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Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma.

ABSTRACT: Diagnosis and treatment of cervical cancer precursors rely on colposcopic biopsy, which is sometimes hampered by incorrect biopsy placement and the unclear prognostic value of poorly reproducible diagnoses such as cervical intraepithelial neoplasia (CIN) Grade 1 and 2. Searching for discrete disease categories that incorporate the value of cytology and that reflect the causal role of particular HPV types, we analyzed histology, cytology and HPV genotype distributions in the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED). This cross-sectional study comprises approximately 1,700 women referred to colposcopy or treatment for the spectrum of cervical disease, including 439 women with

SUBMITTER: Wentzensen N

PROVIDER: S-EPMC2796188 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma.

Wentzensen Nicolas N Schiffman Mark M Dunn S Terence ST Zuna Rosemary E RE Walker Joan J Allen Richard A RA Zhang Roy R Sherman Mark E ME Wacholder Sholom S Jeronimo Jose J Gold Michael A MA Wang Sophia S SS

International journal of cancer 20090201 4

Diagnosis and treatment of cervical cancer precursors rely on colposcopic biopsy, which is sometimes hampered by incorrect biopsy placement and the unclear prognostic value of poorly reproducible diagnoses such as cervical intraepithelial neoplasia (CIN) Grade 1 and 2. Searching for discrete disease categories that incorporate the value of cytology and that reflect the causal role of particular HPV types, we analyzed histology, cytology and HPV genotype distributions in the Study to Understand C ...[more]

PMID: 19030188

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Project description:INTRODUCTION: Despite the availability of preventive strategies (screening tests and vaccines), cervical cancer continues to impose a significant health burden in low- and medium-resourced countries. HIV-infected women are at increased risk for infection with human papillomavirus (HPV) and thus development of cervical squamous intraepithelial neoplasia (CIN). METHODS: Study participants included HIV-infected women enrolling the prospective open cohort of Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation (IPEC/FIOCRUZ). At cohort entry, women were subjected to conventional Papanicolaou test, HPV-DNA test and colposcopy; lesions suspicious for CIN were biopsied. Histopathology report was based on directed biopsy or on specimens obtained by excision of the transformation zone or cervical conization. Poisson regression modeling was used to assess factors associated with CIN2+ diagnosis. RESULTS: The median age of the 366 HIV-infected women included in the study was 34 years (interquartile range: 28-41 years). The prevalence of CIN1, CIN2 and CIN3 were 20.0%, 3.5%, and 2.2%, respectively. One woman was found to have cervical cancer. The prevalence of CIN2+ was 6.0%. Factors associated with CIN2+ diagnosis in the multivariate model were age < years compared to ≥ 35 years (aPR = 3.22 95%CI 1.23-8.39), current tobacco use (aPR = 3.69 95%CI 1.54-8.78), nadir CD4 T-cell count <350 cells/mm3 when compared to ≥ 350 cells/mm3 (aPR = 6.03 95%CI 1.50-24.3) and concomitant diagnosis of vulvar and/or vaginal intraepithelial lesion (aPR = 2.68 95%CI 0.99-7.24). DISCUSSION: Increased survival through wide-spread use of highly active antiretroviral therapy might allow for the development of cervical cancer. In Brazil, limited cytology screening and gynecological care adds further complexity to the HIV-HPV co-infection problem. Integrated HIV care and cervical cancer prevention programs are needed for the prevention of cervical cancer mortality in this group of women.

Project description:BackgroundThe distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer.MethodsHIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint.ResultsCIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and 'carcinogenic' HPV genotypes were present in 35.3% (98/278) HIV-infected women. 'Possibly carcinogenic' and 'non/unknown carcinogenic' HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (? 2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple 'carcinogenic' HPV genotypes were present in just over a quarter (27.8%) of women with 'carcinogenic' HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with 'carcinogenic' HPV type detection were reporting ? 2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy.ConclusionHPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.

Project description:ObjectivesTo increase effectiveness of the cervical cancer screening program, self-sampling can be an option. Both self-collected vaginal samples (SCV) and urine samples may be useful alternatives to clinician-taken cervical samples (CS).DesignCross-sectional study.SettingColposcopy clinic.ParticipantsWomen (n=305) referred to colposcopy after abnormal cervical screening result or conditions like postcoital bleeding.InterventionAll women self-collected a urine and a vaginal sample prior to colposcopy, where a CS and biopsies were taken. All samples were tested for high-risk human papillomavirus (HPV) using the Cobas HPV assay. The gold standard was histology diagnoses (CIN2+/CIN3+) from biopsies obtained at the same examination.Primary outcomeAbsolute and relative sensitivity and specificity of HPV testing on SCV and urine to detect CIN2+/CIN3+ compared with the CS.Secondary outcomeThe acceptability by women of self-sampling.ResultsBoth the vaginal and urine sample were comparable to the CS in identifying severe intraepithelial neoplasia (CIN2+/CIN3+). Absolute sensitivity ranged from 93% for urine samples to 96% for SCV for detecting CIN2+, which is comparable to the sensitivity of CS (overlapping 95% CI).The relative sensitivity for detecting CIN2+ was 1.00 (95% CI 0.96 to 1.04) for SCV and 0.96 (95% CI 0.91 to 1.03) for urine samples. At CIN3+, the relative sensitivity was 1.00 (95% CI 0.96 to 1.08) and 0.97 (95% CI 0.89 to 1.07) for SCV and urine samples, respectively. There were no statistical differences between the self-collected samples and the CS (McNemar's test >0.05). The relative specificity was also similar (1.03 (95% CI 0.95 to 1.12) for SCV and 0.98 (95% CI 0.89 to 1.09) for urine samples) (McNemar's test >0.05).The acceptability of self-sampling was evaluated by questionnaire. The women found the instructions on sample collection easy to understand and were positive about self-sampling with a preference for the urine sample.ConclusionSelf-sampling by SCV and urine is a clinically safe alternative to CS with a high degree of acceptability.

Dataset Information

Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma.

Publications

Grading the severity of cervical neoplasia based on combined histopathology, cytopathology, and HPV genotype distribution among 1,700 women referred to colposcopy in Oklahoma.

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