Biomedical subjects

Mark E Sherman

Publications and source records attributed to Mark E Sherman.

At least 73 records · Page 4Linked to original sources

PubMed2003

A comparison between real-time polymerase chain reaction and hybrid capture 2 for human papillomavirus DNA quantitation.

Studies investigating human papillomavirus (HPV) viral load as a risk factor in the development of squamous intraepithelial lesions (SILs) and cancer have often yielded conflicting results. These studies used a variety of HPV viral quantitation assays [including the commercially available hybrid capture 2 (HC 2) assay], which differ in their ability to account for differences in cervical cell collection, linear dynamic range of viral load quantitation, and determination of type-specific versus cumulative viral load measures. HPV-16 and HPV-18 viral quantitation using real-time PCR assays were performed to determine whether type-specific viral load measurements that adjust for specimen cellularity result in a different association between viral load and prevalent SIL and cancer, compared with HC 2 quantitation (which does not adjust for cellularity or multiple infections). In general, HPV-16 viral load as measured by real-time PCR increased linearly with increasing grade of SIL while HPV-18 measured using similar techniques increased through low-grade SIL (LSIL), with HPV-18 viral load among high-grade SIL and cancers near the level of cytologically normal women. HC 2 viral load, using the clinical 1.0 pg/ml cut point, differentiated cytologically normal women from women with any level of cytological abnormality (normal versus >/=LSIL) but did not change as lesion severity increased. There was no evidence for plateau of HC 2 at high copy numbers, nor was significant variability in total specimen cellularity observed. However, cumulative viral load measurements by HC 2, in the presence of multiple coinfections, overestimated type-specific viral load. Multiple infections were more common among women with no (32%) or LSIL (51%) [versus 23% in high-grade SIL/cancer], partially explaining the lack of a dose response using a cumulative HC2 viral load measure. The nonrandom distribution of multiple infections by case-control status and the apparent differential effect of viral load by genotype warrant caution when using HC 2 measurements to infer viral load associations with SIL and cancer.

Carcinoma, Squamous Cell↗

PubMed2003

A comparison of single and combined visual, cytologic, and virologic tests as screening strategies in a region at high risk of cervical cancer.

Increased understanding of human papillomavirus (HPV) infection as the central cause of cervical cancer has permitted the development of improved screening techniques. To evaluate their usefulness, we evaluated the performance of multiple screening methods concurrently in a large population-based cohort of >8500 nonvirginal women without hysterectomies, whom we followed prospectively in a high-risk region of Latin America. Using Youden's index as a measure of the trade-off between sensitivity and specificity, we estimated the performances of a visual screening method (cervicography), conventional cytology, liquid-based cytology (ThinPrep), and DNA testing for 13 oncogenic HPV types. The reference standard of disease was neoplasia > or = cervical intraepithelial neoplasia grade 3 (CIN 3), defined as histologically confirmed CIN 3 detected within 2 years of enrollment (n=90) or invasive cancer detected within 7 years (n=20). We analyzed each technique alone and in paired combinations (n=112 possible strategies), and evaluated the significance of differences between strategies using a paired Z test that equally weighted sensitivity and specificity. As a single test, either liquid-based cytology or HPV DNA testing was significantly more accurate than conventional cytology or cervicography. Paired tests incorporating either liquid-based cytology or HPV DNA testing were not substantially more accurate than either of those two test strategies alone. However, a possibly useful synergy was observed between the conventional smear and cervicography. Consideration of age or behavioral risk profiles did not alter any of these conclusions. Overall, we conclude that highly accurate screening for cervical cancer and CIN 3 is now technically feasible. The remaining vital issue is to extend improved cervical cancer prevention programs to resource-poor regions.

Adolescent↗

PubMed2003

Determinants of human papillomavirus load among women with histological cervical intraepithelial neoplasia 3: dominant impact of surrounding low-grade lesions.

