Usefulness of hybrid capture HPV DNA assay as a diagnostic tool for human papillomavirus infection

The purpose of this study was to determine the usefulness of the hybrid capture HPV DNA assay, a new nonradioactive solution hybridization assay, as a diagnostic tool for human papillomavirus infection. In a total of 234 women, samples for the hybrid capture assay and polymerase chain reaction (PCR) assay were obtained by wiping a swab across the cervix and external os (either a Dacron swab or a cotton swab was used). The papanicolaou smear test (Pap smear) was carried out on all 234 women. Tissue samples for biopsy were obtained by colposcopy from 118 of the women. Fisher exact test was used for statistical analyses. Using the hybrid capture assay, HPV DNA of high- and intermediate-oncogenic-risk type was detected in 23 (13.9%) of 166 samples from women with Pap smear Class I or II, and 48 (70.6%) of 68 with Pap smear Class III, IV or V (p < 0.0001). The HPV DNA type was detected in 18 (29.0%) of 62 samples from those with no evidence of cervical intraepithelial neoplasia and 44 (78.6%) of 56 with cervical intraepithelial neoplasia or squamous cell carcinoma (p < 0.0001). Correlation of the test results between the hybrid capture test and PCR was determined by using the 217 samples in which both test results were available (PCR test results were not obtainable in 17 samples. When PCR is set as a gold standard, the hybrid capture test has high sensitivity (74.6%) and specificity (92.7%). These findings suggest that the hybrid capture HPV DNA assay is a useful method for diagnosing HPV infection in the clinic.     

The detection of human papillomavirus in papillomas of the larynx and tonsils through immunohistochemistry and DNA in situ hybridization]

Presenting a study about Human Papillomavirus (HPV) determination by immunohistochemistry and "in situ" hybridization, in 25 samples of squamous cell papillomata (15 tonsilar and 10 laryngeal lesions). Five cases resulted positive for HPV: 2 of them for immunohistochemical probes, other 2 for "in situ" hybridization and only 1 cas showed its positivity for both techniques. All these samples belonging to laryngeal cases. No significant differences were found in antecedents, clinical and histological features related with results obtained. Two patients developed a laryngeal carcinoma after papilloma and they had positive "in situ" hybridization. Literature about diagnosis of HPV-infection was revised.     

A comparison of human papillomavirus detection rates by dot blot assay from smear and biopsy specimens with regard to human papillomavirus type and histologic diagnosis

Colposcopic biopsy and cervical smear sampling techniques for human papillomavirus (HPV) DNA dot hybridization were compared to reveal differences related to the level of the histopathologic detection of HPV type 16. The authors used a previously published dot blot assay to analyze 814 pairs of concurrent biopsy and smear DNA specimens for the presence of DNA of HPV 6, 11, 16, and 18. The overall HPV detection rate was 38%, the most prevalent type being HPV 16 (39% of all HPV-positive cases). In detection and typing of HPV DNA, a 81% concordance (658 of 814 pairs) was noted between the smear and biopsy specimens, with a significant correlation in detection of any of the HPV types in the specimens (kappa, .609). The rate of smear-negative cases among all biopsy-positive cases was similar for HPV 11 and HPV 16 (41% and 42%, respectively). Further analysis of distribution of the smear-negative and biopsy-positive cases among different histopathologic levels of disease showed no significant difference between neoplastic and nonneoplastic lesions for either virus type. In 56 cases, only the smear specimen was positive for DNA of the studied HPV types. Both biopsy and smear specimens should be used for HPV detection in cervical dysplasias.     

Adenoid basal epitheliomas of the uterine cervix: a reevaluation of distinctive cervical basaloid lesions currently classified as adenoid basal carcinoma and adenoid basal hyperplasia

