Cancer Epidemiology and Prevention Biomarkers, 2007
A106 Objective : Although Hispanics represent the fasting growing population in the United States... more A106 Objective : Although Hispanics represent the fasting growing population in the United States, there is limited data on the prevalence of abnormal cervical cytology in this group. We evaluated the prevalence of abnormal cervical cytology in Hispanic women screened in a health fair setting. Materials and Methods : A retrospective chart review of all women presenting for health care screening at the Atlanta Grady Health System (GHS) sponsored Dia de la Mujer Latina (DML) health fair in 2005 and 2006 was performed. Women underwent a full physical exam and, where appropriate, liquid based cervical cytology screening. The results from the fair were compared to an outpatient clinic population of similar socio-economic status seen at the GHS during the first fiscal quarter. Patient’s within the GHS were further stratified to low-risk (LR; patients presenting to primary care clinics) or high-risk (HR; patients referred to the hospital-based gynecology clinic for a specified problem) gr...
Objective The aim of the study was to elucidate the risk factors underlying abnormal cytology-bas... more Objective The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. Methods Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. Results Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely...
Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic ac... more Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic activities of mouse kidney where the proximal tubule and Bowman's capsule from the same corpuscle were viewed in the same section. Alkaline phosphatase, acid phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, N-acetyl-beta-glucosaminidase, leucine aminopeptidase, alpha-naphthyl butyrate esterase, and adenosine triphosphatase activities were observed in the proximal tubule, but only 5'-nucleotidase, alpha-naphthyl butyrate esterase, and alkaline phosphatase were observed in the squamous portion of the parietal epithelium of Bowman's capsule. The use of methacrylate-embedded tissue allowed more precise localization of enzymatic activity than is possible with most frozen sections. This may provide interesting applications not only for characterization of kidney diseases but also for characterization of other normal and abnormal tissues.
While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alo... more While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.
Cancer Epidemiology, Biomarkers & Prevention, 2007
Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but the... more Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (Ct) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67...
The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development ... more The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined. Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (O) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an alpha level of 0.05. Among cervical cancer index cases, there was a significant elevated risk for subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2). The results of the current study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident.
Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) ... more Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that f35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the ratelimiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples. Increased aromatase was associated with increases in estrogen receptors (ER-A and ER-B) and a decrease in progesterone receptor levels, suggesting that in situ estrogen signaling via ER may be involved in tumor growth. Stable overexpression of aromatase in HPV cervical cancer cells resulted in increased cellular proliferation, anchorage-independent growth, and ER expression and activity. In contrast...
Gay, bisexual, and other men who have sex with men (MSM) experience disproportionately high burde... more Gay, bisexual, and other men who have sex with men (MSM) experience disproportionately high burdens of Human Papilloma Virus (HPV)-associated anal cancers. Recent focus has shifted to anorectal cancer prevention through high-resolution anoscopy (HRA); however, little is known about sexual minority men’s perceptions, attitudes, or beliefs regarding HRA. We conducted 4 qualitative Focus Group Discussions (FGDs) (n = 15) with sexual minority men, focusing on their beliefs, attitudes, and perceptions of undergoing HRA. Participants discussed their experiences of HPV/HRA as influenced by both their gender and sexuality, including unawareness of HPV disease as a male health issue, challenges relating to female-oriented HPV/HRA language, conception of HPV/HRA as related to prostate health, and connecting their sexual behavior identification as “bottoms” to their need for HRA. As efforts to improve HRA knowledge, access, and uptake among sexual and gender minority communities increase, spec...
A86 Background: Women diagnosed with cervical cancer tend to have specific risk factors for devel... more A86 Background: Women diagnosed with cervical cancer tend to have specific risk factors for developing a cancer later in life: infection with the Human Papillomavirus (HPV), history of smoking, and/or treatment with radiation therapy. Recent licensure of an HPV vaccine protecting against HPV 16 and 18 has raised the issue of whether current racial/ethnic disparities in cervical cancer will improve or worsen. Since the HPV vaccine has the ability to impact more than one HPV-related cancer in the same individual, we examine whether there are racial/ethnic differences in developing subsequent primary cancers (invasive and in situ) after an initial invasive cervical cancer diagnosis. Methods: Using the SEER 13 Cancer Registry data (1992-2004), we identified 23,059 women with invasive cervical cancer and observed subsequent malignancies (including some in situ) in that cohort during 4.75 mean person-years of follow-up. We focused on HPV-associated cancers (vaginal, vulvar, anal, rectal,...
Objective The aim of the study was to describe the incidence and correlates of atypical glandular... more Objective The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. Materials and Methods Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. Results Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. Conclusions This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.
IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point ... more IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and C...
ABSTRACT The American Cancer Society (ACS) released updated cervical cancer screening guidelines ... more ABSTRACT The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.
Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomav... more Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods We enrolled n = 865 WLWH (323 from the Women’s Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[−]/Pap[−] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histo...
Cancer Epidemiology and Prevention Biomarkers, 2007
A106 Objective : Although Hispanics represent the fasting growing population in the United States... more A106 Objective : Although Hispanics represent the fasting growing population in the United States, there is limited data on the prevalence of abnormal cervical cytology in this group. We evaluated the prevalence of abnormal cervical cytology in Hispanic women screened in a health fair setting. Materials and Methods : A retrospective chart review of all women presenting for health care screening at the Atlanta Grady Health System (GHS) sponsored Dia de la Mujer Latina (DML) health fair in 2005 and 2006 was performed. Women underwent a full physical exam and, where appropriate, liquid based cervical cytology screening. The results from the fair were compared to an outpatient clinic population of similar socio-economic status seen at the GHS during the first fiscal quarter. Patient’s within the GHS were further stratified to low-risk (LR; patients presenting to primary care clinics) or high-risk (HR; patients referred to the hospital-based gynecology clinic for a specified problem) gr...
Objective The aim of the study was to elucidate the risk factors underlying abnormal cytology-bas... more Objective The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. Methods Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. Results Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely...
Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic ac... more Two-micrometer sections of methacrylate-embedded kidney were used to investigate the enzymatic activities of mouse kidney where the proximal tubule and Bowman's capsule from the same corpuscle were viewed in the same section. Alkaline phosphatase, acid phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, N-acetyl-beta-glucosaminidase, leucine aminopeptidase, alpha-naphthyl butyrate esterase, and adenosine triphosphatase activities were observed in the proximal tubule, but only 5'-nucleotidase, alpha-naphthyl butyrate esterase, and alkaline phosphatase were observed in the squamous portion of the parietal epithelium of Bowman's capsule. The use of methacrylate-embedded tissue allowed more precise localization of enzymatic activity than is possible with most frozen sections. This may provide interesting applications not only for characterization of kidney diseases but also for characterization of other normal and abnormal tissues.
While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alo... more While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.
Cancer Epidemiology, Biomarkers & Prevention, 2007
Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but the... more Numerous molecular biomarkers have been suggested for early detection of cervical cancer, but their usefulness in routinely collected exfoliated cells remains uncertain. We used quantitative reverse transcription-PCR to evaluate expression of 40 candidate genes as markers for high-grade cervical intraepithelial neoplasia (CIN) in exfoliated cervical cells collected at the time of colposcopy. Samples from the 93 women with CIN3 or cancer were compared with those from 186 women without disease matched (1:2) for age, race, and high-risk human papillomavirus status. Normalized threshold cycles (Ct) for each gene were analyzed by receiver operating characteristics to determine their diagnostic performance in a split sample validation approach. Six markers were confirmed by an area under the curve >0.6 in both sample sets: claudin 1 (0.75), minichromosome maintenance deficient 5 (0.71) and 7 (0.64), cell division cycle 6 homologue (0.71), antigen identified by monoclonal antibody Ki-67...
The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development ... more The recent licensure of human papillomavirus (HPV) vaccines will likely decrease the development of primary in situ and invasive cervical cancers and possibly other HPV-associated cancers such as vaginal, vulvar, and anal cancers. Because the HPV vaccine has the ability to impact the development of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 HPV-associated cancer in the same individual, the risk of developing subsequent primary cancers among cervical cancer survivors was examined. Using the 1992 through 2004 data from the Surveillance, Epidemiology, and End Results (SEER) program, 23,509 cervical cancer survivors were followed (mean of 4.8 person-years) for the development of subsequent primary cancers. The observed number (O) of subsequent cancers of all sites were compared with those expected (E) based on age-/race-/year-/site-specific rates in the SEER population. Standardized incidence ratios (SIRs = O/E) were considered statistically significant if they differed from 1, with an alpha level of 0.05. Among cervical cancer index cases, there was a significant elevated risk for subsequent in situ cancers of the vagina and vulva (SIRs of 53.8 and 6.6, respectively); and invasive vaginal, vulvar, and rectal cancers (SIRs of 29.9, 5.7, and 2.2, respectively). Significantly elevated risks were observed across race and ethnic populations for subsequent vaginal in situ (SIR for whites of 49.4; blacks, 52.8; Asian/Pacific Islander [API], 91.4; and Hispanics, 55.7) and invasive cancers (SIR for whites of 25.7; blacks, 34.5; API, 48.5; and Hispanics, 25.2). The results of the current study demonstrate a substantially increased risk of the development of subsequent primary in situ and invasive cancers among cervical cancer survivors and have implications for the development of prevention and early detection strategies as the role of HPV infection becomes evident.
Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) ... more Epidemiologic studies have implicated estrogenic exposure as well as human papilloma virus (HPV) infection in cervical carcinogenesis, and some studies have suggested that estrogen and HPV may play synergistic roles in cervical tumorigenesis. In this study, we report a novel finding that f35% of cervical carcinomas tested (n = 19) express aromatase, the enzyme responsible for converting androgen to estrogen, the ratelimiting and final step in estrogen biosynthesis. On the other hand, no aromatase expression was detected in precancerous (n = 42) or normal cervical (n = 17) tissue samples. Increased aromatase was associated with increases in estrogen receptors (ER-A and ER-B) and a decrease in progesterone receptor levels, suggesting that in situ estrogen signaling via ER may be involved in tumor growth. Stable overexpression of aromatase in HPV cervical cancer cells resulted in increased cellular proliferation, anchorage-independent growth, and ER expression and activity. In contrast...
Gay, bisexual, and other men who have sex with men (MSM) experience disproportionately high burde... more Gay, bisexual, and other men who have sex with men (MSM) experience disproportionately high burdens of Human Papilloma Virus (HPV)-associated anal cancers. Recent focus has shifted to anorectal cancer prevention through high-resolution anoscopy (HRA); however, little is known about sexual minority men’s perceptions, attitudes, or beliefs regarding HRA. We conducted 4 qualitative Focus Group Discussions (FGDs) (n = 15) with sexual minority men, focusing on their beliefs, attitudes, and perceptions of undergoing HRA. Participants discussed their experiences of HPV/HRA as influenced by both their gender and sexuality, including unawareness of HPV disease as a male health issue, challenges relating to female-oriented HPV/HRA language, conception of HPV/HRA as related to prostate health, and connecting their sexual behavior identification as “bottoms” to their need for HRA. As efforts to improve HRA knowledge, access, and uptake among sexual and gender minority communities increase, spec...
A86 Background: Women diagnosed with cervical cancer tend to have specific risk factors for devel... more A86 Background: Women diagnosed with cervical cancer tend to have specific risk factors for developing a cancer later in life: infection with the Human Papillomavirus (HPV), history of smoking, and/or treatment with radiation therapy. Recent licensure of an HPV vaccine protecting against HPV 16 and 18 has raised the issue of whether current racial/ethnic disparities in cervical cancer will improve or worsen. Since the HPV vaccine has the ability to impact more than one HPV-related cancer in the same individual, we examine whether there are racial/ethnic differences in developing subsequent primary cancers (invasive and in situ) after an initial invasive cervical cancer diagnosis. Methods: Using the SEER 13 Cancer Registry data (1992-2004), we identified 23,059 women with invasive cervical cancer and observed subsequent malignancies (including some in situ) in that cohort during 4.75 mean person-years of follow-up. We focused on HPV-associated cancers (vaginal, vulvar, anal, rectal,...
Objective The aim of the study was to describe the incidence and correlates of atypical glandular... more Objective The aim of the study was to describe the incidence and correlates of atypical glandular cell (AGC) Pap tests in a low socioeconomic status, underserved population. Materials and Methods Medical records of patients with AGC Pap tests at a single institution were reviewed from January 2013 to August 2019. Baseline characteristics were extracted including age, body mass index, birth control, abnormal uterine bleeding, and human papillomavirus (HPV). All colposcopy and endometrial biopsies were classified into negative/low-risk (polyps, tubular metaplasia, microglandular hyperplasia, cervical intraepithelial neoplasia 1) and high-risk (HR) lesions (cervical intraepithelial neoplasia 2/3, adenocarcinoma in situ, endometrial hyperplasia, cervical cancer, endometrial cancer). Logistic regression identified significant associations. Sixty-eight randomly selected AGC cytology slides from the cohort and 32 non-AGC slides outside the cohort were blindly reviewed by 6 pathologists. Fleiss κ interrater agreement was assessed. Results Seven hundred forty patients with AGC Pap tests were identified (0.8% of all Pap tests performed during this time). After excluding for incomplete data, 478 patients were included. Sixty-three patients had HR lesions (13.3%). Patients with HR lesions had increased odds of abnormal uterine bleeding (odds ratio = 4.32, p < .001) and HPV positivity (odds ratio = 10.89, p < .001) when compared with patients with low-risk lesions. The κ agreement was 0.21 for all cases and 0.18 for AGC alone. Conclusions This population falls within the national averages for AGC Pap tests. There was an increased risk of HR lesions in patients with abnormal uterine bleeding and HPV positivity. The rate of HR lesions among AGC Pap tests was at the lower end of values in the literature. After blinded pathologist review, interobserver κ agreement was low for AGC Pap tests.
IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point ... more IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and C...
ABSTRACT The American Cancer Society (ACS) released updated cervical cancer screening guidelines ... more ABSTRACT The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.
Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomav... more Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods We enrolled n = 865 WLWH (323 from the Women’s Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[−]/Pap[−] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histo...
Uploads
Papers