Measurement of human papillomavirus (HPV) DNA load has been suggested as a means for improving the positive predictive value of HPV testing for detecting cervical intraepithelial neoplasia 3 and cancer (CIN3+). We hypothesized that lesions surrounding CIN3+ (especially the extent of associated CIN1) are important determinants of load, which limit its clinical use. To test this hypothesis, we reviewed the pathology of women at enrollment in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were managed at enrollment with oncogenic HPV testing using Hybrid Capture 2 (Digene Corp., Gaithersburg, MD) or colposcopy. We focused our analysis on 133 cases of CIN3+ that were identified, stratified by the number of HPV types detected using a PCR-based method (62 single, 71 multiple infections). Infection with multiple types (P < 0.01) and identification of CIN1 or CIN2 in tissues surrounding CIN3 (P = 0.01) were each significantly associated with higher load (two-way ANOVA). Higher load was associated with more extensive CIN1 (P < 0.01), especially when associated with multiple HPV types. Intensive partial rescreening of enrollment thin-layer slides obtained from women with histopathological CIN3+ revealed that ASC-US/LSIL cells were more numerous than ASC-H/HSIL cells. ASC-US/LSIL cell counts were significantly correlated with load (r = 0.31; P < 0.01), whereas counts of ASC-H/HSIL cells were uncorrelated. We conclude that the extent of histopathological CIN1, number of HPV types, and the number of ASC-US/LSIL cells in exfoliative cervical samples vary greatly among cases of CIN3+ and strongly affect HPV load. These factors severely limit the clinical use of load measurements irrespective of HPV testing methodology.

Adult↗

PubMed2002

Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States. Results from the SEER Program, 1978-1998.

BACKGROUND: Malignant tumors of the ovary are the leading cause of death from gynecologic malignancies in the United States. Population-based incidence data for these neoplasms by histopathologic type and race are limited. Variation in rates may provide clues for future etiologic studies. METHODS: The authors performed a detailed, population-based analysis of U.S. incidence rates by histologic type, race, and age for invasive ovarian tumors that were diagnosed during 1978-1998 and for borderline ovarian tumors that were diagnosed during 1992-1998 using data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS: White women had significantly higher rates compared with black women of all types of epithelial tumors, with the white:black rate ratios ranging from 1.23 to 2.56. Black women had higher rates of gonadal stromal tumors. Among both white women and black women, total carcinoma rates did not change greatly from 1978-1982 to 1995-1998. Among white women, the reported incidence rates for invasive serous, endometrioid, and clear cell tumors increased during 1978-1998, whereas the rates of mucinous; papillary, not otherwise specified (NOS); and other epithelial tumors declined. Among black women, the reported rates of papillary, NOS tumors decreased significantly, whereas the rates of other tumor types fluctuated. Incidence rates of borderline ovarian tumors were higher among white women compared with black women and did not change significantly during 1992-1998. Serous and mucinous tumors were the predominant tumors reported for women age < 45 years, whereas serous; papillary, NOS; and other epithelial tumors predominated among older women. CONCLUSIONS: Incidence rates for malignant ovarian tumors have remained relatively stable, with higher rates for white women compared with black women. The reported rates for some specific histopathologic tumor types have changed over time, in part reflecting more specific pathologic classification. The possible effect of shifting exposure prevalence on incidence patterns warrants further study.

Adolescent↗

PubMed2002

Absolute risk of a subsequent abnormal pap among oncogenic human papillomavirus DNA-positive, cytologically negative women.

BACKGROUND: The addition of human papillomavirus (HPV) DNA testing to cytologic screening for cervical carcinoma is now being considered. The majority of women in screening cohorts who test positive for oncogenic types of HPV DNA have concurrent negative Pap tests. The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain. METHODS: A subcohort of 2020 women with a negative Pap test who tested positive at enrollment for oncogenic HPV DNA types using the Hybrid Capture 2 Test were followed for 57 months at Kaiser Permanente (Portland, OR). Absolute risks of new abnormal cytologic interpretations were computed using Kaplan-Meier methods. Logistic regression models were used to evaluate determinants of a new abnormal Pap test. RESULTS: The cumulative incidence for a Pap test interpreted as atypical squamous cells or more severe (>or= ASC) was 16.8% (95% confidence interval [CI] = 15.0-18.6%), 6.4% (95% CI = 5.2-7.6%) for low-grade squamous intraepithelial lesions or more severe, and 2.2% (95% CI = 1.5-2.9%) for high-grade squamous intraepithelial lesions or more severe. By comparison, the cumulative incidence of greater than or equal to ASC among HPV-negative women was 4.2% (95% CI = 3.9-4.6%). The highest viral load (100 relative light units per the positive control or greater) was associated with a greater risk of an abnormal Pap test (odds ratio= 2.7, 95% CI = 1.7-4.1) than lower viral loads. CONCLUSIONS: These results suggest that about 15% of women in annual screening programs who concurrently have a negative Pap test and a positive oncogenic HPV test will have a subsequent abnormal Pap test within 5 years. This risk estimate will be useful to the many clinicians and patients likely to be diagnosed with an HPV infection and negative cytology if HPV DNA is added to general screening.

