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The natural history of human papillomavirus (HPV) atypia of the cervix.

This study examines the natural history of human papilloma virus (HPV) atypia of the cervix in 259 untreated patients who were followed for 3 to 74 months (median 18 months). Progression to cervical intraepithelial neoplasia (CIN) occurred in 41 patients (15.8%)--all but 3 progressions occurred within the first 24 months of follow-up. In no patient did invasive cancer develop during this study. Persistence occurred in 39.4% and regression in 44.8% patients. An increasing number of regressions were noted with the passage of time. Progression to histologically confirmed CIN which occurred in 23 of 46 (50%) patients in whom both the cytological and colposcopic assessment at the first visit suggested CIN did so significantly more frequently than when either the cytology or colposcopy alone suggested CIN (11 progressions in 83 patients--13.3%, p less than .00001) or when neither cytology nor colposcopy suggested CIN (7 progressions in 119 patients--5.9%, p less than .000001). We recommend that patients with both cytological and colposcopic features suggestive of CIN should be treated even though HPV atypia only is reported on biopsy. Those who are not treated should be followed closely until regression occurs and consideration should be given to treating those patients in whom the abnormality persists longer than 2 years.

Adult↗

Mild cervical atypia: a management dilemma.

This study examined 117 patients with mild cervical atypia or atypical squamous cells of uncertain significance; it was found that 25% had histologically proven CIN lesions by colposcopically-directed punch biopsy or cone biopsy. 18% were found to have at least CIN 2 lesions and there was 1 case of invasive cancer. These data strongly support the recommendation of early colposcopic referral in patients with mild cervical atypia.

Adolescent↗

Prostitution and other cofactors in preinvasive and invasive lesions of the cervix.

OBJECTIVE: To examine risk factors for preinvasive and invasive lesions of the cervix in Venezuelan female sex workers (FSW). METHODS: A total of 438 FSW were analysed. Each FSW had their clinical history recorded, a gynaecological examination, a Pap smear and a colposcopic examination of the cervix. A cervical biopsy was taken under colposcopic guidance when there was an abnormal epithelium. The statistical methods used were Student's t-test, chi(2) test and logistic regression. RESULTS: The sex workers' mean age was 32.1 +/- 7.9 years old (mean +/- standard deviation). The age of the first sexual intercourse activity for the FSW was 15.9 +/- 2.1 years. Sixty-four of the 84 women (76.2%) who had cervical biopsies had preinvasive and invasive lesions; 41 (9.4%) had cervical intra-epithelial neoplasia (CIN) 1, 12 (2.7%) had CIN 2, eight (1.8%) had CIN 3, two (0.5%) had microinvasive carcinoma, and one (0.2%) had invasive carcinoma. Forty of these 64 women (62.5%) with preinvasive or invasive lesions had a concurrent histological diagnosis of human papilloma virus (HPV) infection (P < 0.0001). The FSW with cervical pathology were younger (P < 0.05) and had their first sexual intercourse earlier (P < 0.02) than FSW with no pathology. Two hundred and seventy-six (63%) of the FSW were current smokers, and 47 of these women (17.6%) had cervical pathology (P < 0.03). CONCLUSIONS: First sexual experience before 20 years of age, cigarette smoking and HPV infection were high-risk factors for preinvasive and invasive lesions of the cervix in Venezuelan FSW.

Adolescent↗

Role of human papillomavirus DNA testing in management of women with atypical squamous cells of undetermined significance.

To find the sensitivity, specificity, and positive and negative predictive values of the high-risk group human papillomavirus (HPV) DNA testing as a triage tool to detect high-grade squamous intraepithelial lesions (HSILs, ie, cervical intraepithelial neoplasia [CIN] 2 or worse) in women with a cytologic smear showing atypical squamous cells of undetermined significance (ASC-US). All new cases with cytologic smears showing ASC-US that presented in King Chulalongkorn Memorial Hospital from January 2003 to November 2003, excluding known cases of HSILs and pregnancies, were enrolled. Cervical cell samplings were done by cervical cytobrush technique and tested for high-risk group HPV with the Hybrid Capture 2 (HC2) test. All participants were examined under a colposcope. Then cervicographs were taken before colposcopic-directed cervical biopsies were done. Of the 90 ASC-US cases enrolled, the pathologic results were normal in 30.0%, squamous metaplasia in 16.7%, CIN 1 in 37.8%, CIN 2 in 1.1%, CIN 3 in 11.1%, and microinvasive cervical carcinoma in 3.3%. The prevalence of HSILs and the prevalence of high-risk HPV detection were 15.6% and 38.9%, respectively. Using pathologic results from cervical biopsy as the gold standard, the HC2 has the sensitivity, specificity, and positive and negative predictive values of 85.7%, 69.7%, 34.3%, and 96.4%, respectively, to detect HSILs. High-risk group HPV detection can be used as an additional triage test to detect HSILs in women having ASC-US with high sensitivity and negative predictive value.

