lesions of HIV infected patients had a low grade malignant histological aspect in 36% of the cases and high grade histological criteria were found in 22% of the dysplasias. Oncogenic HPVs were detected more frequently in HIV infected patients (35% v 12%) and more than one HPV type was found in 21.5% of cases. Neither the anogenital diffusion of the HPV lesions nor their morphological, histological, and virological features differed significantly in patient with CD4 cell counts > or < 200 x 10(6)/l. In contrast, patients with CD4 cell counts < 50 x 10(6)/l had a higher risk of several types of HPVs and of developing a diffuse anogenital infection. CONCLUSION: HIV-1 infected patients had an increased frequency of high grade anogenital dysplastic lesions and a higher frequency of HPV infection with multiple and diffuse sites of involvement. These characteristics of HPV infection were independent of the patients' immune status up to CD4 cell counts > 50 x 10(6)/l but showed an increased risk when the CD4 cell count was < 50 x 10(6)/l. The higher frequency of diffuse anogenital infections among HIV infected men calls for rapid treatment, laser or surgery, given the association of histological features of intraepithelial neoplasia and the presence of multiple HPV infection sites which may be the consequence of immune disturbances, most of which are transmissible potentially oncogenic HPVs.     

Occurrence of human papillomavirus infection in cervical intraepithelial neoplasia. A retrospective histopathological study of 317 cases treated by laser conization

The aim of the study was to compare the histological outcome of the cone specimens with the diagnoses of the preoperative biopsies, to assess the distribution of histological features consistent with human papillomavirus (HPV) infection and, finally, to analyse the impact of cellular HPV features on classification of cervical intraepithelial neoplasia (CIN). The study comprised a population of 317 women treated for CIN by laser conization during the period 1983-85. A total of 634 cervical specimens (317 preoperative biopsies and their corresponding cones) were studied retrospectively for CIN classification and examined for morphological signs of HPV infection. For presentation of the results, we used a modified terminology for CIN. Low-grade (LG) CIN included borderline lesions and CIN I, while high-grade (HG) CIN included CIN II and CIN III. The blinded histopathological review revealed HG CIN both in the preoperative biopsies and the cones in 71% of the cases. LG CIN or benign lesions were found in the preoperative biopsies and their corresponding cone specimens in 6% of the study population. HPV features were present in 65% of the preoperative biopsies, and were most prevalent in women under 29 years of age (p < 0.001). Thirteen percent of the total biopsy material was downgraded. The downgrading was most prevalent among original CIN II (p = 0.009) and HPV-negative biopsies (p < 0.001). This study demonstrates that CIN lesions are frequently associated with HPV features, which are significantly more prevalent in the youngest women. Concomitant HPV features do not influence the CIN classification.     

Prevalence of human papillomavirus infection and HPV DNA among male partners of Israeli women with genital premalignant and human papillomavirus lesions

The role of the males who are sexual partners of females with genital human papillomavirus (HPV) infection and premalignant lesions is explored in the present study. Within a period of 3 years, 391 females with genital premalignant and HPV-associated lesions were examined and treated at the Cervical Pathology Unit of the Tel Aviv Medical Center. The male partners of all the women were asked to attend this unit, and 322 of them responded. All participants underwent colposcopic examination of the anogenital area followed by colposcopically guided biopsies from the most representative lesions, when present, part of which included in situ hybridization (ISH) of HPV DNA sequences 6/11 and 16/18. The histological prevalence of HPV among the male partners was 86.6% (185 of 213 biopsies). Of the 48 couples who had ISH evaluations, the ISH could not identify any copy of HPV DNA in 58.3% of the males (28 cases) and 41.6% of the females (20 cases). Among the males, HPV 6/11 and 16/18 were found in 17 (35.4%) and 3 cases (6.2%), respectively, and among the females there were 23 (48.0%) and 5 cases (10.4%), respectively. Correlation of HPV DNA sequences 6/11 and 16/18 between the couples was found in six (12.5%) and in one (2.0%), respectively. These data do not support a direct contamination by the current male partner. The question of treating the male partner of a woman with genital HPV and premalignant lesions remains to be evaluated.     

Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.     

Chlamydia infection and CIN

Under the hypothesis that a chronic infection of the cervical epithelium leads to a reduction in the immunological response, a study was carried out to compare the possible relationship between chlamydial infection and CIN. 187 patients were referred to hospital for histological confirmation because of a cytological smear result (PAP III and IV a). Smears were examined for chlamydia antigens using immunofluorescence. The presence of antichlamydial IgA and IgG was performed in serum using an indirect immunohistochemical method. These tests confirmed CIN in 163 patients. The infection rate with chlamydia was 52.9%, 15.9% of CIN patients showing an active chlamydial infection. Inclusion of topographical findings, together with differential evaluation of colposcopic results, with reference to the transformation zone, allow for a separation between inflammation and dysplasia. The confirmation of a positive chlamydial infection and colposcopic criteria may help to reduce the high percentage of false-positive findings in the problem-group of PAP III patients. It appears that reservations about smear controls after doxycyclin therapy--including treatment of sexual partners--is justified.     

Rare association of human herpesvirus 6 DNA with human papillomavirus DNA in cervical smears of women with normal and abnormal cytologies

We investigated by nested PCR the possible association of human herpesvirus 6 (HHV-6) and human papillomavirus (HPV) genomes in the cervixes of 109 women with normal and abnormal cytological smears. HPV DNA was detected in 8.33% of 24 women with normal cytologies and in 41.1% of 85 women with abnormal cytologies; the proportion of HPV DNA was directly related to the severity of the lesions. HHV-6 DNA was found in only one patient, who had a cytological pattern of koilocytosis. The HHV-6 genome was classified by restriction enzyme analysis as variant B. The study indicates that detection of the HHV-6 genome in the cervixes of women with a wide spectrum of gynecological complaints is a rare event and rules out the possible association between HHV-6 and HPV genomes in cervical cancer lesions.     

