Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions.

BACKGROUND: Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. METHODS: In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. RESULTS: High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to 86.2%, and the specificity from 53.5% to 69.7%. For the samples collected by physicians, the sensitivity was 98.3% and the specificity 52.1%. The self-sampling methods were generally acceptable to the women: 98.4% of respondents (126/128) deemed urine sampling acceptable, 92.9% (118/127) found vulvar sampling acceptable, and 88.2% (112/127) found vaginal sampling acceptable. INTERPRETATION: Self-collection of samples for HPV testing was acceptable to women attending a colposcopy clinic for investigation of suspected cervical lesions and shows sufficient sensitivity to warrant further evaluation as a screening test for cervical cancer prevention programs.

HPV testing in primary screening of older women.

Certain types of the human papilloma virus (HPV) are well established as the primary cause of cervical cancer. Several studies have shown that HPV testing can improve the detection rate of high-grade cervical intraepithelial neoplasia (CIN), but these have been carried out primarily in younger women. In this study we evaluated the role of HPV testing as an adjunct to cytology in women aged 35 or over. An additional aim was to evaluate commercially available kits for HPV testing. A total of 2988 eligible women aged 34 or more attending for a routine smear in 40 general practitioner practices received HPV testing in addition to routine cytology, after having given written informed consent. Samples were assayed by polymerase chain reaction (PCR) and two versions of the Hybrid Capture test for HPV, and women were invited for colposcopy if there was any cytological abnormality (including borderline smears) or the PCR test was positive. Any apparent abnormality was biopsied and loop-excision was performed as necessary. CIN was judged by histology; 42 women had high-grade CIN, of which six were cytology negative (86% sensitivity for borderline or worse) and three had a borderline smear (79% sensitivity for mild dyskaryosis or worse). The positive predictive value of a borderline smear was only 3.1%. Eleven high-grade lesions were negative by the PCR HPV test (sensitivity 74%). The first generation Hybrid Capture II test had a similar sensitivity but an unacceptably high false positive rate (18.3%), while the newer Hybrid Capture II microtitre kit had a 95% sensitivity and a 2.3% positivity rate in normal women when used at a 2 pg ml(-1) cut-off (positive predictive value 27%). Cytology performed very well in this older cohort of women. The newer Hybrid Capture II microtitre test may be a useful adjunct, especially if the results reported here are reproducible in other studies. A combined screening test offers the possibility of greater protection and/or longer screening intervals, which could reduce the overall cost of the screening programme.

Comparison of PCR- and hybrid capture-based human papillomavirus detection systems using multiple cervical specimen collection strategies.

This study compared the performances of three human papillomavirus (HPV) detection tests with specimens collected by three alternative procedures. The HPV tests included the Hybrid Capture Tube test (HCT), the microplate-based Hybrid Capture II test (HC II), and the MY09-MY11 L1 consensus primer PCR-based assay. Initial cervical specimens were collected from study subjects with a broom device, and after Papanicolaou smears were made, residual specimens were placed into PreservCyt (PC), a liquid cytology medium. A second specimen was collected from each subject and placed into Digene Specimen Transport Medium (STM). The device for collection of the second specimen alternated with consecutive subjects between a conical cytology brush and a Dacron swab. At the 1.0-pg/ml cutoff, the results of the HC II agreed well with those of the PCR. Specifically, when PCR data were restricted to the types found by the HC II (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68), there was greater than 90% agreement between the HC II and PCR results with both STM and PC. At a lower cutoff (0.2 pg/ml), HC II-positive results increased further, especially when the test was applied to the PC specimens. However, false-positive HC II results were more often observed at the 0.2-pg/ml cutoff. HC II yielded the highest HPV positivity with specimens placed into PC, followed by specimens collected with a conical brush and placed into STM and, last, by those collected with a Dacron swab and placed into STM. Our results demonstrate the utility of both the STM and PC specimen collection methods and show good agreement between the HC II and PCR.

Human papillomavirus detection in cervical intraepithelial neoplasia by the second-generation hybrid capture microplate test, comparing two different cervical specimen collection methods.