Adolescent↗

Analyses of atypical squamous cells refined by the 2001 Bethesda System: the distribution and clinical significance of follow-up management.

This study was conducted to analyze the clinical significance of follow-up diagnostic methods of atypical squamous cells (ASC) (the 2001 Bethesda System) cases according to age. A computerized search of the cytology database was performed to retrieve all cases diagnosed as ASC from 2001 to 2003. The pathologic reports for all follow-up diagnoses were reviewed. We divided the patients into two groups according to their age, younger than 50 years of age and 50 years and older, and follow-up diagnoses were compared between the two groups. ASC was identified in 1035 (2.0%) of 49,882 women screened, and a total of 914 patients were eligible. In atypical squamous cells of undetermined significance (ASC-US) cases, colposcopically directed biopsy showed CIN I (CIN is cervical intraepithelial neoplasia) or higher grade lesions in 34.9% of cases younger than 50 years of age and in 17.4% of cases 50 years and older (P= 0.000). However, repeat Pap smears and human papillomavirus DNA testing showed no differences between the two groups. In contrast, the three methods did not exhibit significant difference between the two groups in patients with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) (P= 0.743). Colposcopically directed biopsy for the ASC-US was more useful in patients younger than 50 years of age than in those who were 50 years and older. It is suggested that age should be considered in deciding follow-up diagnostic methods in patients with ASC-US.

Adult↗

Women in a region with high incidence of cervical cancer warrant immediate colposcopy for low-grade squamous intraepithelial lesion on cervical cytology.

The objective of this study was to determine the prevalence of high-grade histologic diagnoses in women who had low-grade squamous intraepithelial lesion (LSIL) on Pap smear in an area with high incidence of cervical cancer. We conducted a retrospective study of 220 women with LSIL cytology undergoing colposcopic examination in Chiang Mai University Hospital between January 1999 and July 2004. The histologic diagnoses, obtained from colposcopically directed biopsy or electrical loop excision after initial colposcopy, showed that 80 (36.4%) women had histologically confirmed high-grade lesions and 11 (5%) women had microinvasive (9) and frankly invasive (2) carcinomas. Overall, 41.5% of women with LSIL on Pap smear had significant underlying lesions, requiring appropriate treatment. In conclusion, in the region with high incidence of cervical cancer, women with LSIL cytology are at increased risk of having underlying high-grade lesions and invasive cancer. Immediate referral for colposcopy is warranted.

Adolescent↗

Psychologic morbidities prior to loop electrosurgical excision procedure in the treatment of cervical intraepithelial neoplasia.

The objective of this study was to assess and compare anxiety and distress in patients undergoing colposcopic examinations and loop electrosurgical excision procedure (LEEP). Patients seen for evaluation of cervical intraepithelial neoplasia (CIN) and LEEP were recruited. All patients received further teaching with respect to their abnormality right after the colposcopic evaluation by nursing staff. The Hospital anxiety and Depression Scale (HADS) and the Psychosocial Effects of Abnormal Pap Smears (PEAPS) questionnaires were used to measure and compare distress between the two groups. Linear regression models were built to identify significant predictive variables for psychologic morbidities. Twenty-one colposcopy and 20 LEEP patients participated in this study. No significant demographic differences were noted. Eighty-one percent of patients having colposcopy and 65% of those undergoing LEEP can be classified as having significant anxiety and depression based on the HADS questionnaire. Patients undergoing LEEP scored significantly better than colposcopy patients on the mean total PEAPS score and on the self-belief/cancer concern and effects on sexual relationship dimension scores. Significant psychologic morbidities exist in patients diagnosed with CIN. Face-to-face individualized education and support after colposcopy can decrease patients' distress at subsequent treatment visits.

Adult↗

The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia.

