Lucie Gregoire

Publications (16)36.77 Total impact

• Article: Human papillomavirus, cervical cancer and women's knowledge.

  Azadeh Stark, Lucie Gregoire, Rebecca Pilarski, Allison Zarbo, Arthur Gaba, Wayne D Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: Human papillomavirus (HPV) is the major risk factor for cervical cancer. We implemented a retrospective case-series study to discern HPV knowledge accuracy among women diagnosed with and treated for cervical cancer. Cases (n=1174), identified from the Pathology database, were diagnosed and treated for cervical cancer at the same institution. Data were collected using self-administered questionnaires and by reviewing medical records. A total of 328 (27.9%) women returned the completed forms. Only 19% of the respondents had identified HPV as the primary risk factor for cervical cancer. Environmental pollutants, radiation exposure, poor dietary habits, excessive physical activity and family history of cervical cancer were listed as risk factors among many others. Multivariate analysis was performed to determine variables that were best associated with HPV knowledge accuracy. Age and education were the two variables that were statistically associated with the outcome. Younger and more educated women who participated in this study were more likely to know about the association between HPV infection and the risk of cervical cancer. Cervical cancer risk factor knowledge, especially knowledge about HPV is low, even among women with the history of cervical cancer. Younger and more educated women are more likely to have HPV and cervical cancer knowledge accuracy. The importance of personal health practices and the focus on health education should be equally emphasized to achieve successful cancer prevention through vaccination.
  Cancer Detection and Prevention 02/2008; 32(1):15-22. · 2.52 Impact Factor
• Article: HLA-DQA is associated with abdominal aortic aneurysms in the Belgian population.

  Gerard Tromp, Toru Ogata, Lucie Gregoire, Katrina A B Goddard, Magdalena Skunca, Wayne D Lancaster, Antonio R Parrado, Qing Lu, Hidenori Shibamura, Natzi Sakalihasan, Raymond Limet, Gerald L Mackean, Claudette Arthur, Taijiro Sueda, Helena Kuivaniemi
  [show abstract] [hide abstract]
  ABSTRACT: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with human leukocyte antigen (HLA) polymorphisms (HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles) in 387 AAA cases and 426 controls. We observed an association with the HLA-DQA1 locus among Belgian males, and found a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases and controls. In conclusion, this study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.
  Annals of the New York Academy of Sciences 12/2006; 1085:392-5. · 3.15 Impact Factor
• Source

  Available from: Gerard Tromp

  Article: Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study.

  Toru Ogata, Lucie Gregoire, Katrina A B Goddard, Magdalena Skunca, Gerard Tromp, Wayne D Lancaster, Antonio R Parrado, Qing Lu, Hidenori Shibamura, Natzi Sakalihasan, Raymond Limet, Gerald L MacKean, Claudette Arthur, Taijiro Sueda, Helena Kuivaniemi
  [show abstract] [hide abstract]
  ABSTRACT: Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.
  BMC Medical Genetics 02/2006; 7:67. · 2.33 Impact Factor
• Article: Evidence for association between the HLA-DQA locus and abdominal aortic aneurysms in the Belgian population: a case control study

  Toru Ogata, Lucie Gregoire, Katrina Goddard, Magdalena Skunca, Gerard Tromp, Wayne Lancaster, Antonio Parrado, Qing Lu, Hidenori Shibamura, Natzi Sakalihasan, Raymond Limet, Gerald MacKean, Claudette Arthur, Taijiro Sueda, Helena Kuivaniemi
  [show abstract] [hide abstract]
  ABSTRACT: Abstract Background Chronic inflammation and autoimmunity likely contribute to the pathogenesis of abdominal aortic aneurysms (AAAs). The aim of this study was to investigate the role of autoimmunity in the etiology of AAAs using a genetic association study approach with HLA polymorphisms. Methods HLA-DQA1, -DQB1, -DRB1 and -DRB3-5 alleles were determined in 387 AAA cases (180 Belgian and 207 Canadian) and 426 controls (269 Belgian and 157 Canadian) by a PCR and single-strand oligonucleotide probe hybridization assay. Results We observed a potential association with the HLA-DQA1 locus among Belgian males (empirical p = 0.027, asymptotic p = 0.071). Specifically, there was a significant difference in the HLA-DQA1*0102 allele frequencies between AAA cases (67/322 alleles, 20.8%) and controls (44/356 alleles, 12.4%) in Belgian males (empirical p = 0.019, asymptotic p = 0.003). In haplotype analyses, marginally significant association was found between AAA and haplotype HLA-DQA1-DRB1 (p = 0.049 with global score statistics and p = 0.002 with haplotype-specific score statistics). Conclusion This study showed potential evidence that the HLA-DQA1 locus harbors a genetic risk factor for AAAs suggesting that autoimmunity plays a role in the pathogenesis of AAAs.
  BMC Medical Genetics. 01/2006;
• Article: Sequential molecular and cellular events during neoplastic progression: a mouse syngeneic ovarian cancer model.

