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L Stewart Massad

Publications and source records attributed to L Stewart Massad.

At least 19 recordsLinked to original sources

Cervical cancer prevention in the era of prophylactic vaccines: a preview for gynecologic oncologists.

OBJECTIVE: The recent approval of a vaccine to prevent HPV infection is an important advance in cervical cancer prevention. This article is intended to provide gynecologic oncologists with a comprehensive background in modern cervical cancer prevention strategies. METHODS: We describe and contrast the quadrivalent and bivalent vaccines. More established cervical cancer prevention strategies are reviewed, with comments on the impact of HPV vaccination. Clinical guidance is provided for use of the approved quadrivalent vaccine. Safety and side effects of both vaccines are reviewed and future questions and challenges are explored. RESULTS: It is vitally important that both vaccinated and unvaccinated women continue to fully engage in cervical cancer prevention, including cervical cancer screening, follow-up of abnormal screens, and treatment of premalignant lesions. A quadrivalent virus-like particle vaccine has now been approved for use in girls and women ages 9 to 26. A bivalent vaccine may be available soon. Vaccine efficacy in clinical trials has been outstanding, with 100% protection against HPV-type-specific cervical intraepithelial neoplasia (CIN) II and III. CONCLUSIONS: Comprehensive cervical cancer protection now includes prophylactic vaccination for girls and young women in addition to screening and treatment of premalignant changes. Gynecologic oncologists will continue to play an important role in promoting optimal prevention practices.

Adolescent↗

Effects of HIV infection and its treatment on self-reported menstrual abnormalities in women.

OBJECTIVE: To describe menstrual abnormalities among women with HIV. METHODS: Women in a multicenter prospective cohort study of HIV natural history reported menstrual abnormalities every 6-months between October 1994 and September 2002. Logistic regression and Cox proportional-hazards models were applied. RESULTS: The prevalence and incidence of menstrual abnormalities were <20%. HIV serostatus was not associated with prevalent menstrual abnormalities, but in HIV-seropositive women, higher CD4 counts were associated with fewer problems: compared with women with CD4 counts <200/mm3, in women with counts 200-500/mm3, odds ratio (OR) for amenorrhea was 0.55, p = 0.02, and for oligomenorrhea was 0.54, p = 0.0003; for women with counts >500/mm3, OR for amenorrhea was 0.67, p = 0.14, and for oligomenorrhea was 0.55, p = 0.001. HIV serostatus was not associated with incident abnormalities. Highly active anti-retroviral therapy (HAART) use was not associated with prevalent abnormalities, but both HAART use and higher CD4 counts were linked to lower rates of incident menstrual problems. CONCLUSIONS: Compared with seronegative women, HIV-seropositive women are at increased risk for some menstrual changes, although the absolute frequency of most abnormalities is low. Higher CD4 counts and HAART protect against incident abnormalities.

Adult↗

Effects of human immunodeficiency virus on protracted amenorrhea and ovarian dysfunction.

OBJECTIVE: To characterize ovarian failure and prolonged amenorrhea from other causes in women who are both human immunodeficiency virus (HIV) seropositive and seronegative. METHODS: This was a cohort study nested in the Women's Interagency HIV Study, a multicenter U.S. study of HIV infection in women. Prolonged amenorrhea was defined as no vaginal bleeding for at least 1 year. A serum follicle stimulating hormone more than 25 milli-International Units/mL and prolonged amenorrhea were used to define ovarian failure. Logistic regressions, chi2, and t tests were performed to estimate relationships between HIV-infection and cofactors with both ovarian failure and amenorrhea from other causes. RESULTS: Results were available for 1,431 women (1,139 HIV seropositive and 292 seronegative). More than one half of the HIV positive women with prolonged amenorrhea of at least 1 year did not have ovarian failure. When adjusted for age, HIV seropositive women were about three times more likely than seronegative women to have prolonged amenorrhea without ovarian failure. Body mass index, serum albumin, and parity were all negatively associated with ovarian failure in HIV seropositive women. CONCLUSION: HIV serostatus is associated with prolonged amenorrhea. It is difficult to ascertain whether the cause of prolonged amenorrhea is ovarian in HIV-infected women without additional testing. LEVEL OF EVIDENCE: II-2.