The objective of this study was to assess the performance of cervical impedance spectroscopy in the detection of cervical intraepithelial neoplasia (CIN) using the new MKIII impedance probe. A prospective observational study recruited women referred to colposcopy with an abnormal Papanicolaou smear. A pencil probe incorporating four gold electrodes was used to measure electrical impedance spectra from cervical epithelium. Colposcopy examinations, including probe positioning, were video recorded to allow for correlation between results obtained from colposcopic impression, histopathologic examination of colposcopic punch biopsies, and impedance measurements. Cervical impedance-derived parameters R, S, R/S, C, and Fc were assessed to see if significant difference in values obtained in CIN and normal epithelium existed. The performance of the probe in identifying women with CIN was also assessed. One hundred seventy-six women were recruited and 1168 points analyzed. Parameters R, S, and Fc showed significant separation of CIN or squamous intraepithelial lesion (SIL) from squamous, mature metaplastic, and columnar epithelium. Sensitivities of 74% and specificity of 53% can be achieved in identifying CIN 2/3 (High-grade SIL) in screened women. We conclude that cervical impedance spectrometry provides a potentially promising real-time screening tool for CIN with similar sensitivity and specificity to currently used screening tests. Further research is ongoing to develop the probe for potential clinical use.

Cervix Uteri↗

Symptoms of chronic vaginal infection and microscopic condyloma in women.

The purpose of this study was to determine if women who self-reported symptoms of chronic vaginal infection might be at risk for microscopic condyloma and, therefore, in need of colposcopic examinations. The hypothesis tested was that women who report yeast-type symptom chronicity and who have yeast-negative laboratory studies will have a significant incidence of microscopic vulvar condyloma. The hypothesis was supported by the results. Findings show a need to broaden the use of the colposcope to detect condyloma in women with a chronicity of unexplained yeast-type symptoms.

Adolescent↗

Localization and staging of cervical intraepithelial neoplasia using double ratio fluorescence imaging.

A phase zero evaluation of a new fluorescence imaging technique for diagnosing cervical intraepithelial neoplasia (CIN) was performed. The fluorescence imaging prototype performed quantitative imaging of Protoporphyrin induced by a topically applied aminolevulinic acid using double ratio (DR) fluorescence imaging technique developed by our group. A total of 38 patients were in the protocol, with 16 colposcopically selected for biopsy. Fluorescence images of these 16 patients were taken, 19 sites were biopsied, and the disease was staged histopathologically. DR fluorescence imaging of the cervix using our general purpose prototype appeared to be cumbersome but feasible. In four cases strongly localized fluorescent hotspots were observed at the location where the disease was colposcopically visible. In the other cases the fluorescence showed a more diffuse multifocal image. The value of the DR determined at the site of biopsy correlated in a statistically significant way with the histopathologically determined stage of the disease [Spearman rank correlation, r=0.881, p<0.001 (confidence interval 0.7044-0.9552)]. This suggests that noninvasive staging of CIN using this technique is feasible. We believe that the results of this study justify the development of a dedicated device that combines regular white light colposcopy with DR fluorescence imaging.

Adult↗

Human papillomavirus infection and cervical intraepithelial neoplasia in women with renal allografts.

An increased prevalence of cervical cancer has been observed in immunosuppressed women, but controlled studies are rare. Biopsy specimens from 49 women with renal allografts and 69 non-immunosuppressed controls (with no history of cervical intraepithelial neoplasia, vulval warts, or abnormal results of cervical smear tests) were assessed for colposcopic appearance, cytological and histological diagnosis, and the presence of human papillomavirus types 6/11 and 16/18 DNA sequences. At colposcopy 26 (53%) of the women with allografts had cervical abnormalities compared with 20 (29%) of the controls. The prevalence of cervical intraepithelial neoplasia was significantly higher in the women with allografts (24 (49%) compared with 7 (10%]. The overall rate of detection of human papillomavirus DNA did not differ significantly between the two groups. There was however, a significant difference in the rate of detection of human papillomavirus type 16/18 DNA (27% in the women with allografts and 6% in the controls). These data confirm that pathological and virological changes affecting the cervix are significantly increased in immunosuppressed women and emphasise the need for regular colposcopic examination.

Adult↗

Colposcopy services in the West Midlands region.

