Abnormal Pap Test Research Articles

Abstract 3611: Benzo(a)pyrene exposure increases expression of HPV oncoproteins: a potential co-factor for increased cervical cancer among Northern Plains American Indian women.

Abstract Introduction: Cervical cancer remains one of the most common and deadly cancers in women worldwide. There is a significant health disparity in the incidence and mortality of cervical cancer between American Indian and Caucasian women residing on the Northern Plains. The development of cervical cancer is closely associated with persistent infection with high risk HPV genotypes. Additionally, exposure to cigarette smoke is also a risk factor for cervical cancer. Our studies indicate that Northern Plains American Indian women have a high rate of both HPV infection and smoking. Our studies also show that American Indian women who tested positive for HPV were more likely to have an abnormal PAP test than HPV positive Caucasian women. While smoking is known to increase the risk of developing cervical cancer, the molecular interactions between HPV and smoke carcinogens are not well known. Herein, we determine the cellular and molecular effects of benzo-a-pyrene (BaP) (a carcinogen in cigarette smoke) on HPV oncoprotein expression in cervical cancer cells and elucidate the role of the aryl hydrocarbon receptor (AhR) in this process. Methods: The effects of BaP on HPV oncoproteins and AhR mediated molecular events was determined using cervical cancer cell line models and real time PCR, immunoblotting, immunostaining and flow cytometry analyses. The level of AhR activation in normal cervix and in cervical cancer tissues was also determined with immunohistochemical analysis. Results: Our results indicate that exposure to BaP, a tobacco carcinogen, activates the AhR pathway in a time and dose dependent manner, as determined by an increase in nuclear localization of AhR and increased expression of cytochrome p450 1A. Expsoure to BaP ultimately results in increased expression of HPV oncogenes. Importantly, curcumin, a natural compound, attenuated the BaP induced increase in the expression of HPV E7 oncoprotein. Interestingly, both cytoplasmic and nuclear localization of AhR is increased in cervical cancer tissue compared to normal cervical epithelium. Conclusion: Taken together this data imply that a high prevalence of HPV infection and a high exposure rate to BaP may synergize to increase the incidence and mortality of cervical cancer in American Indian women residing in the Northern Plains. We have identified curcumin as a potent compound that may be effective in attenuating oncogenic HPV infection. However, increased cervical cancer screening is warranted in addition to HPV vaccine and use of chemopreventive agents, such as curcumin, to effectively decrease the cervical cancer health disparity in Northern Plains American Indian women. Citation Format: Diane M. Maher, Maria Bell, Amanda Schaefer, Meena Jaggi, Subhash C. Chauhan. Benzo(a)pyrene exposure increases expression of HPV oncoproteins: a potential co-factor for increased cervical cancer among Northern Plains American Indian women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3611. doi:10.1158/1538-7445.AM2013-3611

Abstract 1351: A CD83 SNP is associated with abnormal Pap test results in high-risk Ohio Appalachian women.

Abstract Background: Invasive cervical cancer (ICC) is a leading cause of death in women worldwide. While the prevalence is decreasing in developing countries, it continues to disproportionately affect certain sub-populations in the US. For example, the rate of ICC incidence and mortality in Appalachian women is the highest in the US among white women. Further, Ohio Appalachian women also demonstrate 2-3 times higher rates of abnormal Pap smears compared to the general US population. While many risk factors are known to influence ICC development, little is known about the role of heredity and genetic susceptibility factors. The CD83 gene encodes a transmembrane glycoprotein known to play an important role in immune function. Previous studies suggest that a single nucleotide polymorphism (SNP) in CD83 is associated with increased susceptibility to cervical cancer development. The association was further increased in cervical cancer patients infected any high-risk HPV subtype. Objective: To determine if the CD83 SNP rs750749 is associated with abnormal Pap results and HPV infection in a population-based case control study of Ohio Appalachian women. Methods: The rs750749 SNP was genotyped from blood DNA derived from 288 abnormal Pap cases and 535 normal Pap controls. Odds ratio estimates and 95% confidence intervals were determined using logistic regression. Results: Carriers of the major TT genotype exhibited a 42% increase in the odds of presenting with an abnormal Pap test result compared to carriers of the minor CT and CC genotypes (OR=1.42; 95% CI: 1.05-1.92; p=0.02). Stratifying by HPV status, HPV positive TT carriers exhibited a marginally significant increase of 56% [OR=1.56; 95% CI: 0.95-2.55; p=0.08]. After controlling for smoking, the odds of abnormal Pap results are increased by 35% for TT carriers [OR=1.35; 95% CI: 0.99-1.84; p=0.06]. Conclusions: These findings suggest an association between the CD83 SNP rs750749 and cervical premalignancy in high-risk Ohio Appalachian women. Further studies are needed to determine if the association is maintained in Appalachian ICC patients as well as the biological significance of CD83 in ICC development. Funding Sources: This study was supported by a grant from the National Cancer Institute (P50 CA015632), the Behavioral Measurement Shared Resource at The Ohio State University Comprehensive Cancer Center (National Cancer Institute Grant P30 CA016058) and the Clinical and Translational Science Award (NIH/NCRR Grant Number UL1-RR025755). Citation Format: Joe T. Perrault, Blessing E. Ogbemudia, Marta L. Sears, Cecillia R. DeGraffinreid, Danqi Zhu, Bo Lu, David E. Cohn, Thomas J. Knobloch, Mack T. Ruffin, Electra D. Paskett, Christopher M. Weghorst. A CD83 SNP is associated with abnormal Pap test results in high-risk Ohio Appalachian women. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1351. doi:10.1158/1538-7445.AM2013-1351