Adolescent↗

Home Study Course: Winter 2006.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1 hour Category I credit of the ASCCP's Program for Continuing Professional Development and the Physician's Recognition Award of the American Medical Association. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements. DISCLOSURE: Faculty must disclose any significant financial interest or relationship with proprietary entities that may have a direct relationship to the subject matter. For this course, the author had no such relationship to report.

Adolescent↗

Knowledge of the cervical cancer screening process among rural and urban illinois women undergoing colposcopy.

OBJECTIVE: To describe knowledge of the cervical cancer prevention process among rural and urban women referred for evaluation of abnormal cytology. MATERIALS AND METHODS: Women with abnormal screening cervical cytology attending university colposcopy clinics (n = 178) were asked about demographic factors and knowledge of Pap testing, human papillomavirus (HPV) infection, and risk factors for cervical cancer. Responses were tabulated, and correlations assessed. RESULTS: Only 131 (74%) of 176 responding women understood that Pap tests evaluate the cervix, whereas 137 (78%) understood that Pap tests should be repeated at intervals of 1-3 years. The cancer screening function of a Pap test was identified by 122/177 (69%), but only 99 (56%) knew HPV is sexually transmitted and causes warts and premalignant changes. Rural residence was not associated with knowledge, but older women were more likely to know the nature of the Pap test (p =.005) and the meaning of an abnormal Pap test (p = .04). Women in higher income strata were more likely to understand the meaning of an abnormal Pap test (p = .03), the nature of HPV (p = .005), and risk factors for cervical cancer (p = .03). College graduates were better (p = .0005), and women of greater parity were less (p = .02) able than others to identify the nature of HPV, although neither differed from others in ability to answer other questions correctly (p > .1). CONCLUSIONS: Income and education are better predictors of knowledge of the cervical cancer prevention process than rural residence. Higher rates of cervical cancer in rural areas may reflect lower educational attainment and lower income.

Adult↗

Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women.

BACKGROUND: Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD4+ T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation--whether it occurs and with what frequency in HIV-positive women. METHODS: HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided. RESULTS: We observed a strong interaction between the associations of CD4+ and plasma HIV RNA strata with both prevalent (P(interaction) = .002) and incident (P(interaction) = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4+ count of less than 200 cells per mm3 or an HIV RNA level of more than 100,000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners (P(trend)<.001), 22% of sexually inactive HIV-positive women with a CD4+ count of less than 200 cells/mm3 also had at least one incidentally detected HPV type. The association between CD4+/HIV RNA strata and HPV persistence was statistically significantly smaller (P<.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4+/HIV RNA strata as HPV (above). CONCLUSION: In HIV-positive women, plasma HIV RNA level and CD4+ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.

AIDS-Related Opportunistic Infections↗

Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results.

CONTEXT: Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. OBJECTIVE: To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. DESIGN, SETTING, AND PATIENTS: Participants were HIV-seropositive (n = 855; mean age, 36 years) and HIV-seronegative (n = 343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. MAIN OUTCOME MEASURE: The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. RESULTS: Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/microL, 9% (95% CI, 1%-18%); with CD4 counts between 200/muL and 500/microL, 9% (95% CI, 4%-13%); and with CD4 counts greater than 500/microL, 4% (95% CI, 1%-7%). The CIs for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% CI, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/microL (hazard ratio [HR], 1.2; 95% CI, 0.5-3.0), but not those with CD4 counts less than or equal to 500/microL (HR, 2.9; 95% CI, 1.2-7.1), was similar to that in HIV-seronegative women. CONCLUSION: The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/microL and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial.

Adult↗

Quantifying the risk of cervical intraepithelial neoplasia in women with unsatisfactory colposcopy results.