A survey of all 72 consultant gynaecologists in the West Midlands region was carried out to determine their views on colposcopy services. All districts provided a colposcopy service and 47 consultants practised colposcopy. The consultants differed considerably in their views on criteria for referring women for investigation after smears. All but one thought that a positive smear result was an indication for immediate referral but whereas 55 thought that women with one or more inflammatory smear should be referred, 17 did not believe this to be necessary. Sixty seven consultants thought a preoperative colposcopic assessment desirable, but 10 had to ration referrals because of limited resources. Four forms of treatment were used: 17 districts had a carbon dioxide laser, eight used low voltage diathermy loop excision, two had only a cold coagulator, and one used only cold cautery. There was widespread dissatisfaction with resources and about the increasing amount of time spent on the service at the expense of other work. Consultants were also concerned about the relevance of much of what was done to the aim of the screening programme--reducing mortality from cervical cancer. Although additional resources are needed in some districts, referral policies, indications for colposcopic assessment, training, choice of treatment, and the value of follow up need to be reviewed if the service is to be improved.

Adult↗

Implications of inflammatory changes on cervical cytology.

OBJECTIVE: To assess premenopausal women with inflammatory changes on cervical cytology for genital infections and cervical abnormalities. DESIGN: Prospective study of women attending general practice and family planning clinics who had a recent cervical cytology result with inflammatory changes. SETTING: Department of genitourinary medicine. PATIENTS: 102 Premenopausal women with recent cytology result showing inflammatory changes and with no history of antibiotic or antifungal treatment since their smear. INVESTIGATIONS: Genital examination and microbiological screening for genital infections; colposcopic examination about six weeks later. MAIN OUTCOME MEASURES: Detection of genital infections, particularly those sexually acquired, and abnormalities on colposcopy. RESULTS: Genital infections were isolated in 77 patients, and one or more sexually acquired infections were found in 22. Prevalence of sexually acquired infections was significantly correlated with younger age (particularly being under 25), being single, separated, or divorced; using non-barrier contraception; and recent change of sexual partner. An abnormality on colposcopy was found in 36 women. There was a strong correlation of a sexually acquired infection with an abnormality at colposcopy; hence younger women were more likely to have a colposcopic abnormality. CONCLUSIONS: Inflammatory changes on cytology are often associated with the presence of a sexually acquired infection and premalignant disease of the cervix, particularly in younger, single women using non-barrier contraception.

Adolescent↗

How many histological levels should be examined from tissue blocks originating in cone biopsy and large loop excision of the transformation zone specimens of cervix?

AIMS: To establish the value of examining additional histological levels in cone biopsy and large loop excision of the transformation zone (LLETZ) specimens of cervix. METHODS: Three deeper levels were examined from 200 consecutive cone biopsy and LLETZ specimens reported by a single pathologist. RESULTS: Examination of the first deeper level resulted in cervical intraepithelial neoplasia (CIN) being identified for the first time in five cases and in CIN1 being upgraded in five more. Invasive cancer was discovered in two cases that had shown high grade CIN initially. CONCLUSION: Examination of a single further level appears to be sufficient in those patients in whom a specimen is compromised because epithelium including the squamocolumnar junction is missing, or if there is a discrepancy between the histological findings and the preceding colposcopic or cytological history. If invasive disease is suspected on the basis of the cytological, colposcopic, or histological features, one or preferably two further levels should be examined.

Biopsy↗

The Italian experience of a Pap test and speculoscopy based screening programme.

OBJECTIVES: The main objective of the study was to evaluate if speculoscopy, a magnified chemiluminescent examination, combined with a Pap smear, could improve the detection of early cervical lesions compared with the Pap smear alone. SETTING: Pap tests and speculoscopies were performed in two family planning centres located in the surrounding areas of Modena. Colposcopic investigations and biopsies of the uterine cervix were performed in a second level centre (Gynaecological Prevention Centre of Modena Policlinico). Histological specimens were analysed at the Section of Pathological Anatomy of Modena Policlinico. SUBJECTS: The study population comprised 1000 women aged 25-64 years, invited to undergo a Pap smear every three years in accordance with the screening programme for cervical cancer started in Modena in 1997. METHODS: Midwives performed the Pap smear and speculoscopy in succession. Women with a positive Pap test and/or positive speculoscopy underwent colposcopy and, if colposcopic findings were positive, targeted punch biopsies were performed. RESULTS: A total of 1000 patients were subjected to cytology and speculoscopy examinations. Among these women, 10 had abnormal Pap smear findings whereas 144 had an abnormal speculoscopic pattern. Only three of 59 patients with a histological diagnosis of cervical intraepithelial neoplasia grade I (CIN I)/human papillomavirus and only three of seven patients with CIN II/CIN III had a positive Pap test. CONCLUSIONS: Speculoscopy combined with a Pap test can significantly increase the detection of cervical lesions when included in a screening programme.