Screening for cervical cancer: experience from the Colposcopy Clinic at Harare Hospital

A study was carried out to determine the prevalence of cervical intra-epithelial neoplasia (CIN) among women referred to Harare Hospital Colposcopy Clinic with a history of an abnormal smear. During the period, 132 patients were seen and 79 (60 pc) had colposcopic findings suggestive of CIN and 17 (13 pc) had inflammatory changes and 36 (27 pc) had normal findings. Electrocautery was used to treat low grade CIN lesions, cone biopsy was performed for higher grades of CIN and a selected group underwent hysterectomy.     

Cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection

Many studies have shown a strong correlation between CIN and HPV infection. Molecular biology has allowed identification of types of HPV which seem to be connected, more frequently than others, to dysplastic lesions. Physical state of HPV-genome seems to play an important role in the development of cervical cancer. In this study the HPV-genome has been searched in tissue specimens obtained from 34 women affected by CIN II and III. All patients underwent laser conization. Immediately before treatment, colposcopically directed biopsies of the cervical lesion and of the areas with no colposcopically apparent disease were taken and on these samples, HPV-DNA has been searched, isolated and analysed for HPV types and physical state. Histologic examination on cones showed 6 cases of CIN II (3 with HPV), 24 cases of CIN III (14 with HPV), 1 microinvasive carcinoma and 3 with no residual lesion. Southern blot analysis detected HPV-DNA in 4 cases of CIN II (16.7%) and in 20 cases of CIN III (70.6%). In 50% of CIN II and 85% of CIN III HPV 16 DNA has been found and in the remaining 50% of CIN II and 15% of CIN III HPV 31 DNA has been detected. All CIN II and 14 cases of CIN III showed episomal HPV-DNA. Integrated HPV-DNA has been found in 3 cases of CIN III and the other 3 cases of CIN III showed both integrated and episomal HPV-genome. Integrated form has been noticed only for HPV 16 type. In no case of colposcopically normal tissue has HPV-DNA been found. These data seem to confirm the strong correlation between HPV 16 type, which often has integrated form, and CIN III strengthening the hypothesis of its potential oncogenic action.     

Emerging and re-emerging infectious diseases: a biological evolutionary drama

Cervical intraepithelial neoplasia grade 3 (CIN 3) is treated surgically. Follow-up of these patients is important to ensure successful treatment. The present study was undertaken to determine whether human papillomavirus (HPV) testing can be used to discriminate patients who will have recurrences from those who will not. It is composed of 26 patients who presented with recurrences of CIN and 22 patients who remained disease-free after treatment. DNA was extracted from paraffin-embedded cone biopsies of incident CIN 3, their corresponding follow-up Pap smears taken 3 months postoperatively, and their secondary cone biopsies of the recurrent lesions. The extracted DNA were then analyzed by PCR for the presence of HPV. The posttreatment cervical smears in the recurrent group had a (25/26) 96% HPV prevalence, while HPV DNA was not detectable in any of the 22 patients in the control group. The HPV types in both the initial and recurrent lesions correlated very well. This suggest that most recurrences are likely to be due to persisting lesions or subclinical HPV infections that had not been completely removed. Cytology alone was not sufficiently sensitive to discriminate the patients at risk for recurrences. It appears that HPV testing can be useful to monitor the therapeutic result.     

Metals pollution in marine sediments of the United Arab Emirates creeks along the Arabian Gulf shoreline

In order to evaluate the association between seropositivity for herpes simplex virus (type 1 and type 2) and cervical intraepithelial neoplacia (CIN), we analysed data from a population-based case-control study of CIN grade II-III which included Norwegian women aged 20 to 44 years, 94 cases and 228 controls. Our objectives were to determine if HSV-1 and/or HSV-2 seropositivity were independent risk factors for CIN, taking human papillomavirus exposure into account, and to elucidate the combined effect of HPV positivity and seropositivity for HSV In logistic regression analyses, the association between HSV-2 or HSV-1 seropositivity and CIN II-III was not explained by HPV (adjusted OR 3.0; 95%, CI 1.3-7.2 and adjusted OR 3.3; 95% CI 1.3-8.4, respectively). In analyses restricted to HPV-16 DNA-positive individuals, seropositivity for HSV-2 increased the risk of CIN (OR 11.1; 95% CI 1.2-105.7), whereas HSV-1 seropositivity was not significantly associated with CIN. In women positive for other HPV types, only HSV-1 seropositivity was associated with CIN (OR 8.5; 95% CI 1.3-55.8). In analyses of the HPV-16-seropositive individuals, neither HSV-1 nor HSV-2 seropositivity was associated with CIN. Compared to the reference group of jointly unexposed subjects, the HPV-16 DNA-positive women who were anti-HSV-2 negative had an increased risk of CIN (OR 29; 95% CI 12-67), whereas the risk in women who were both HPV-16 DNA-positive and HSV-2 was OR=247 (95% CI 31-1996). The estimate of interaction was strong, but did not reach significance, and our findings may suggest that the combined effect of the two viruses is of aetiological importance in cervical carcinogenesis. Furthermore, the results indicate that HPV DNA positivity is not sufficient to explain the sexual behaviour-associated risk of cervical neoplasia and that further studies on the role of genital HSV (type 1 as well as type 2) and other STDs are warranted.