OBJECTIVE: To define the risk of high-grade cervical intraepithelial neoplasia (CIN 2,3) among women with unsatisfactory colposcopy results who underwent a loop electrosurgical excision procedure. METHODS: Loop electrosurgical excision procedures were performed for clinical indications by residents supervised by attending obstetrician-gynecologists at an urban public hospital referral clinic. Specimens obtained between July 1, 1996, and April 30, 2002, were retrieved retrospectively after grading and recording in an institutional database. The endpoint of interest was high-grade cervical disease, a composite of CIN 2, CIN 3, and cancer, in excision specimens. RESULTS: Of 169 evaluable patients, five (3%) had cancer. High-grade disease was found in 6 of 21 patients (29%) without a colposcopic lesion, in 13 of 33 patients (36%) with only koilocytosis on colposcopic biopsy, in 15 of 55 patients (27%) with CIN 1, in 13 of 25 patients (54%) with CIN 2, and in 26 of 35 patients (74%) with CIN 3 (p < 0.001). High-grade disease was associated with the grade of referral cytologic results, cytologic analysis repeated at colposcopy, and colposcopic biopsy (p < 0.001 for all). Limiting excision to women with cytologic results at the time of colposcopy read as atypical squamous cells of undetermined significance or worse yielded a high-grade disease prevalence of 12%, with a sensitivity of 92%, specificity 46%, negative predictive value 88%, and positive predictive value 56%. Referral cytologic results, colposcopic biopsy, age, and endocervical curettage results did not seem to identify women at low risk for high-grade disease. CONCLUSIONS: Women with negative cytologic results at the time of colposcopy have a low risk for high-grade disease and may avoid a loop electrosurgical excision procedure despite unsatisfactory colposcopy.

Adult↗

Outcome after negative colposcopy among human immunodeficiency virus-infected women with borderline cytologic abnormalities.

OBJECTIVE: To estimate the risk of and risk factors for progression among human immunodeficiency virus (HIV)-seropositive women with abnormal cervical cytology but negative colposcopy. METHODS: In a prospective cohort study, 391 HIV-seropositive and 103 seronegative women with cervical cytology read as atypical squamous cells (ASC) or low-grade squamous intraepithelial lesion (LSIL) but negative colposcopy were followed up for a mean of 4.0 years with cytology at 6-month intervals. Colposcopy was prescribed for any epithelial abnormality. RESULTS: Progression to CIN2, CIN3, high-grade SIL/severe dysplasia, or cancer occurred in 47 (12%) HIV-seropositive women and 4 (4%) HIV-seronegative women (P = .02). Progression to CIN1 was seen in an additional 12 HIV-seropositive women and 1 seronegative woman. In multivariate analysis, high-risk but not low-risk HPV detection (hazard ratio [HR] 2.46-95% confidence interval [CI] 1.18-5.12, P = .02 for high risk, HR 1.41, 95% CI 0.62-3.21, P = .42 for low risk), satisfactory colposcopy (HR 2.01, 95% CI 1.11-3.65, P = .02), and non-Hispanic African-American ethnicity (HR 5.08, 95% CI 1.72-14.98, P = .003) were the only factors associated with progression, while HIV serostatus was marginally significant (HR 2.53, 95% CI 0.85-7.50, P = .09). CONCLUSION: Human immunodeficiency virus-seropositive women with negative colposcopy after borderline cytology face a higher risk of progression than seronegative women, but the absolute risk is low and becomes nonsignificant after controlling for HPV risk type, ethnicity, and colposcopic findings. Observation is appropriate. LEVEL OF EVIDENCE: II-2.

Adult↗

Variants of human papillomaviruses 16 and 18 and their natural history in human immunodeficiency virus-positive women.