A series of 12 adenoid basal carcinomas and three adenoid basal hyperplasias of the cervix were analyzed. The ages of the patients with adenoid basal carcinoma ranged from 30 to 91 years with a mean of 71 years. Pap smear results for 11 of 12 (92%) were abnormal. Almost all patients were asymptomatic. None had a gross cervical tumor. All tumors had typical histologic features of adenoid basal carcinoma, with various degrees of squamous differentiation. Depth of tumor invasion ranged from 2 mm to 10 mm (mean, 4.3 mm; median, 3.7 mm), exceeding 3 mm in six tumors (50%). Tumor volume was >500 mm3 in four tumors (33%). An associated neoplastic squamous lesion was present in 92% of patients, including high-grade cervical intraepithelial neoplasia in 10 cases and microinvasive squamous cell carcinoma in one. Treatment was predominantly surgical, usually after some form of cervical conization; conization alone was performed in three patients. Lymph nodes were removed in five patients; none of 104 nodes had metastases. No recurrence of tumor developed in any patient. Nine patients were alive without disease after 4 to 82 months (mean, 30 months), and three died without disease after 24, 63, and 87 months. The three patients with adenoid basal hyperplasia also were asymptomatic and did not have a gross cervical lesion. Pap smear results for two patients were abnormal. The adenoid basal hyperplasias were incidental, very superficial lesions that resembled small adenoid basal carcinomas. Generally, they were attached to the squamous or endocervical mucosal epithelium; all were less than 0.5 mm in depth. Treatment was hysterectomy in one patient and conization in two. Follow-up was short but uneventful. Our findings, together with those previously reported, indicate (1) adenoid basal carcinoma with typical histologic features is not a malignant neoplasm in that it typically presents in asymptomatic women, usually is discovered after an abnormal Pap smear result due to cervical intraepithelial neoplasia, does not produce a grossly visible lesion, has never metastasized to regional lymph nodes or elsewhere, and has never itself caused death; (2) rare, histologically atypical tumors with distinctly malignant features should not be regarded as adenoid basal carcinoma; and (3) adenoid basal hyperplasia probably is a small adenoid basal carcinoma. We propose the term "adenoid basal epithelioma" to replace adenoid basal carcinoma and adenoid basal hyperplasia, because it better describes the clinicopathologic features of these distinctive lesions and their excellent prognosis and may reduce the likelihood of unnecessarily aggressive treatment.     

Update on the Papanicolaou smear: new issues for the 1990s

The Papanicolaou (Pap) smear is a complex examination that has undergone refinement in recent years. It is now widely accepted that a false-negative rate of perhaps 10 to 20% is inevitable for a variety of reasons. The diagnosis of "atypical cells of undetermined significance" is not a benign diagnosis and is often followed by a more severe lesion on follow-up. The Pap smear appears to be an inefficient method for detecting glandular neoplasms, and clinical features remain the most important diagnostic clue. A Pap smear and cervical biopsy should correlate in 75% or more of cases. In cases of noncorrelation, a positive Pap smear diagnosis is supported in the vast majority of cases.     

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The developed or less developed countries where basic conditions for the screening of cervical cancer are quite different in terms of essential factors such as accuracy of cytology, cost effectiveness and development of new methods of diagnosis. Considering these factors the screening program made by annual Pap smear with adjunctive cervicography and HPV DNA test in the women aged from 20 to 69 years may have universal validity.     

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.     

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Genital human papillomavirus (HPV) infection is the major causal factor of cervical intraepithelial neoplasia (CIN). The potential role of nutrition as an additional, independent risk factor for CIN has not been appropriately addressed in the context of HPV. This case-control study evaluated the etiologic role of HPV in terms of viral type and load and examined the association between CIN and plasma levels of micronutrients adjusting for HPV. Cases (n = 378) with histo-pathologically confirmed CIN and controls (n = 366) with no history of abnormal Pap smears were recruited from colposcopy and gynecology clinics, respectively. Risk of CIN was significantly increased among women who were infected with multiple HPV types (odds ratio [OR] = 21.06), a high viral load (OR = 13.08) and HPV 16 (OR = 62.49). After adjusting for HPV positivity and demographic factors, there was an inverse correlation between plasma alpha-tocopherol and risk of CIN (OR = 0.15). Plasma ascorbic acid was protective at a high level of > or = 0.803 mg/dl (OR = 0.46). CIN was not associated with plasma retinol and beta-carotene levels. The effect of genital HPV infection on CIN development is highly influenced by oncogenic viral type and high viral load. Vitamins C and E may play an independent protective role in development of CIN that needs to be confirmed in prospective studies.     

Gender differences in relation to motivation and compliance in cardiac rehabilitation

OBJECTIVE: The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment. STUDY DESIGN: Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases. RESULTS: HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive. CONCLUSION: DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.     