  Paul C Roberts, Emilio P Mottillo, Andrea C Baxa, Henry H Q Heng, Nicole Doyon-Reale, Lucie Gregoire, Wayne D Lancaster, Raja Rabah, Eva M Schmelz
  [show abstract] [hide abstract]
  ABSTRACT: Studies performed to identify early events of ovarian cancer and to establish molecular markers to support of early detection and the development of chemopreventive regimens have been hindered by a lack of adequate cell models. Taking advantage of the spontaneous transformation of mouse ovarian surface epithelial (MOSE) cells in culture, we isolated and characterized distinct transitional stages of ovarian cancer as the cells progressed from a premalignant nontumorigenic phenotype to a highly aggressive malignant phenotype. Transitional stages were concurrent with progressive increases in proliferation, anchorage-independent growth capacity, in vivo tumor formation, and aneuploidy. During neoplastic progression, our ovarian cancer model underwent distinct remodeling of the actin cytoskeleton and focal adhesion complexes, concomitant with downregulation and/or aberrant subcellular localization of two tumor-suppressor proteins E-cadherin and connexin-43. In addition, we demonstrate that epigenetic silencing of E-cadherin through promoter methylation is associated with neoplastic progression of our ovarian cancer model. These results establish critical interactions between cellular cytoskeletal remodeling and epigenetic silencing events in the progression of ovarian cancer. Thus, our MOSE model provides an excellent tool to identify both cellular and molecular changes in the early and late stages of ovarian cancer, to evaluate their regulation, and to determine their significance in an immunocompetent in vivo environment.
  Neoplasia 11/2005; 7(10):944-56. · 5.95 Impact Factor
• Article: Integration of human papillomavirus type 11 in recurrent respiratory papilloma-associated cancer.

  Patrick M Reidy, Herbert H Dedo, Raja Rabah, Jayson B Field, Robert H Mathog, Lucie Gregoire, Wayne D Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: The main objective was to demonstrate that human papillomavirus (HPV) type 11 is an aggressive virus that plays a significant role in the development of laryngeal cancer in patients with a history of recurrent respiratory papillomatosis (RRP). We have done so by preliminary investigation into the molecular mechanism underlying the malignant transformation of RRP to invasive squamous cell carcinoma. An experimental, nonrandomized, retrospective study using tissue specimens from nine patients with a history of RRP that progressed to laryngeal or bronchogenic cancer was performed. DNA and RNA were extracted from 20 formalin-fixed, paraffin-embedded specimens from six patients with a history of early onset RRP and laryngeal cancer and from three patients with early onset RRP and bronchogenic cancer. Polymerase chain reaction (PCR) was performed on DNA to determine the HPV type in each specimen. Reverse-transcriptase PCR specific for virus transcripts was performed on RNA to determine whether the viral genome was integrated into the host genome. HPV-11 but not HPV-6, 16, or 18 was found in all of the laryngeal and bronchogenic cancers in patients with a history of early onset RRP in this study. RNA, sufficiently intact for examination, was obtained from seven patients. Analysis of HPV 11 transcripts revealed integration of the viral genome in three of seven patients. HPV type 6 and 11 are considered "low-risk" viruses and are not associated with genital cancers, as are HPV types 16 and 18. However, our data suggests that HPV type 11 is an aggressive virus in laryngeal papilloma that should be monitored in patients with RRP.
  The Laryngoscope 12/2004; 114(11):1906-9. · 1.75 Impact Factor
• Article: HLA-DQ alleles in white and African American patients with juvenile-onset recurrent respiratory papillomatosis.