Adolescent↗

PubMed2002

A prospective study of high-grade cervical neoplasia risk among human papillomavirus-infected women.

BACKGROUND: In case-control studies, smoking, parity, and oral contraceptive use have been associated with an increased risk of cervical intraepithelial neoplasia grade 3 (CIN3) and cervical cancer among women who are infected with oncogenic human papillomavirus (HPV). However, these potential risk factors have not been adequately studied in prospective studies. METHODS: We studied 1812 women who were enrolled in a 10-year prospective study of cervical neoplasia at Kaiser Permanente in Portland, Oregon, and who at enrollment had tested positive for oncogenic HPV DNA and had responded to a questionnaire that included questions on smoking, oral contraceptive use, and parity. Absolute risks and crude relative risks (RRs) with 95% confidence intervals (CIs) for CIN3 or cervical cancer were computed for three time intervals (0-8, 9-68, and 69-122 months after enrollment) using the Kaplan-Meier method. Conditional logistic regression models were used to control for factors that may have influenced our risk estimates, specifically the cytologic interpretation of baseline Pap smear, number of Pap smears during follow-up, age at enrollment, age at prediagnosis visit, and age at diagnosis. All statistical tests were two-sided. RESULTS: Oral contraceptive use and parity were not associated with risk of CIN3 or cervical cancer. Former smokers, women who smoked less than one pack of cigarettes per day, and women who smoked one or more packs per day had crude RRs for CIN3 or cervical cancer for the entire follow-up period of 2.1 (95% CI = 1.1 to 3.9), 2.2 (95% CI = 1.2 to 4.2), and 2.9 (95% CI = 1.5 to 5.6), respectively, compared with never smokers. In the multivariable model, former smokers, women who smoked less than one pack/day, and women who smoked one or more packs/day had RRs of 3.3 (95% CI = 1.6 to 6.7), 2.9 (95% CI = 1.4 to 6.1), and 4.3 (95% CI = 2.0 to 9.3), respectively, for CIN3 or cervical cancer compared with never smokers. CONCLUSIONS: Smoking is associated with an increased risk of invasive cervical cancer in women who are infected with oncogenic HPV. Subsequent studies should examine the role of smoking in the multistage pathogenesis of cervical cancer.

Adult↗

PubMed2002

Type specific persistence of high risk human papillomavirus (HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women: population based prospective follow up study.

OBJECTIVES: To investigate the role of human papillomavirus (HPV) in the development of cervical neoplasia in women with no previous cervical cytological abnormalities; whether the presence of virus DNA predicts development of squamous intraepithelial lesion; and whether the risk of incident squamous intraepithelial lesions differs with repeated detection of the same HPV type versus repeated detection of different types. DESIGN: Population based prospective cohort study. SETTING: General population in Copenhagen, Denmark. PARTICIPANTS: 10 758 women aged 20-29 years followed up for development of cervical cytological abnormalities; 370 incident cases were detected (40 with atypical squamous cells of undetermined significance, 165 with low grade squamous intraepithelial lesions, 165 with high grade squamous intraepithelial lesions). MAIN OUTCOME MEASURES: RESULTS of cervical smear tests and cervical swabs at enrollment and at the second examination about two years later. RESULTS: Compared with women who were negative for human papillomavirus at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells (odds ratio 3.2, 95% confidence interval 1.3 to 7.9), low grade lesions (7.5, 4.8 to 11.7), or high grade lesions (25.8, 15.3 to 43.6). Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low (34.3, 17.6 to 67.0) and high grade lesions (60.7, 25.5 to 144.0). For high grade lesions the risk was strongly increased if the same virus type was present at both examinations (813.0, 168.2 to 3229.2). CONCLUSIONS: Infection with human papillomavirus precedes the development of low and high grade squamous intraepithelial lesions. For high grade lesions the risk is greatest in women positive for the same type of HPV on repeated testing.