Quality of life of women with stress urinary incontinence with or without pollakiuria]

BACKGROUND: The optimal management of low grade Papanicolaou (Pap) smear abnormalities remains controversial. This center's experience with recommending cytologic follow-up for women with atypical cells of undetermined significance (ASCUS) or low grade squamous intraepithelial lesions (LSIL) was reviewed to determine outcome and patient/physician compliance. METHODS: The records were reviewed on women with Pap smears reported as either ASCUS (320) or LSIL (112) who did not have a history of dysplasia. The cytologic and colposcopic follow-up for a 2-year period was obtained from the laboratory data base that includes the colposcopy and cancer referrals for this region. Repeat Pap smear in 6 months was recommended. If patients subsequently demonstrated high grade SIL (HSIL) or persistent ASCUS or LSIL over three time intervals, colposcopic evaluation was recommended. RESULTS: The outcome was determined by the most significant diagnosis among the follow-up Pap smears or colposcopic biopsies. 29% of patients were lost to follow-up. Of the remaining patients, 70.5% reverted to normal or benign cellular changes, 25.3% persisted as ASCUS or LSIL, and 5.2% progressed to HSIL. The majority of patients (68%) were referred for colposcopy for persistent mildly abnormal Pap smears. The timing of referral ranged from 3-30 months. CONCLUSIONS: These results suggest that cytologic follow-up of women with low grade Pap smear abnormalities will identify a large number whose smears will regress to normal. A small but significant proportion of women showed subsequent HSIL. Most HSIL was detected within 1 year of the initial abnormal Pap smear and the majority of intervening Pap smears also were abnormal. Approximately one third of patients did not have follow-up within the study system and their outcome was uncertain. Although the recommendations are standard, patterns of follow-up and referral to colposcopy varied widely, suggesting that the guidelines need to be reinforced to both patients and physicians. [See editorial on pages 1-4, this issue.]     

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   

Heterogeneity of human papillomavirus DNA in a patient with Bowenoid papulosis that progressed to squamous cell carcinoma

Bowenoid papulosis (BP) of the genitalia, characterized by the histological findings of a squamous cell carcinoma, follows a largely benign clinical course. The detection of oncogenic human papilloma viruses (HPV) from BP points to an aetiological role of these viral infections. A 47-year-old man with multiple genital skin lesions was seen over a 10-year period with the diagnosis of BP. Recently, he attended again with a recurrent genital tumour that was diagnosed as squamous cell carcinoma. His genital lesions progressed and became polymorphic in appearance, from a wart-like tumour to a reddish invasive plaque. To screen for the presence of different HPV sequences from different skin lesions and to correlate each HPV type with distinct clinical manifestations, polymerase chain reaction and single-strand conformational polymorphism (PCR-SSCP) were performed. PCR-SSCP revealed the presence of several types of HPV from different genital lesions. Sequencing results disclosed that he had a mixed infection of HPV6b, HPV16, HPV18 and HPV33, respectively. Interestingly, the clinical findings were fairly well correlated with the oncogenic potential of HPV found from each lesion.     

Natural history of false-negative papanicolaou smears: a prospective study using screening colposcopy in addition to cytology

The regular Papanicolaou (Pap) smear is cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high rate of false-negative results; therefore, serial examinations are necessary for optimal sensitivity. The sensitivity of the routine pelvic examination is further increased with the addition of colposcopy to cytologic screening. Patients identified as having disease by colposcopy and biopsy but not by Pap smear (false-negative), are followed up, and the progression of their disease is documented until the Pap smear reflects the known change. A total of 276 patients whose Pap tests showed "no abnormal cells" and mild dysplasia (CIN-1 [cervical intraepithelial neoplasia]) by colposcopy and biopsy, who opted not to be treated, were followed up as a function of time. The results of the Pap test on the 276 patients progressed to a low-grade squamous intraepithelial lesion (LGSIL) or higher within 42 months. In this study, false-negative Pap tests that were identified by simultaneously performed colposcopy became positive within 42 months; therefore, careful repetitive screening is necessary. The author argues that a definitive, prospective study on the addition of colposcopy or similar adjunct procedure to the routine pelvic examination, in selected cases, is needed.     

The impact of multiple bereavement in a gay male sample

In this study we explore the biographical disruption resulting from a diagnosis of an abnormal Pap smear and the consequent process of biographical reconstruction. This is a qualitative study of thirteen women between the ages of 19 and 54 years who were diagnosed with an abnormal Pap smear and underwent colposcopy treatment. Data collection was through individual in-depth interviews, which were transcribed and analyzed by a team of researchers for important themes. An opportunistic sampling strategy was used. The inherent ambiguity in the diagnosis, its treatment strategies, the prognosis of their condition, and patients' fear of cancer all made the process of biographical reconstruction more problematic. By putting their faith in medicine and mobilizing their personal resources, women attempted to reestablish a positive personal and social self. Further exploration of the long-term psychosocial impact of this diagnosis is warranted so that women's emotional as well as medical needs are adequately addressed.     