Potential Effects of Updated Pap Test Screening Guidelines and Adenocarcinoma In Situ of the Cervix

To review cases of adenocarcinoma in situ (AIS) at our institution to examine how updated guidelines affect the timing of diagnosis. We identified patients with AIS diagnosed between 1998 and 2010 using the International Classification of Diseases, 9 Revision, Clinical Modification, code 233.1. Diagnosis was confirmed by pathology review. We abstracted demographic data, dysplasia history, and modalities utilized for diagnosis and treatment. We identified 242 patients who met selection criteria. Two hundred eight (86%) had Pap test abnormalities at presentation. One hundred thirty-seven out of 208 (66%) patients with abnormal Pap test results had a squamous, rather than glandular, abnormality. The mean time from abnormal Pap test to diagnosis of AIS was 29 months in patients older than 30 years and was 21 months in patients 30 years or younger. In patients younger than 21 years, 16 out of 17 had abnormal screening Pap test results showing squamous lesions. Their subsequent treatment for squamous dysplasia ultimately led to the diagnosis of AIS. : Updated screening guidelines may prevent the expeditious diagnosis of AIS in females younger than 21 years and those aged 21-29 years, many of whom had normal Pap test results within 3 years of diagnosis. II.

Prevalence of High-Risk Cervical Human Papillomavirus and Squamous Intraepithelial Lesion in Nigeria

The prevalence of cervical cancer and high-risk human papillomavirus (HPV) in Nigerian women remains poorly studied. Our objective was to estimate the prevalence of high-risk HPV and associated squamous intraepithelial lesions (SILs) in Nigeria. After institutional review board approval, data collection was performed by volunteers of FaithCare, Inc, between 2004 and 2008 in 3 regions of Nigeria (Okene, Katari, and Abuja). Demographic data and ThinPrep Pap smears (Cytyc, Marlborough, MA) were collected from 410 women. Pap smears were analyzed for both the presence of SIL and HPV DNA. The prevalence of high-risk HPV and SIL was 15.6% and 6.8%, respectively. Of the 28 abnormal Pap tests, 42.9% had atypical squamous cells of undetermined significance, 39.3% had low-grade SIL, 14.3% had high-grade SIL, and 3.6% had atypical glandular cells. There was a strong association between high-risk HPV and SIL in both the combined (p < .001) and individual group data (p < .001, p = .013, and p < .001 for Okene, Abuja, and Katari, respectively). However, there were no statistically significant correlations between either high-risk HPV or presence of SIL and known risk factors including age, history of sexually transmitted disease, and the number of sexual partners. There was also no statistical difference in the prevalence of high-risk HPV and SIL among the 3 locations. A strong association exists between high-risk HPV and SIL. The prevalence of cervical high-risk HPV and SIL, however, did not vary in the 3 different locations and is consistent with reports from other regions in Africa.