BACKGROUND: The second generation Hybrid Capture microplate-based human papillomavirus (HPV) test (HC II) was examined to determine its sensitivity for identification of cervical intraepithelial neoplasia (CIN) by two different cervical specimen collection methods. OBJECTIVES: A cohort of 115 women with a mean age of 34.6 years (SD 9.1), referred to colposcopy with a history of abnormal cytology, was studied to compare HPV prevalence and viral load in low grade CIN vs. high grade CIN. STUDY DESIGN: Prior to the application of acetic acid, cervical specimens were obtained by either method 1 or 2, as follows: method 1: A cotton-tipped swab was applied to the ectocervix and endocervix for a Papanicolaou (Pap) smear. Next, a special cone-shaped cervical brush was applied to the endocervix, the ectocervix, and to the posterior vaginal vault and suspended in 1.0 ml of transport medium for HPV testing. Method 2: a Pap smear was taken with a cyto standard cylindrical cytology brush from the endocervix, and ectocervix, and the remaining cells were suspended in 3 ml phosphate-buffered saline (PBS) for HPV testing. Next, a Dacron-tipped swab was used to take a specimen from the ectocervix and posterior fornix and suspended in the same PBS solution.

Reflex human papillomavirus deoxyribonucleic acid testing in women with abnormal Papanicolaou smears.

OBJECTIVE: The study examined interrelationships between sensitivity and specificity of "reflex human papillomavirus deoxyribonucleic acid testing" from liquid-based cervical cytologic specimens by means of receiver operator characteristics curves. STUDY DESIGN: A cohort study was performed on 265 women evaluated by colposcopy because of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion found on Papanicolaou smear. RESULTS: At a positive threshold of 0.2 pg/ml (1000 copies of human papillomavirus per test), human papillomavirus deoxyribonucleic acid testing detected 86% of women with cervical intraepithelial neoplasia and 93% of women with high-grade cervical intraepithelial neoplasia with a specificity of 30%. Decreasing the sensitivity of the human papillomavirus test to 1 pg/ml (5000 copies of human papillomavirus per test) improved the specificity of a positive result to 44% but decreased the clinical sensitivity to 78% for cervical intraepithelial neoplasia grade 2 or 3. Relationships between sensitivity and specificity were influenced by patient age and referral diagnosis. For example, limiting the analysis to only women with a referral for atypical squamous cells of undetermined significance found on Papanicolaou smear and a positive human papillomavirus test threshold of 0.5 pg/ml produced a sensitivity of 90% for cervical intraepithelial neoplasia grade 2 or 3 and a test specificity of 55%. CONCLUSION: Human papillomavirus deoxyribonucleic acid testing of residual cellular material from liquid cytologic specimens appears to be more appropriate for older women (>30 years old) and women with atypical squamous cells of undetermined significance, as opposed to low-grade squamous intraepithelial lesion, on their Papanicolaou smears.

[Cytologic prints of primary and metastatic melanomas. Preliminary report]. / Cytologiczny obraz odbitkowy pierwotnych i przerzutowych czerniaków zlosliwych. Doniesienie wstepne.

In 15 cases of melanoma (10 primary tumours and 5 metastatic ones) imprint examination was performed intraoperatively. In one case the material was non-diagnostic. Out of the remaining 14 cases six tumours consisted of epithelioid cells, one--spindle-shaped and seven were of mixed structure. Typical characteristics of the imprint included cellular dispersion, polymorphism, presence of binuclear and giant cells as well as intranuclear cytoplasmic inclusions. There features are the same as those described in other cytologic studies of these neoplasms. The imprints method turned out to be useful as an accessory and complementary study intraoperative histopathologic examination.

[Use of an immunoenzyme method with monoclonal antibodies in cytologic studies for the optimal diagnosis of non-Hodgkin's lymphoma in children]. / Zastosowanie metody immunoenzymatycznej z uzyciem MoP w badaniach cytologicznych do optymalizacji diagnostyki non-Hodgkin-lymphoma u dzieci.

From January 1987 to April 1988 six children we studied cytologically with the use of alkaline phosphatase-anti-alkaline phosphatase (APAAP) method and monoclonal antibodies (MoP) in order to establish the diagnosis of Non-Hodgkin Lymphoma. (NHL). Cytologic studies concerned pleural fluid (3 patients) imprints of the lymph node (3 patients), bone marrow smears (2 patients) and cerebrospinal fluid (1 patient). We performed simultaneously routine cytologic and histopathologic studies of the lymph nodes. Antigen T6 (thymocytes) was present in blasts of all patients, which permitted us to classify the blasts as common stage II group according to Reinherz. In all cases we found at least two positive antigen detected by MoP pan T (CD2, CD3, CD5, CD7) in one case--no expression of antigen T3 (CD3) and in two cases no antigen detected by an antibody CD2. Antigen Ia was found in one patient, and weak expression of antigen CALLA (CD10) in one patients. In three patients we showed a simultaneous expression of antigens T4, T8, whereas in two patients they were not observed. One child possessed mature phenotype T4, T6. By using APAAP method with MoP in cytologic studies it was possible to diagnose T-lymphoblastic lymphoma in six children before the results of histopathologic examination of the lymph nodes.