Adult↗

PubMed2002

Comprehensive analysis of human leukocyte antigen class I alleles and cervical neoplasia in 3 epidemiologic studies.

To comprehensively explore the relationship between human leukocyte antigen (HLA) class I alleles and cervical neoplasia, a subset of participants from 3 large US and Costa Rican cervix studies were typed for HLA class I alleles. Study subjects were women with cervical cancer or high-grade squamous epithelial lesions (HSILs; n=365) or low-grade squamous epithelial lesions (LSILs; n=275) or who were cytologically normal (control subjects; n=681). Allele-disease associations were assessed by logistic regression analysis. Consistent associations across all studies were observed for HLA-CW*0202 with a combined odds ratio of 0.53 (95% confidence interval [CI], 0.29-0.89) for cancer or HSILs and 0.58 (95% CI, 0.37-1.04) for LSILs, compared with control subjects and adjusted for study. This finding supports the hypothesis that a single allele may be sufficient to confer protection against cervical neoplasia. Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia.

Alleles↗

PubMed2002

Viral load of human papillomavirus and risk of CIN3 or cervical cancer.

Carcinogenic human papillomaviruses (HPV) are thought to be necessary for development of cervical cancer. We assessed whether higher viral loads of such viruses predicted future risk of CIN3 or cancer (CIN3+) in a cohort of 20810 women followed up for 10 years with cytological screening. We measured the viral load for 13 types of carcinogenic HPV (relative light units normalised to 1 pg/mL HPV 16 positive controls [RLU/PC]) using Hybrid Capture 2 testing of cervicovaginal lavages obtained at enrolment. Results were stratified into four groups (RLU/PC 1 to <10, 10 to <100, 100 to <1000, > or = 1000). Although presence of HPV strongly increased risk of CIN3+, high viral load did not further predict risk of CIN3+.

Adolescent↗

PubMed2002

Menopausal hormone replacement therapy and risk of ovarian cancer.

CONTEXT: The association between menopausal hormone replacement therapy and ovarian cancer is unclear. OBJECTIVE: To determine whether hormone replacement therapy using estrogen only, estrogen-progestin only, or both estrogen only and estrogen-progestin increases ovarian cancer risk. DESIGN: A 1979-1998 cohort study of former participants in the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine US clinical centers. PARTICIPANTS: A total of 44 241 postmenopausal women (mean age at start of follow-up, 56.6 years). MAIN OUTCOME MEASURE: Incident ovarian cancer. RESULTS: We identified 329 women who developed ovarian cancer during follow-up. In time-dependent analyses adjusted for age, menopause type, and oral contraceptive use, ever use of estrogen only was significantly associated with ovarian cancer (rate ratio [RR], 1.6; 95% confidence interval [CI], 1.2-2.0). Increasing duration of estrogen-only use was significantly associated with ovarian cancer: RRs for 10 to 19 years and 20 or more years were 1.8 (95% CI, 1.1-3.0) and 3.2 (95% CI, 1.7-5.7), respectively (P value for trend <.001), and we observed a 7% (95% CI, 2%-13%) increase in RR per year of use. We observed significantly elevated RRs with increasing duration of estrogen-only use across all strata of other ovarian cancer risk factors, including women with hysterectomy. The RR for estrogen-progestin use after prior estrogen-only use was 1.5 (95% CI, 0.91-2.4), but the RR for estrogen-progestin-only use was 1.1 (95% CI, 0.64-1.7). The RRs for less than 2 years and 2 or more years of estrogen-progestin-only use were 1.6 (95% CI, 0.78-3.3) and 0.80 (95% CI, 0.35-1.8), respectively, and there was no evidence of a duration response (P value for trend =.30). CONCLUSION: Women who used estrogen-only replacement therapy, particularly for 10 or more years, were at significantly increased risk of ovarian cancer in this study. Women who used short-term estrogen-progestin-only replacement therapy were not at increased risk, but risk associated with short-term and longer-term estrogen-progestin replacement therapy warrants further investigation.

Aged↗

PubMed2002

Use of human papillomavirus DNA testing to compare equivocal cervical cytologic interpretations in the United States, Scandinavia, and the United Kingdom.