Pap smear screening in an urban STD clinic. Yield of screening and predictors of abnormalities

BACKGROUND: Pap smear screening studies in STD clinics have reported high rates of squamous intraepithelial lesions (SIL); however, there are limited data on levels of unsatisfactory smears of characteristics associated with cytologic abnormalities. GOAL: To assess the yield to Pap smear screening in an STD clinic and to evaluate the rates of and risk factors for atypia, low-grade SIL (LSIL), and high-grade SIL (HSIL). STUDY DESIGN: A chart review of the clinic records of women undergoing Pap smear screening between 1991 and 1994 was conducted. Results were assessed from two different screening protocols, the first using a Dacron swab to obtain the endocervical sample and the second using a cytobrush. RESULTS: Of 2034 Pap smears, 1313 (64.6%) were negative, 202 (9.9%) were unsatisfactory, 257 (12.6%) were atypical, 211 (10.4%) had LSIL, and 51 (2.5%) had HSIL. With the change to the cytobrush protocol, the rate of unsatisfactory smears decreased from 14.4% to 3% (p < 0.001), atypia increased from 10% to 16.7% (p < 0.001), and HSIL rose from 1.7% to 3.7% (p < 0.001). By multivariate analysis, atypia was associated with genital warts (odds ratio (OR) 1.53, 95% confidence interval (CI): 1.16-2.02); LSIL with younger age (p < 0.001, for trend), black race (OR 1.51, 95% CI: 1.08-2.10), genital warts (OR 1.81, 95% CI: 1.33-2.47), and an abnormal appearance of the cervix on examination (OR 2.49, 95% CI: 1.85-3.35); and HSIL with a previous abnormal Pap smear (OR 2.48, 95% CI: 1.08-2.10). Overall, abnormality rates were significantly higher in adolescents (35.5%) than older women (21.7%) (p < 0.01). CONCLUSIONS: Obtaining satisfactory Pap smears among women undergoing screening in an STD clinic is feasible and cytologic abnormalities are common. These results continue to support the need for Pap smear screening in STD clinics, but the high rates in adolescents, a group in whom the natural history of cytologic abnormalities has not been well-defined, raise questions about the need to develop age-appropriate screening and management strategies.     

Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players

BACKGROUND: There is an increasing number of articles regarding the long term follow-up of Papanicolaou (Pap) smears with the diagnosis of atypical squamous cells of undetermined significance (ASCUS). Much controversy exists regarding the management of patients with this diagnosis. In a prior study in 1992, the authors performed automated rescreening of 101 ASCUS cases and 91 negative (control) cases. They found that through PAPNET-directed rescreening, 35 of 101 ASCUS cases (35%) could be reclassified as a squamous intraepithelial lesion (SIL). METHODS: These 192 women were followed since 1992 through manual look backs of subsequent Pap smears and surgical biopsies over a 4-year period. The population studied was comprised of predominantly black women between the ages of 14 and 85 years. The majority were considered a high risk population because many had a history of several sexual partners and multiple pregnancies. RESULTS: Eighteen of 74 patients (24.3%) with an original diagnosis of ASCUS were found on subsequent Pap smears to have an SIL. Only 4 of 64 patients (6%) who originally had a negative Pap smear subsequently were found to have a low grade squamous intraepithelial lesion (LGSIL) within 4 years. Through ordinal logistic regression analysis, it was found that patients with an ASCUS diagnosis had a risk of developing SIL that was 2.6 times greater than the risk for patients with a negative smear diagnosis. Comparing the surgical biopsies in the control and ASCUS groups, there was no statistically significant difference in the risk of developing SIL. This may be because the number of follow-up biopsies were small. CONCLUSIONS: A statistically significant difference of the risk of developing SIL exists between patients with a negative smear versus those with an ASCUS smear. Long term follow-up is essential in the management of the patients with an ASCUS smear because there is clearly an increased risk of developing SIL.     