Changes in cervical cancer screening behavior for women attending Pap Test Week clinics

ObjectiveThis retrospective study of all women who accessed the 2006 Manitoba Pap Test Week clinics was designed to determine factors associated with inadequate cervical cancer screening and changes in cervical cancer screening behavior.MethodsData were acquired using the CervixCheck Manitoba registry and an ancillary database of demographic information collected from clinic attendees.ResultsThe study included 1124 women. Of these, 53% (n = 598) were under-screened (no Pap test in the previous 2 years) prior to accessing the clinics. Logistic regression analyses demonstrated that older age (odds ratio [OR] = 1.02, 95% confidence interval [CI] 1.01–1.03), no doctor (OR = 1.4, 95% CI 1.05–1.54), and living in Canada < 1 year (OR = 5.5, 95% CI 2.73–11.12) were associated with being under-screened prior to accessing the Pap Test Week clinics. Thirty-seven percent (n = 223) of under-screened women demonstrated improved screening status subsequent to the 2006 Pap Test Week (had a subsequent Papanicolaou [Pap] test performed within 2 years) and these women were more likely to live in an urban setting (P = 0.003), be younger (P < 0.001), originate outside Canada (P = 0.006), have lived in Canada for less than 1 year (P = 0.006), and have had an abnormal Pap test result in 2006 (P < 0.001). Previously under-screened women were less likely to become adequately-screened subsequent to 2006 if they had a Pap test performed at a Pap Test Week clinic compared to having a Pap test performed elsewhere (37% versus 60%, P < 0.001).ConclusionThis study identified a subset of under-screened women accessing Pap Test Week clinics whose screening status might be most modifiable.

Five-Year Risk of CIN 3+ to Guide the Management of Women Aged 21 to 24 Years

Current US national guidelines recommend beginning screening at age 21 using Pap tests only, with cotesting starting at age 30. To inform the management of Pap test abnormalities among women aged 21 to 24 years, who have extremely low cancer risks, we compared risks of CIN 3+ among women aged 21 to 24 versus 25 to 29 years or 30 to 64 years. We estimated 5-year risks of CIN 3+ given different Pap test results, with human papillomavirus (HPV) triage of atypical squamous cells of undetermined significance (ASC-US), among 133,947 women aged 21 to 24 years, compared with 135,382 women aged 25 to 29 years and 965,360 women aged 30 to 64 years, between 2003 and 2010 at Kaiser Permanente Northern California. There were 3 cancers diagnosed during follow-up in women aged 21 to 24 years. After high-grade Pap results (0.6% of Pap results), the 5-year CIN 3+ risks among women aged 21 to 24 years were comparable to those aged 25 to 29 and 30 to 64 years (atypical glandular cells, 6.9% vs 14% vs 8.5%, p = .8; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion, 16% vs 24% vs 18%, p = .8; high-grade squamous intraepithelial lesion, 28% vs 28% vs 47%, p = .4). After low-grade squamous intraepithelial lesion, the 5-year CIN 3+ risk was lower among women aged 21 to 24 years (3.0%) than that among women aged 25 to 29 years (5.0%, p = .01) or aged 30 to 64 years (5.2%, p = .0002). Although the 5-year CIN 3+ risk after HPV-negative/ASC-US was similar across all 3 groups (0.57% vs 0.59% vs 0.43%, p = 1), risk after HPV-positive/ASC-US was lower among women aged 21 to 24 years (4.4%) than that among women aged 25 to 29 years (7.1%, p < .0001) or 30 to 64 years (6.8%, p < .0001). Women aged 21 to 24 years had almost zero cancer risk, and positive Pap test results predicted low CIN 3+ risk except for the 0.6% of women with high-grade Pap results. The generally low risk supports conservative management of women aged 21 to 24 years.