Highly oncogenic human papillomavirus (HPV) 16 and 18 variants might be expected to be particularly aggressive in HIV-positive women. The association of HPV16 and 18 variant lineages with race, human immunodeficiency virus (HIV) coinfection, CD4+ T-cell count, HIV-RNA level, time-to-clearance of HPV infection and presence of squamous intraepithelial lesions (SIL) among women in the Women's Interagency HIV Study was studied. Subjects were followed semi-annually with Pap smear and cervicovaginal lavage (CVL). HPV DNA was detected in CVLs using MY09/11 L1 PCR assay. Specimens positive for HPV16/18 underwent E6 PCR and sequencing to determine the variant present. Specimens from 195 HPV16- and 162 HPV18-positive women were classified into variant lineages based on sequencing results. African variants of HPV16 and HPV18 were significantly more prevalent among African-Americans than among Caucasians [42 versus 14 % (P=0.001) and 60 versus 13 % (P<0.001), respectively]. However, it was not possible to detect associations between the HPV16 or 18 variant lineages and other factors studied. African variants of HPV16/18 were more common in women of African descent living outside Africa, which could reflect mixing behaviours and/or immunogenetic factors. However, in a large population of HIV-infected women, the variant of HPV16 or 18 was unrelated to persistence of infection or presence of SIL. If non-European variants are more oncogenic, the effect may involve a late stage in cervical tumorigenesis.

AIDS-Related Opportunistic Infections↗

Cancer risk among participants in the women's interagency HIV study.

BACKGROUND: The HIV epidemic has been associated with an increased incidence of specific cancers. However, less is known about cancers occurring in HIV-infected women than men. METHODS: To determine the risk of cancer among HIV-infected and at-risk HIV-uninfected women, cancer incidence data from the Women's Interagency HIV Study (WIHS) were compared with data from the population-based United States Surveillance, Epidemiology, and End Results (SEER) registry. Age- and race-adjusted standardized incidence ratios (SIRs) were computed and exact statistical tests were used to measure significance. RESULTS: Among the 1950 women participants (1554 HIV infected, 391 HIV uninfected, and 5 HIV seroconverters), 48 cancers were diagnosed during study follow-up. Among HIV-infected women, significantly (P < 0.05) increased incidence rates were observed for all cancer types (SIR = 1.9), Kaposi sarcoma (SIR = 213.5), non-Hodgkin lymphoma (NHL) (SIR = 19.0), and lung cancer (SIR = 6.3) when compared with SEER rates. Lung cancer incidence was also elevated (P = 0.07) among the HIV-uninfected women (SIR = 6.9), when compared with SEER rates, and was similar to the SIR for HIV-infected women. While the incidence rate of NHL among HIV-infected women was significantly lower during the era of highly active antiretroviral therapy (HAART) compared with the pre-HAART era (relative risk = 0.15, P = 0.005), the incidence of NHL among HIV-infected WIHS participants remained significantly higher than in the US population (SIR = 6.4, 95% CI = 1.3-15.5). CONCLUSION: In the HAART era, the higher rates of cancer among HIV-infected women, coupled with increased life expectancy, should lead to more intensive cancer screening and prevention efforts in this population.

Adult↗

Highly active antiretroviral therapy and cervical squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: Women infected with human immunodeficiency virus (HIV) have an increased risk of persistent squamous intraepithelial lesions (SILs) of the cervix. We assessed the association between use of highly active antiretroviral therapy (HAART) and regression of SIL in HIV-infected women enrolled in the Women's Interagency HIV Study, a large, multicenter, prospective cohort study. METHODS: Of 2059 HIV-infected participants, 312 HIV-infected women had normal cervical cytology at baseline and were subsequently diagnosed during 7 years of follow-up with incident SIL. Pap smears, CD4+ T-cell counts, and information regarding use of HAART were obtained every 6 months. The outcome of interest was lesion regression, defined as two consecutive normal Pap smears 6 months apart. Incidence rates of SIL regression were computed among person-years at risk, both before and after HAART initiation. All statistical tests were two-sided. RESULTS: Of 312 women, 141 had lesions that regressed to normal cytology, with a median time to regression of 2.7 years. Overall, the incidence of regression increased (P(trend) =.002) over time after HAART was introduced. At incident SIL, median CD4+ T-cell counts were lower in women whose lesions did not regress than in women whose lesions regressed (230 versus 336 cells/microL; P<.01). Before HAART was introduced, the rate of lesion regression was 0.0% (95% confidence interval [CI' = 0.0% to 2.4%). After HAART was introduced, the rate was 12.5% (95% CI = 9.9% to 15.1%) and was related to post-HAART CD4+ T-cell counts (P(trend) =.002). CONCLUSIONS: HAART use was associated with increased regression of SIL among HIV-infected women, and among women who used HAART, increased CD4+ T-cell counts were associated with a greater likelihood of regression. However, the majority of cervical lesions among HIV-infected women, even among individuals who used HAART, did not regress to normal.