Hantavirus pulmonary syndrome treated with inhaled nitric oxide

BACKGROUND: A retrospective study was done to assess the correlation between endometrial cells on routine cervical cytology and carcinoma of the endometrium. METHODS: In a 4-year period, endometrial cells of some type were identified on the Papanicolaou (Pap) smears of 61 women, of whom 52 had further diagnostic evaluation of the endometrium. Data were analyzed with a multivariate stepwise logistic regression. RESULTS: The results indicated an association of endometrial cells in Pap smears with carcinoma of the endometrium in seven patients (13.5%). In 45 patients (86.5%), the final diagnosis was benign. Factors that impacted the diagnosis of carcinoma were the findings of atypical or cancerous endometrial cells on Pap smear and abnormal vaginal bleeding. CONCLUSIONS: These data indicate the importance of further diagnostic evaluation with endometrial sampling in postmenopausal patients with endometrial cells seen in Pap smears, especially those with abnormal bleeding.     

Evaluation of the ThinPrep Pap test as an adjunct to the conventional Pap smear

OBJECTIVE: To evaluate the ThinPrep Pap test as an adjunct to the conventional Pap smear. DESIGN AND SETTING: Prospectively collected cervical samples were split for independent screening at a large specialised private gynaecological pathology practice in Sydney. MAIN OUTCOME MEASURES: Detection of additional significant abnormalities (cervical intraepithelial neoplasia 1, or more severe); changed management recommendations from "repeat smear in 12 months" or "...six months" to "colposcopy", a reduction in unsatisfactory reports. RESULTS: 35,560 paired (split-sample) conventional and ThinPrep slides were prepared. Significant abnormalities were detected in 724 conventional smears (2%). Additional significant abnormalities were found in 85 ThinPrep slides whose corresponding conventional smear was negative or unsatisfactory even after review, representing a 12% increase in the detection of significant abnormalities. As a result of the addition of ThinPrep, management recommendations were changed from "repeat smear in 12 months" or "...six months" to "colposcopy" for 89 of 1669 women whose conventional Pap smears showed minor non-specific changes or papillomavirus. There were 1258 conventional smears (3.5%) that were unsatisfactory compared with 235 ThinPrep slides (0.7%); for only 74 samples (0.2%) were both slides unsatisfactory. CONCLUSIONS: The addition of the ThinPrep Pap test improves detection and clinical management of cervical abnormalities, and reduces the number of unsatisfactory samples which would otherwise require repeat tests.     

Detection of human papillomavirus DNA in genital lesions by enzymatic in situ hybridization with Fast Red and laser scanning confocal microscopy

Human papillomavirus (HPV) infection with potentially oncogenic types 16 or 18 is common in genital lesions especially in uterine carcinomas. In such lesions, in situ hybridization with non-radioactive probes is a powerful tool for the histopathologist to detect and type HPV DNA either on cell deposits or on tissue sections. The use of an immunohistochemical method involving alkaline phosphatase and Fast Red TR salt/naphthol AS-MX phosphate is proposed for use with conventional bright-field or fluorescence microscopy as well as by laser scanning confocal microscopy. The alkaline phosphatase-Fast Red reaction has the advantage of producing a red precipitate that permits the detection of in situ hybridization signals by bright-field microscopy, and of obtaining a strong red fluorescence characterized by a lack of bleaching when excited by a green light. Therefore, the alkaline phosphatase-Fast Red reaction is well adapted for observations by fluorescence and confocal microscopy, the latter method allowing the detection, in tissue sections of cervical intraepithelial lesions, of small punctate and large diffuse hybridization signals, considered as integrated and episomal states of HPV DNA respectively. The combination of in situ hybridization with the alkaline phosphatase-Fast Red reaction and confocal microscopy is particularly convincing when hybridization signals are of small size and/or of low fluorescence intensity, especially if they are present in various focal planes; in such conditions, infected cells are easily detected by three-dimensional reconstruction. Therefore, this combination is a suitable method for identifying and characterizing HPV DNA in cells and tissue sections.     

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Human papillomavirus (HPV) is associated with benign cutaneous or mucosal lesions and with malignant tumours, but none of the HPV types has so far been related to skin tags. Skin biopsy specimens from 49 Caucasian patients suffering from the presence of multiple soft fibromas were analysed by means of dot blot hybridization and by polymerase chain reaction assays aimed at detecting all known HPV types. The results revealed the presence of HPV DNA type 6/11 in 88% of the skin tags examined. This result supports the hypothesis that HPV plays a part in the progression of cutaneous soft fibromas, as previously reported for laryngeal papillomas.