Adult↗

Screening for cervical intraepithelial neoplasia and cancer in the Sheffield STD clinic.

I undertook a prospective study of the incidence of histologically confirmed cervical intraepithelial neoplasia (CIN) and cancer in women attending a sexually transmitted disease (STD) clinic, and correlated the findings to cervical cytology reports, age, and history of STD of the affected women. Of 2017 women screened, 75 (3.7%) had dyskaryotic cervical smears. Colposcopically directed biopsy tests gave an overall detection rate of 0.55% for CIN3, which was similar to the national average. The false negative rate was 2.9% and cytology tests alone underestimated the degree of pathological change in 12 (30%) of 40 women with mild dyskaryosis. Women under 20 years old made up 43% of those with CIN1 and 38% of those with CIN2. The detection rate of CIN3 was 0.65% for women aged 15-34, which was higher than the national average and suggested earlier onset of CIN3 in our clinic population. There was a high association between genital warts and cervical precancer. This preliminary study confirms the need for routine non-selective screening of women attending STD clinics by cervical cytology tests, colposcopic examination, and biopsy tests where indicated.

Adolescent↗

Anal human papillomavirus infection: a comparative study of cytology, colposcopy and DNA hybridisation as methods of detection.

OBJECTIVE: To compare anal cytology, colposcopy and DNA hybridisation as methods of detecting anal HPV infection. SUBJECTS AND DESIGN: Patients attending: (1) a genitourinary medicine (GUM) clinic with ano-genital warts; (2) a surgical out-patient department with anal fissure or haemorrhoids were examined for evidence of anal HPV infection. RESULTS: Considering GUM clinic attenders, 17% (38/225) and 40% (90/225) had perianal or anal canal warts respectively. Colposcopic examination revealed anal acetowhite lesions without warts in 28% (63/225). Cytological evidence of HPV infection was found in 98%, 83%, and 90% of patients with anal canal warts, perianal warts and acetowhite lesions respectively. Anal intraepithelial neoplasia (AIN) was documented in 22% of patients with anal canal warts compared with 6% with perianal warts (p less than 0.01). HPV DNA was detected from the anal brushings of 71%, 50%, 32%, and 29% of patients with anal canal warts, perianal warts, acetowhite lesions and a normal anal examination respectively. HPV type 6/11 was detected in the majority of HPV positive samples. Considering surgical out-patient attenders with no history or signs of anal warts, 25% showed cytological evidence of anal HPV infection and HPV DNA was detected from anal brushings in 3% (2/71). CONCLUSION: Anal examination with the colposcope is a useful method for detecting subclinical HPV infection. Anal cytology may prove helpful for detecting AIN, however, since koilocytosis was rarely seen, the specificity of the cytological criteria for anal HPV infection in the absence of AIN is uncertain. DNA analysis of anal brushings proved only moderately sensitive.

Adult↗

Assessment of psychiatric morbidity in patients attending a colposcopy clinic situated in a genitourinary medicine clinic.

OBJECTIVE: To determine the adverse psychological implications of referral for colposcopic screening within a genitourinary medicine clinic. DESIGN: Cross sectional survey. SETTING: A colposcopy clinic held within a genitourinary medicine clinic. SUBJECTS: 160 consecutive women referred to the clinic were assessed for psychiatric morbidity using the General Health Questionnaire (GHQ-28). Women were referred to the colposcopy clinic because of one or more of the following: abnormal cervical cytology, condylomata acuminata, HIV antibody positivity. A history of prior local ablative therapy to the cervix was also included in the analysis. RESULTS: There was no difference in psychiatric morbidity, as detected by the GHQ-28, in women referred to the clinic because of abnormal cervical cytology or condylomata acuminata. The total GHQ-28 scores indicated a significant increase in psychiatric morbidity, with increased sub-scores indicating social dysfunction, anxiety and somatic symptoms, in women who had had prior laser therapy to the cervix. Women with HIV infection attending the clinic were noted to have an increase in GHQ-28 sub-scores indicating social dysfunction and depression. CONCLUSIONS: Women who have undergone laser therapy to the cervix may benefit from psychological evaluation and supportive measures if they develop further genital lesions which require colposcopic evaluation. Women with HIV infection need further psychological evaluation prior to planning intervention and preventative strategies.

Anxiety Disorders↗