The mRNA-HPV Test Utilization in the Follow Up of HPV Related Cervical Lesions

The biomolecular follow up of Human Papilloma Virus (HPV) is widely investigated in patients treated for HPV related cervical lesions, since the HPV-mRNA test is more specific and have a higher positive predictive value for CIN2-3 in triage of high risk (HR) women and in follow-up of women treated for CIN2/3. We investigated, during a 5 years' study, a cohort of patients divided in: group 1, patients at high risk for HPV-infections, and group 2, women diagnosed for CIN2/3, Cervicocarcinoma in situ (CIS) and Adenocarcinoma in situ (AIS) and surgically treated. The overall scheduled follow up was repeated each 6 months by: Pap Test, HPV-DNA test, m-RNA-HPV test and, in case of CIN2/3, CIS and AIS, also by colposcopy and biopsy. The follow up involved a total of 203 women: 85 women with mRNA-HPV positive test and 118 patients surgically treated for CIN2/3, CIS and AIS. In the group 1, the long term follow up detected, after one year, 32 positive mRNA-HR HPV women and, of these, after more than 2 years, 37.5% developed CIN1 and 21.8% developed CIN2/3. Similarly, in the follow up of group two, women with abnormal Pap test showed positivity of mRNA HR-HPV in 71.4% of cases even after 6 months; 65% of these developed a CIN1 within 2.5 years and 20% had CIN2/3 after 2.3 years. Study results indicate either that patients with mRNA HR-HPV positive controls, on average, after 12 months are all at risk of progression to CIN1 and CIN2/3, or the higher specificity of mRNA-HPV test than Pap Test in follow up of surgical treated patients. This investigation confirmed a strong association between HR mRNA-HPV presence and risk of neoplastic progression.

Health Care Utilization in Women with Cervical Cancer and Cervical Intraepithelial Neoplasia

Purpose: The purpose of this study was to investigate the health care utilization in Korean women with cervical cancer and cervical intraepithelial neoplasia (CIN). Methods: This is a retrospective study. Data were collected using the insurance coverage data-base of Health Insurance Review and Assessment Service (HIRA) from January 1, 2006 to December 31, 2010. Women who were treated for cervical cancer and cervical intraepithelial were included in this study. The data were analyzed using descriptive statistics. Results: In 2006, women treated for cervical cancer and CIN were 27,109 and 18,794, respectively. The number constantly increased from 2006 to 2010. In particular, the prevalence among women with cervical cancer aged 80 years or over was found to increase. Claims for health care services increased. Conclusion: Even though new cases of cervical cancer in Korea is decreasing, the number of women being treated and the costs are constantly increasing. Cervical cancer patients are at an increased risk of negative health outcomes. Therefore, screening for cervical cancer should be enforced to promptly treat women with abnormal Pap tests and thus minimize the risks. Every effort should be made to increase awareness about the importance of Human Papilloma Vaccination and regular screening on a personal as well as community and governmental levels.

Frequency of Precancerous Changes and Cervical Cancer Recorded in Three Health Centres in Tuzla Canton in Period 2010-2011

Cervical cancer is the second most common cancer in the world and the leading cause of death. Frequency and mortality are significantly reduced thanks to cytological Papanicolau test (PAP). Regular PAP test can reduce approximately 80% of cases of this cancerAim of the study:To examine frequency of cervical cancer and changes of cervix, the age of risk for the changes and effect of frequency of PAP test.Materials and methods:3383 PAP (cytological) findings have been retrospectively ana lysed in three Health Centres of Tuzla Canton: Tuzla, Srebrenik and Sapna. During 2010 and 2011 protocols of Health Centers have been analyzed.Results:Analysis of 3383 smears detected the following: abnormal PAP tests in 20.8% (705) and without abnormalities in 79.1% (2678). Normal findings in 9.1% (311), inflammatory changes in 69.6% (2357), ASCUS in 12.9% (438), ASC-H in 0.3% (11), LSIL in 5.4% (183), HSIL in 1.4% (49) and Squamous cell carcinoma in 0.7% (24). Cervical cancer has mostly been found in women from Srebrenik 1.1% (15) and least in women from Tuzla 0.3%(4).The highest number of abnormal findings (ASCUS, ASC-H , LSIL, H SIL and Cc) was also found in women from Srebrenik 39.5% (279). The average age of the examinees with the cancer was 41.7. In 62.5% (15) of women PAP test was performed for the first time and they were diagnosed with cervical cancer. Cervical cancer hasn’t been found in women who had PAP test once a year or more.Conclusion:Women with the abnormal findings in their first PAP test and should be persuaded to accept the treatment in order to prevent development of cervical cancer.