BACKGROUND: Human papillomavirus (HPV) DNA testing may be useful in clarifying equivocal cervical cytologic interpretations. One application might be to standardize the meaning of equivocal interpretations from laboratories in various regions. Because international differences may be particularly marked, international comparisons of emerging data will require clear translations of "equivocal" and similar terms. METHODS: To perform a three-country comparison, the authors selected a morphologically diverse set of 188 conventional Papanicolaou tests initially classified as "squamous atypia" from a study of more than 20,000 women in Portland, Oregon (1989-1990). Previously, five U.S. expert cytopathologists independently interpreted the slides with screening cytotechnologists' marks in place. For this comparison, one British and two Scandinavian reviewers involved in HPV research reviewed the slides after original marks had been removed. The authors compared all eight reviewers' classifications of negative, equivocal, or abnormal in a series of pairwise comparisons using the kappa statistic. They then compared cytologic interpretations with HPV DNA testing. RESULTS: Oncogenic HPV DNA detection was significantly associated with increasingly abnormal interpretations for each reader. The British reader tended to rate tests as more abnormal than the American pathologists did, whereas the Scandinavians tended to rate tests as more normal. Reference to the HPV DNA standard clarified the tendency of readers to render systematically more or less severe interpretations. For example, the Scandinavian cytologists discounted subtle (often HPV-associated) changes in favor of cytologic certainty, making HPV triage of equivocal tests less applicable there. CONCLUSIONS: International research on cytopathology, particularly on the possible uses of HPV DNA testing, will require calibration of local cytologic definitions.

Adolescent↗

PubMed2002

Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS).

BACKGROUND: Testing for oncogenic human papillomavirus (HPV) DNA at a 1.0-pg/mL threshold represents a promising approach for colposcopy triage of atypical squamous cells of undetermined significance (ASCUS), but not for low-grade squamous intraepithelial lesions (LSIL). Considering age or viral load could improve colposcopy triage. METHODS: We determined the sensitivity for detecting Cervical Intraepithelial Neoplasia 3 (CIN3) and cancer and the percentage of referrals for colposcopy using HPV testing and repeat thin-layer cytopathology in 2198 women with ASCUS and in 848 women with LSIL enrolled in ALTS from November 1996 through December 1998. We analyzed results by age and at two thresholds for HPV load and repeat cytopathology. RESULTS: For ASCUS, the overall sensitivity of HPV testing at 1.0 pg/mL was 96.1% (95% confidence interval [CI] = 92.8 to 99.5%) and varied minimally with age (range, 93.9% to 97.8%). HPV testing at this threshold would refer 31.2% (95% CI = 28.0% to 34.3%) of women aged 29 years or older as compared with more than 65% of younger women. Among women aged 29 years or older with ASCUS, referral for repeat cytopathology of ASCUS had a sensitivity of 90.9% (95% CI = 81.1% to 100.0%) and would refer 50.1% (95% CI = 46.7 to 53.5%). Among all ASCUS, HPV testing using a 10.0-pg/mL threshold decreased sensitivity to 91.5% and referrals to 41.7%. More than 63% of LSIL would have been referred using any strategy achieving 90% sensitivity. CONCLUSION: For women with ASCUS, HPV testing was highly sensitive for detecting CIN3 and cancer with dramatically fewer referrals of older women. Neither a single HPV test nor repeat cytopathology provides useful triage for women with LSIL.

Adult↗

PubMed2002

Comparisons of HPV DNA detection by MY09/11 PCR methods.