AIDS-Related Opportunistic Infections↗

Pregnancy rates and predictors of conception, miscarriage and abortion in US women with HIV.

OBJECTIVE: To determine frequency and outcomes of pregnancy in US women with HIV before and after introduction of highly active antiretroviral therapy (HAART). DESIGN: Prospective cohort study at six US centers. METHODS: HIV seropositive and at-risk seronegative women reported pregnancy outcomes at 6-month intervals during the period 1 October 1994 to 31 March 2002. Outcomes were tabulated and pregnancy rates calculated. Logistic regression defined outcome correlates. RESULTS: Pregnancy rates were 7.4 and 15.2 per 100 person-years in seropositive and seronegative women, respectively (P < 0.0001). Among seropositives, 119 (36%) pregnancies ended in live birth, six (2%) in stillbirth, 126 (36%) in abortion, 83 (24%) in miscarriage, 16 (5%) in ectopic pregnancy, and two (1%) in other outcomes (P = nonsignificant versus seronegatives). Independent baseline correlates of conception in seropositives included younger age [odds ratio (OR), 1.20; 95% confidence interval (CI), 1.16-1.23], prior abortion (OR, 1.79; 95% CI, 1.25-2.63), lower HIV RNA levels (OR, 1.30; 95% CI, 1.10-1.54 for each log decrease), and being unmarried (OR, 1.59; 95% CI, 1.02-2.44). Baseline antiretroviral use at baseline was linked to lower conception risk (OR, 0.34; 95% CI, 0.49-0.98 for mono- or combination therapy; OR, 0.34; 95% CI, 0.03-4.28 for HAART). Abortion was less likely during the HAART era, (OR, 0.68; 95% CI, 0.35-1.33 during the early HAART era; OR, 0.46; 95% CI, 0.23-0.90 during the later HAART era, compared with before HAART). CONCLUSIONS: Women with HIV were less likely to conceive than at-risk uninfected women, but pregnancy outcomes were similar. Abortion became less common after the introduction of HAART.

Abortion, Induced↗

Low incidence of invasive cervical cancer among HIV-infected US women in a prevention program.

OBJECTIVE: To measure the incidence of invasive cervical cancer (ICC) in US women infected with HIV. DESIGN: Multicenter prospective cohort study, conducted between October 1994, and September 2001. SETTING: HIV research centers operating as six urban consortia in the Women's Interagency HIV Study. SUBJECTS: A total of 2131 women (462 HIV seronegative, 1661 HIV seropositive, and eight seroconverters). Women with a history of hysterectomy or of cervical cancer at baseline evaluation were excluded. INTERVENTION: Cervical cytology obtained at 6-month intervals, with a colposcopy referral threshold of atypia, followed by individualized treatment. MAIN OUTCOME MEASURE: ICC diagnoses obtained from study databases and regional cancer registries and confirmed by a gynecologic pathologist. RESULTS: No incident ICC were observed in HIV seronegative women during 2375 woman-years of observation. During 8260 woman-years of observation, eight putative incident cases of cervical cancer were identified in HIV seropositive women, but only one was confirmed, yielding an incidence rate of 1.2/10 000 woman-years (95% confidence interval, 0.3-6.7/10 000 woman-years). The difference in incidence between HIV seropositive and seronegative women was not significant (P = 1.0). CONCLUSION: ICC is uncommon in HIV-infected US women participating in a regular prevention program.

Adult↗