Prevalence of cervical high-risk human papillomavirus infections in kidney graft recipients

Female kidney graft recipients are regarded as a group at risk of cervical cancer development. The objective of this study was to assess the prevalence of cervical high-risk human papilloma virus (HR-HPV) infection and cervical intraepithelial neoplasia (CIN) in female kidney graft recipients in comparison to healthy controls. We assessed the prevalence of HR-HPV and CIN in 60 female kidney graft recipients of reproductive age in outpatient care of the First Department of Obstetrics and Gynecology, Medical University of Warsaw. The control group consisted of 60 healthy women. Cervical swabs were analyzed with use of Amplicor HPV Roche Molecular Systems test, detecting DNA of 13 types of high-risk HPV: 6, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. HR-HPV was detected in 11/60 kidney recipients and 15/60 healthy women (p=0.37). There was no correlation between HR-HPV presence and immunosuppressive regimen, underlying disease, graft function, or time interval from transplantation. In both groups, higher prevalence of HR-HPV was observed in females with ≥2 lifetime sexual partners. Abnormal Pap test results in 2 kidney recipients (2 cases of HSIL) and 2 healthy women (LSIL and HSIL) required colposcopy-guided cervical biopsy, which in all cases revealed CIN2+. Female kidney graft recipients seem to be equally exposed to cervical infection with HPV of high oncogenic potential as the healthy population.

The Utility and Management of Vaginal Cytology After Treatment for Endometrial Cancer

To estimate the accuracy of vaginal cytology in postoperative surveillance for detecting recurrent endometrial cancer and to estimate the optimal management of squamous abnormalities detected in this setting. This review included women who underwent hysterectomy for endometrial cancer between January 1, 2006, and December 31, 2010, and had at least one postoperative Pap test. Clinical and demographic data were collected and outcomes including abnormal vaginal cytology, results of colposcopic examination, and endometrial cancer recurrence were assessed. A Cox regression model to estimate the risk of abnormal cytology was created. Sensitivity, specificity, and negative and positive predictive values of detecting vaginal recurrences were calculated. Four hundred thirty-three women contributed 2,378 Pap tests. At least one abnormal cytology result was found during follow-up of 55 (13%) women, representing 3% of all Pap tests. No recurrent endometrial cancers were diagnosed on the basis of isolated abnormal cytology. No cases of recurrent cancer were diagnosed in women with atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion (LSIL) Pap test results. In multivariable analysis, abnormal cytology was highly associated with prior postoperative radiation therapy (P<.001). The sensitivity, specificity, and positive and negative predictive values of an abnormal Pap test result in detecting a local recurrence are 40%, 87.9%, 7.3%, and 98.4%, respectively. Colposcopy is not needed after a Pap test result read as atypical squamous cells of undetermined significance or LSIL. III.

Comparison of the Cobas 4800 HPV Test and the Seeplex HPV4A ACE with the Hybrid Capture 2 Test

Background: It is well-known that persistent cervical infections with high-risk human papillomavirus (HPV) are related to the development of high-grade cervical intraepithelial neoplasia and invasive cervical cancer and that infection with HPV 16 and HPV 18 accounts for approximately 70% of all cases of invasive cervical cancer.Methods: We performed 3 HPV molecular tests―the Cobas 4800 HPV test, the Seeplex HPV4A ACE, and the hybrid capture 2 (HC2) test―in 146 cervical swab samples to compare between these three tests.Results: There was a concordance rate of 82.8% between the results of the Cobas 4800 HPV and the HC2 test and a concordance rate of 84.9% between the results of the Seeplex HPV4A ACE and the HC2 test. Between the Cobas 4800 HPV test and the Seeplex HPV4A ACE, there was a concordance rate of 89.6% in the detection of high-risk HPV between the results and a concordance rate of 98.7% in the detection of HPV 16 or 18. When an abnormal Pap test was defined as ≥low grade squamous intraepithelial lesion (LSIL), the sensitivity of the Cobas 4800 HPV test, the Seeplex HPV4A ACE and the HC2 test were 71.1%, 80.0%, and 88.9%, respectively, while their specificities were 76.4%, 74.5%, and 67.9%, respectively.Conclusions: The results of this study suggest that the Cobas 4800 HPV test and the Seeplex HPV4A ACE may be as effective as the HC2 test in detecting HR HPV and that the concordance between the results of the Cobas 4800 HPV test and the Seeplex HDV4A ACE may be higher in the detection of HPV 16 and HPV18 than concerning high-risk HPV.

Inconsistencies between medical records and patient-reported recommendations for follow-up after abnormal Pap tests.

