Human papillomavirus is detectable in Barrett's esophagus and esophageal carcinoma but is unlikely to be of any etiologic significance.

UNLABELLED: Barrett's esophagus (BE), a known precursor of esophageal adenocarcinoma has recently been associated with human papillomavirus (HPV). p16(INK4a) expression is a recognized surrogate marker of HPV infection in the cervix. OBJECTIVES: This study has assessed the possible role of human papillomavirus (HPV) infection in BE and esophageal adenocarcinoma, in the North American population by screening esophageal tissues for HPV by a combination of assays. STUDY DESIGN: Formalin-fixed, paraffin-embedded blocks from cases of Barrett's esophagus (n=84), esophageal adenocarcinoma (n=36) and normal gastro-esophageal junction (n=29) were examined for HPV by PCR, chromogenic in situ hybridization, and p16(INK4a) immunohistochemistry. RESULTS: HPV DNA was detected by PCR in 23 of 84 (27.4%) BE cases, 11 of 36 (31%) cases of adenocarcinoma and in 7 of 29 (24%) normal control cases (p=0.82). p16(INK4a) staining was positive in 10 (12%) cases of BE, 15 (42%) cases of adenocarcinoma and 6 (21%) cases of the control group. Positive p16(INK4a) staining was not statistically different between the three groups whether positive or negative for HPV DNA (p=0.91 and p=0.91 respectively). Similarly, negative p16(INK4a) staining did not show a difference between the three groups for whether positive or negative for HPV DNA (p=0.50 and p=0.28, respectively). HPV was not detected by CISH in the adenocarcinomas while in BE and control groups, CISH was non-contributory. CONCLUSIONS: These data suggest that while HPV is detectable in a subset of esophageal lesions and tumors, the HPV detected is unlikely to be of etiologic significance or a factor accounting for the increase in BE and esophageal adenocarcinoma cases in the United States.

HPV DNA is associated with a subset of Schneiderian papillomas but does not correlate with p16(INK4a) immunoreactivity.

This study investigated the role of human papillomavirus (HPV) in Schneiderian papillomas (SPs) to determine whether HPV is associated with the pathogenesis of particular histologic subtypes and whether p16(INK4a) can be used as a surrogate marker for HPV detection. Twenty-seven papilloma specimens (19 inverted [IPs], 6 exophytic [EPs], 1 oncocytic [OP] and 1 mixed) were collected from 23 patients. Purified SP DNA extracts were tested for HPV by PCR using GP5 +/GP6 + primers; HPV genotyping was performed by dot blot hybridization. PCR positive specimens were screened for HPV by biotinyl-tyramide-based chromogenic in situ hybridization (CISH). Immunohistochemsistry (IHC) for the HPV L1 capsid protein and for p16(INK4a) was performed on all specimens. HPV was detected by PCR in 16/27 (59.3%) SPs; 9/19 (47.4%) IPs; 6/6 (100%) EPs [p = 0.051], and 1/1 (100%) mixed SP. HPV was not detected in the single OP. High risk genotypes were detected in 4/9 IPs (44.4%) and 0/6 EPs (0%) [p = 0.10]. Seven of 16 PCR positive SPs were also CISH positive for HPV: 5/6 EPs (83.3%) and 1/9 IP (11.1%) [p = 0.01]. IHC for the L1 capsid protein was positive in 2 SPs (1 EP and 1 mixed). p16(INK4a) staining was seen in 14/16 (87.5%) PCR positive SPs and in 10/11 (90.9%) PCR negative SPs (p = 1.00). In summary, this study demonstrates a strong association between HPV and EPs, however, its role in IPs remains less well-defined. Further, p16(INK4a) is not a useful surrogate marker for HPV detection across the various SPs.

Evidence of HPV16 integration in low- and high-grade cervical lesions that regress demonstrated by multiple displacement amplification and Southern blot hybridisation.

The prevalence and significance of human papillomavirus (HPV) integration among different grades of cervical lesions is uncertain. In this study, HPV physical status was examined by the combination of multiple displacement amplification (MDA) with Southern blot hybridisation (SBH). DNA extracts from 95 cervical cytology samples (NILM, ASC-US, LSIL, ASC-H, HSIL) were subject to whole genome amplification by MDA followed by SBH with [alpha-(32)P]-labelled HPV probes. Mixed HPV16 episomal/integrant sequences were detected in three ASC-US patients (two diagnosed with benign changes and one with cervical intraepithelial neoplasia (CIN)2/3 after biopsy follow-up), one ASC-H patient with CIN2/3 histological diagnosis, and one HSIL patient with benign changes. Additional follow-up cytological data available for three of these patients demonstrated series of lesion-free samples. The data support the view that integration can occur in low-grade lesions and that lesions with mixed episomal/integrant HPV can regress.

High-risk human papillomavirus type does not predict grade of cervical intraepithelial neoplasia.

PURPOSE OF INVESTIGATION: The aim of this study was to examine whether HPV testing specificity for cervical intraepithelial neoplasia (CIN) grades 2 or 3 could be improved by restricting the range of HPV types classified as 'high-risk'. METHODS: DNA was extracted from 28 CIN I, nine CIN II and 13 CIN III formalin-fixed, paraffin-embedded biopsies. HPV type was determined by General Primer mediated 5+/6+ PCR assay. RESULTS: The prevalence of specific HPV types among the different grades of CIN and the relationship to the referral smear diagnosis was examined. HPV type-16 alone was more highly associated with CIN grade (p < 0.0001; Specificity = 0.93; Sensitivity = 0.68) than was the group of HPV types collectively classed as high-risk (p = 0.025; Specificity = 0.23; Sensitivity = 1.00). CONCLUSIONS: These data suggest HPV testing specificity could be improved simply by including a separate test for HPV-16. In conjunction with previous studies, the data also suggests redefinition of the high-risk HPV category to take into account the differing degrees of oncogenicity of high-risk HPV types.