Two modifications to the original L1 consensus primer human papillomavirus (HPV) PCR method, MY09-MY011, using AmpliTaq DNA polymerase (MY-Taq), were evaluated for HPV DNA detection on clinical specimens from a cohort study of cervical cancer in Costa Rica. First, HPV DNA testing of 2978 clinical specimens by MY09-MY011 primer set, using AmpliTaq Gold DNA polymerase (MY-Gold) were compared with MY-Taq testing. There was 86.8% total agreement (kappa = 0.72, 95%CI = 0.70-75) and 69.6% agreement among positives between MY-Gold and MY-Taq. MY-Gold detected 38% more HPV infections (P < 0.0001) and 45% more cancer-associated (high-risk) HPV types (P < 0.0001) than MY-Taq, including 12 of the 13 high-risk HPV types. Analyses of discordant results using cytologic diagnoses and detection of HPV DNA by the Hybrid Capture 2 Test suggested that MY-Gold preferentially detected DNA positive specimens with lower HPV viral loads compared with MY-Taq. In a separate analysis, PGMY09-PGMY11 (PGMY-Gold), a redesigned MY09/11 primer set, was compared with MY-Gold for HPV DNA detection (n = 439). There was very good agreement between the two methods (kappa = 0.83; 95%CI = 0.77-0.88) and surprisingly no significant differences in HPV detection (P = 0.41). In conclusion, we found MY-Gold to be a more sensitive assay for the detection of HPV DNA than MY-Taq. Our data also suggest that studies reporting HPV DNA detection by PCR need to report the type of polymerase used, as well as other assay specifics, and underscore the need for worldwide standards of testing.

Cervix Uteri↗

PubMed2002

Can cervicography be improved? An evaluation with arbitrated cervicography interpretations.

OBJECTIVE: The purpose of this study was to estimate the optimal performance of cervicography. We compared an arbitrated cervigram classification with an arbitrated referent diagnosis of cervical neoplasia. STUDY DESIGN: From an initial group of 8460 women, a stratified sample of cervigrams from 3645 women and histologic information from 414 women underwent arbitration. Interobserver agreement was assessed for cervicography and the referent diagnosis. Sensitivity, specificity, and predictive values were estimated for initial and arbitrated cervicography results, compared with the initial and arbitrated referent diagnoses. RESULTS: For the detection of arbitrated high-grade lesions or cancer, arbitrated cervicography yielded an overall sensitivity of 63.9% and a specificity of 93.7%. Significantly higher sensitivity was associated with younger age and age-related visual characteristics. CONCLUSION: Optimization of the cervigram classification improved performance over a single interpretation in this population but suggested the limits of static visual screening.

Colposcopy↗

PubMed2002

Hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas.

Determining the origin of uterine adenocarcinomas can be difficult in biopsy and curettage specimens because the morphologic spectrum of endocervical and endometrial adenocarcinomas overlaps. In addition, in hysterectomy specimens the primary site is often equivocal for tumors that involve predominantly the lower uterine segment and endocervix and lack identifiable precursor lesions. We assessed the value of immunohistochemistry for estrogen and progesterone receptors and in situ hybridization for human papillomavirus DNA detection in making this clinically relevant distinction. We evaluated a set of 48 adenocarcinomas of unequivocal origin (24 endocervical carcinomas and 24 endometrial endometrioid carcinomas without cervical extension) and then tested seven lower uterine segment/endocervical carcinomas of equivocal origin to determine whether patterns established in the initial set would permit definitive assignment of primary site for the equivocal set. Only one (4.2%) of 24 endocervical carcinomas was positive for both estrogen receptor and progesterone receptor, whereas 18 (75%) of 24 endometrial carcinomas were positive for estrogen receptor and 23 (95.8%) of 24 endometrial carcinomas were positive for progesterone receptor (p <0.001, chi2 test). Human papillomavirus DNA was detected in 16 (66.7%) of 24 endocervical carcinomas and in none of 24 endometrial carcinomas (p <0.001, chi2 test). Of the seven tumors of equivocal origin, five could be definitively classified as either endocervical or endometrial in origin based on their demonstration of a characteristic profile with these assays (either estrogen receptor/progesterone receptor-negative/human papillomavirus-positive, consistent with endocervical origin or estrogen receptor/progesterone receptor-positive/human papillomavirus-negative, consistent with endometrial origin). We conclude that hormone receptor immunohistochemistry and human papillomavirus in situ hybridization are useful for distinguishing endocervical and endometrial adenocarcinomas. The clinical utility of these techniques should be evaluated in studies that include curettage and biopsy specimens.

Adenocarcinoma↗

PubMed2002

Salpingitis, salpingoliths, and serous tumors of the ovaries: is there a connection?