Adherence with recommended follow-up after an abnormal Pap test is a critical step in the prevention of cervical cancer. Here, we focused on identifying inconsistencies between self-reported and health department record recommendations for follow-up. Self-reported recommendations for follow-up were collected by questionnaire from 519 women with abnormal Pap tests in rural Appalachia as part of a trial of the efficacy of patient navigation. Health department medical records were reviewed to collect healthcare provider recommendations. Measures of inconsistency (discordance) were calculated for overall recommendations and each of three particular follow-up recommendations: repeat Pap test, referral for further tests, and other gynecologist referral. The inconsistencies between the recommendation from the health department records and self-reports ranged from 15.0% (repeat Pap test) to 35.3% (gynecologist referral). Inconsistencies were most common among women with a history of abnormal Pap tests and those with more severe initial results. Recommendations for repeat Pap tests were correctly reported most often when the women recalled receiving a letter stating the results. Of greatest concern were the inconsistencies regarding recommendations for referral to a gynecologist. The more severe the Pap test result, the greater the odds of inaccurate self-reports of receiving a referral to a gynecologist for follow-up, p<0.001. Clinicians should be aware that patients with a history of abnormal results and severe Pap test abnormalities are at risk of misreporting recommendations for follow up.

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

BackgroundVaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+. MethodsAs part of a vaccine impact monitoring project (HPV-IMPACT), females 18–31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the ‘trigger Pap’. ResultsAmong 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR=.67, 95% CI: .48–.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21–23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24–26 year olds (29.0% vs. 19.6%, p=.001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p=.001) and publicly compared to privately insured women (38.1% vs. 17.4%, p<.0001). ConclusionWe found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.

Follow-up of Abnormal Pap and Human Papillomavirus (HPV) Tests

Follow-up of Abnormal Pap and Human Papillomavirus (HPV) Tests

The Influence of Abnormal Pap Test History Prior to Reflex HPV Test on the Subsequent Risk of CIN2+

The Influence of Abnormal Pap Test History Prior to Reflex HPV Test on the Subsequent Risk of CIN2+

Abstract A87: “I didn't know what to think. I thought I was going to die.” Latinas' understanding and attitudes toward an abnormal Pap test result.

Abstract Background and purpose: There is a disproportionate burden of cervical cancer among Latinas compared with non-Latino White women. This is thought to be attributed to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test. The purpose of this study is to assess knowledge, attitudes, barriers and facilitators to follow up after an abnormal Pap test result in Latinas. Study Design: We conducted 26 semi-structured interviews among Latinas aged 21 to 64 years old who had an abnormal Pap test result in rural Eastern Washington. Interviews were conducted in the participants' preferred language. Interviews were transcribed verbatim and uploaded into Atlas.ti for coding and analysis. Results/Outcome: One of the main themes that emerged as a potential barrier to follow up was misconceptions and secrecy around an abnormal Pap test result. Upon receiving the result, all women instantly believed they had cancer, and many felt desperate and embarrassed to talk to close family and friends. Transportation, lack of insurance and pain from the procedures were also mentioned as very important barriers to follow up. For those participants who had shared their result, family support was mentioned as a key facilitator to follow up. Interestingly, trusting oneself and having faith in God were also mentioned by some as facilitators to follow up. Within our participants, unlike previous studies, “Fatalismo” did not emerge as a barrier. Impact: Understanding the barriers and facilitators to follow up care after an abnormal Pap test as well attitudes and knowledge of the implications of an abnormal Pap test can help us improve the education and outreach strategies used in reaching the Latina population. Discussion: Latinas seem to have misconceptions about the implications of having an abnormal Pap. There are important cultural barriers that derive from these misconceptions that may be affecting the uptake and follow up of cervical cancer screening in this population. Our results will inform an intervention to increase cervical cancer screening in Latinas in Eastern Washington. Citation Format: Elizabeth Carosso, Javiera Martinez, Matthew Banegas, Gloria Coronado, Beti Thompson. “I didn't know what to think. I thought I was going to die.” Latinas' understanding and attitudes toward an abnormal Pap test result. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A87.

Abstract SS01-04: Objective and perceived risk of cervical cancer risk among Appalachian women.