Allelic imbalance is not restricted to numerically abnormal chromosomes in epithelial ovarian tumours.

In this study, 23 low malignant potential (LMP) and 27 invasive epithelial ovarian tumours have been examined by microdissection and microsatellite polymerase chain reaction (PCR) for allelic imbalance (AI) at loci on the p and q arms of chromosomes 1, 11, 17, and X, and the data have been compared with interphase cytogenetics for numerical abnormalities (aneusomy) of these chromosomes. AI was uncommon in LMP tumours (5 of 23 at 9 of 146 informative loci) but was significantly more common (p<0.001) in invasive carcinomas (21 of 27 at 47 of 168 informative loci). This difference remained when LMP tumours were compared specifically with stage I carcinomas (p<0.001). A greater number of loci were involved in AI amongst serous than amongst mucinous carcinomas (p=0.015). AI was present at significantly more loci in carcinomas showing aneusomy by interphase cytogenetics than in those showing no numerical chromosome abnormalities (p<0.001). However, amongst the carcinomas showing aneusomy, AI was as frequent at loci on chromosomes with no numerical abnormality as at those with the numerical changes. These data demonstrate that aneusomy and AI are interrelated phenomena but that AI does not occur simply as a consequence of numerical chromosome changes.

Antimetastasis gene expression and numerical chromosomal abnormalities of chromosomes 1 & 17 in serous tumours of the ovary.

OBJECTIVE(S): The aim of this study was to examine the expression of the antimetastasis gene nm23 and numerical changes on chromosome 1 and 17 in ovarian tumours. METHODS: In this study 20 serous cystadenocarcinomas, ten borderline and five benign tumours were analysed for expression of the nm23 antimetastasis gene by immunohistochemistry and for numerical chromosomal abnormalities of chromosomes 1 and 17 by interphase cytogenetics. RESULTS: Strong intracytoplasmic immunoreactivity with the antimetastasis gene was observed in late stage carcinomas but not in benign or borderline tumours or in lymph node metastases. Numerical abnormalities were only observed in carcinomas. CONCLUSION(S): These sets of data are consistent with the majority of benign and borderline tumours lacking invasive potential. Odds Ratio (OR) assessment indicates that the presence of numerical aberrations correlates with immunopositivity.

Influenza immunizations in the elderly: a continuous quality improvement project.

UNLABELLED: As part of the continuous quality improvement program at The Toronto Hospital's Department of Family & Community Medicine (TTH-DFCM), it was considered necessary to examine the structures, processes and outcomes of influenza immunization for the elderly. OBJECTIVE: The study sought to (a) document the current influenza immunization process; (b) quantify influenza immunization rates for elderly patients during two consecutive immunization seasons (1996 and 1997), and compare these rates across physician teams, attending staff vs. residents, patient gender, and patient age groups; (c) compare influenza immunization rates with other centers; and (d) identify barriers and propose solutions to improve influenza immunization rates in the elderly. DESIGN: Evaluation Formative Research. SETTING: A computerized roster of 15,000 patients at The Toronto Hospital, Department of Family and Community Medicine, a University of Toronto academic teaching center. PARTICIPANTS: Active patients age 65 years and over. DEPENDENT VARIABLE: Influenza immunization. INDEPENDENT VARIABLES: Physician Teams, Physician status, Patient gender, and Patient age group. RESULTS: Immunization rates of attendees increased from 75.4% to 78.7%; over 3% increase from 1996 to 1997. Major subgroups which benefited from increased immunization rates were patients in the Blue team, patients age 70-74 years, and female patients. CONCLUSION: This study presents a rigorous examination of the components of the influenza immunization program, and demonstrates improved immunization rates over a two-year period. Suggestions for future action have been identified. The study design can also serve as a model for future clinical quality improvement projects.

Basal keratinocyte tetrasomy in low-grade squamous intra-epithelial lesions of the cervix is restricted to high and intermediate risk HPV infection but is not type-specific.

Human papillomavirus (HPV) infection appears to be an early event in cervical carcinogenesis with additional abnormalities being required for biological transformation. We have analysed 179 low-grade cervical squamous intra-epithelial lesions (SILs) and 15 normal cervices for the presence of HPV using both in situ hybridization and polymerase chain reaction (PCR). PCR was performed with GP5+/GP6+ primers followed by hybridization using probes for low (HPV 6, 11, 40, 42, 43, 44), intermediate (HPV 31, 33, 35, 39, 51, 52, 58, 59, 66 and 68) and high-risk HPVs (HPV 16, 18, 45 and 56). Interphase cytogenetic analysis using pericentromeric probes for chromosomes 1, 3, 4, 6, 10, 11, 17, 18 and X was also performed to identify numerical chromosomal abnormalities. Tetrasomy of all nine chromosomes was identified within basal keratinocytes, was restricted to epithelia infected with high risk (17 of 46) or intermediate risk (23 of 83) HPVs but was not HPV type-specific. Tetrasomy was not identified in any of the epithelia infected with low risk HPVs (n = 62). These numbers include multiple infection. These findings indicate that the induction of tetrasomy is a property restricted to high and intermediate-risk HPV types but that it is not type-specific. The factors governing which lesions will develop this abnormality are as yet unclear.