We have observed luminal and mucosal calcifications frequently surrounded by a mantle of bland epithelium in the fallopian tubes ("salpingoliths") of women with serous tumors of the ovaries. These lesions resemble noninvasive peritoneal "implants" in women with advanced stage atypical proliferative serous tumors (APSTs) and micropapillary serous carcinomas (MPSCs). The presence of salpingitis and salpingoliths was prospectively evaluated in 358 women with a variety of nonneoplastic and neoplastic ovarian conditions and compared with 87 previously reported women with APSTs/MPSCs in an effort to determine whether these lesions were specifically associated with serous tumors. The frequency of chronic salpingitis among women without ovarian pathology was 27%, and the frequency of salpingoliths was 4%. Serous epithelial tumors (cystadenomas, APST/MPSC, and carcinomas) were significantly more often associated with chronic salpingitis (53%) and salpingoliths (32%) than all other cases with or without ovarian neoplasms (p<0.01). APSTs/MPSCs were associated with salpingoliths significantly more frequently than all other groups (p<0.001). For patients with APSTs/MPSCs, salpingoliths were found significantly more often in advanced stage (FIGO II and III) patients (51%) than stage I patients (24%) (p<0.01), but salpingitis, present in 60% of these patients, was not stage-dependent (p>0.05). Chronic salpingitis was identified in 66% of women with endometriosis, which was significantly more frequent than those with normal ovaries (27%) (p<0.001). In conclusion, fallopian tube abnormalities may be related to both the high frequency of infertility and the noninvasive peritoneal implants in women with APSTs/MPSCs. Whether the fallopian tubes with salpingoliths are the source of the peritoneal "implants," the recipient of implants, or are independent is unknown. In addition, the high frequency of salpingitis in women with endometriosis may be related to the mechanism of endometriosis-associated infertility.

Calcinosis↗

PubMed2002

Sexual behavior, human papillomavirus type 16 (HPV 16) infection, and HPV 16 seropositivity.

BACKGROUND: Sexual behaviors have been linked to seropositivity for human papillomavirus (HPV) but not with the magnitude of the seroreactivity. GOALS: The objective of this analysis was to examine the association of sexual behavior, cervical HPV 16 DNA positivity at enrollment (past) and at diagnosis (current), and other potential determinants with the likelihood and magnitude of HPV 16 seropositivity at diagnosis. STUDY DESIGN: With use of stored specimens from an incidence case-control study at Kaiser Permanente (Portland, OR), women were tested for seroreactivity to HPV 16 by enzyme-linked immunosorbent assay with virus-like particles at diagnosis and were tested for past and concurrent cervical HPV 16 DNA positivity with MY09/MY11 L1 consensus primer PCR. Questionnaire data were used to ascertain past sexual behavior. RESULTS: Increased lifetime number of sex partners (P(Trend) < 0.001), past HPV 16 DNA positivity (odds ratio = 6.9; 95% confidence interval = 1.5-31), and a current cytologic diagnosis (P(Trend) < 0.03) were independently associated with HPV 16 seropositivity. Among the seropositive, only lifetime number of sex partners (P(Trend) < 0.001) and past HPV 16 DNA positivity (P = 0.003) were independently associated with mean signal strength (optical density) in an age-adjusted analysis. Women negative for past and concurrent HPV 16 DNA had a significant trend of increasing optical densities associated with greater numbers of lifetime partners (P(Trend) < 0.001). Conversely, the mean signal strength for those women who were ever HPV 16 DNA-positive during the study did not depend on lifetime numbers of sex partners (P(Trend) = 0.36). CONCLUSIONS: HPV 16 seropositivity is a surrogate for past HPV 16 infection. Circulating levels of antibodies to HPV 16 may reflect recent HPV 16 infection or the frequency of past HPV 16 infection.

Adult↗

PubMed2002

Results of human papillomavirus DNA testing with the hybrid capture 2 assay are reproducible.

Reproducibility of the Hybrid Capture 2 Test (HC 2) for human papillomavirus (HPV) DNA detection was evaluated by assaying frozen cervical specimens in 1997 and again in 2001 from 1,775 women with normal cervical cytology. Using a cutoff point of 1.0 pg of HPV DNA/ml between a negative and a positive test result, the result of the kappa test for agreement was 0.72 (a kappa value of >0.60 is considered good agreement). Using cutoff points of 1.0 and 10.0 pg/ml between negative and low positive and between low positive and high positive, respectively, the kappa was 0.68 and the linear-weighted kappa was 0.76. The results of this study indicate that HC 2 testing is reproducible even among cytologically normal women with low test values.

Cervix Uteri↗