Abstract Objectives: Appalachia is a geographic area with elevated cervical cancer incidence rates, yet little research has examined the accuracy of the cervical cancer risk perceptions of women living in this region. We examined the accuracy of Appalachian women's cervical cancer risk perceptions and identified factors correlated with accurate risk perceptions. Methods: Completed in 2006, we surveyed women (n=411) from Appalachian Ohio for the Community Awareness Resources Education (CARE) study. We calculated women's actual cervical cancer risk using the CARE Risky Sexual Behavior Index (classified as high, medium, or low risk), and women indicated their perceived risk of cervical cancer (classified as higher than, about the same as, or lower than other women). We used multivariate logistic regression to identify factors correlated with women accurately classifying their risk. Results: About 38% of women had high actual risk of cervical cancer, 31% had medium risk, and 31% had low risk. Most women (56%) perceived their risk of cervical cancer to be about the same as other women. About 38% of women accurately classified their cervical cancer risk. Women ages 31-50 (OR=1.77, 95% CI: 1.03-3.05; compared to women ages 51 and older) and those with a prior abnormal Pap test (OR=1.56, 95% CI: 1.01-2.39) were more likely to accurately perceive their cervical cancer risk. Conclusions: Most Appalachian women do not accurately perceive their risk of developing cervical cancer. This may be particularly true for older women and those who have no history of abnormal Pap tests. Education efforts are needed to help Appalachian women better understand their risk for cervical cancer, which may in turn help improve cervical cancer screening rates among this population. Citation Format: Electra D. Paskett, Nicolas P. Bons, Paul L. Reiter. Objective and perceived risk of cervical cancer risk among Appalachian women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr SS01-04.

Abstract B75: Benzo(a)pyrene exposure increases expression of HPV oncoproteins: A potential co-factor for increased cervical cancer among Northern Plains American Indian women.

Abstract Introduction: Cervical cancer remains one of the most common and deadly cancers in women worldwide. There is a significant health disparity in the incidence and mortality of cervical cancer between American Indian and Caucasian women residing on the Northern Plains. The development of cervical cancer is closely associated with persistent infection with high risk HPV genotypes. Additionally, exposure to cigarette smoke is also a risk factor for cervical cancer. Our studies indicate that Northern Plains American Indian women have a high rate of both HPV infection and smoking. Our studies also show that American Indian women who tested positive for HPV were more likely to have an abnormal PAP test than HPV positive Caucasian women. While smoking is known to increase the risk of developing cervical cancer, the molecular interactions between HPV and smoke carcinogens are not well known. Herein, we determine the cellular and molecular effects of benzo-a-pyrene (BaP) (a carcinogen in cigarette smoke) on HPV oncoprotein expression in cervical cancer cells and elucidate the role of the aryl hydrocarbon receptor (AhR) in this process. Methods: The effects of BaP on HPV oncoproteins and AhR mediated molecular events was determined using cervical cancer cell line models using real time PCR, immunoblotting, immunostaining and flow cytometry analyses. Additionally, following knockdown of AhR, cervical cancer cells lines were exposed to BaP and the levels of HPV oncoproteins and Cytochrome P450 1A (CYP1A1) were determined by flow cytometry, immunofluorescence and immunoblotting. Cervical cancer cells were also treated with curcumin to inhibit HPV oncoprotein expression. The level of AhR activation in normal cervix and in cervical cancer tissues was also determined with immunohistochemical analysis. Results: We show for the first time that exposure to Benzo-[a]-pyrene (BaP), a tobacco carcinogen, increases the expression of HPV E7 oncoprotein in both acute and extended treatment protocols. To address the mechanism of increased HPV E7 protein expression, we determined that BaP activates AhR in cervical cancer cells which may directly or indirectly increase HPV oncoprotein expression. AhR activation is increased in cervical cancer tissue compared to normal cervical epithelium. Importantly, curcumin, natural compound, attenuated the BaP induced increase in the expression of HPV E7 oncoprotein. Conclusion: Taken together this data imply that a high prevalence of HPV infection and a high exposure rate to BaP may synergize to increase the incidence and mortality of cervical cancer in American Indian women residing in the Northern Plains. We have identified curcumin as a potent compound that may be effective in attenuating oncogenic HPV infection. However, increased cervical cancer screening is warranted in addition to HPV vaccine and use of dietary agents, such as curcumin, to effectively decrease the cervical cancer health disparity in Northern Plains American Indian women. Citation Format: Diane M. Maher, Maria Bell, Amanda Schaefer, Emmylu O'Donnell, Meena Jaggi, Subhash Chauhan. Benzo(a)pyrene exposure increases expression of HPV oncoproteins: A potential co-factor for increased cervical cancer among Northern Plains American Indian women. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr B75.

Negative Predictive Value of Pap Testing

To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value. Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models. Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter). Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate. II.