  Lucie Gregoire, Patrick M Reidy, Raja Rabah, Wayne D Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: To determine HLA-DQalpha and -DQbeta1 allele associations in juvenile-onset recurrent respiratory papillomatosis (RRP) for risk, disease course, and human papillomavirus type. A nonrandomized controlled study was performed on DNA extracted from papilloma specimens of children with a history of RRP, and from peripheral blood of African American and white children without RRP. The frequencies of DQalpha and DQbeta1 alleles were compared between patients and ethnically matched controls. Records of 48 children treated for RRP at Children's Hospital of Michigan in Detroit (26 African American and 22 white) were reviewed. Control subjects consisted of 80 African American and 80 white children seen at the hospital for conditions other than RRP. African American and white patients with DQbeta1*050X (not *0501, *0502, *0503, *0504, or *0505) were at higher risk to develop RRP than controls (P =.01 and.03, respectively). DQbeta1*0402 was protective for African Americans (P =.01). Whites with DQalpha*0102 were at risk for RRP (P =.03). This allele was associated with disease remission in African Americans (P =.03). DQalpha*0101/0104 conferred protection in whites (P =.047). No association was seen for allele frequency and human papillomavirus type. Whites with haplotype DQalpha*0501/DQbeta1*0201 were at high risk for RRP (P =.002). No relationships were seen for African Americans or whites between haplotype frequencies and disease course or human papillomavirus type. HLA-DQalpha and -DQbeta1 alleles occur at different frequencies in African American and white children with RRP than controls. Specific alleles influence risk for RRP. Allele and haplotype frequencies have some influence on disease course, but were independent of human papillomavirus type.
  Archives of Otolaryngology - Head and Neck Surgery 12/2003; 129(11):1221-4. · 1.63 Impact Factor
• Article: The Bali STD/AIDS study: human papillomavirus infection among female sex workers.

  Kathleen Ford, Barbara D Reed, Dewa Nyoman Wirawan, Partha Muliawan, Made Sutarga, Lucie Gregoire
  [show abstract] [hide abstract]
  ABSTRACT: Female sex workers in low priced brothel areas in Denpasar, Bali, Indonesia participated in an intervention study designed to promote condom use and sexually transmitted disease (STD)/AIDS prevention. The intervention provided educational sessions for sex workers, STD treatment for sex workers, condom distribution, and media for clients. The brothel areas were divided into high and low areas for programme effort. The high effort areas received a more intensive behavioural intervention than the low effort areas. A clinic was available for STD treatment in both areas. Behavioural surveys and STD testing were used to evaluate the programmes. About 600 were evaluated for several STDs and completed personal interviews at enrolment and at six-month intervals during the 18-month study. About 50% of women were new to the study at each round. Human papillomavirus (HPV) testing of cervical swabbed specimens, using polymerase chain reaction methodology, was performed at the beginning of the study and 18 months later. Human papillomavirus infection was initially high in these women (38.3%) and declined to 29.7% after 18 months (P <0.01). The prevalence of HPV infection declined with age (P <0.01). HPV infection was associated with a number of STD symptoms that were reported in personal interviews. These associations were stronger in the first time period. Infection with Neisseria gonorrhoeae was associated with HPV infection at baseline (P =0.03). HPV infection declined in the study area with the more intensive educational programme (P <0.01). The prevalence of HPV infection declined over time and was associated with study area and age of woman.
  International Journal of STD & AIDS 10/2003; 14(10):681-7. · 1.09 Impact Factor
• Article: Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas.

  Leticia B A Rangel, Rachana Agarwal, Theresa D'Souza, Ellen S Pizer, Piero L Alò, Wayne D Lancaster, Lucie Gregoire, Donald R Schwartz, Kathleen R Cho, Patrice J Morin
  [show abstract] [hide abstract]
  ABSTRACT: Claudin proteins represent a large family of integral membrane proteins crucial for tight junction (TJ) formation and function. Claudins have been shown to be up-regulated in various cancers and have been suggested as possible biomarkers and targets for cancer therapy. Because claudin-3 and claudin-4 have been proposed to be expressed in epithelial ovarian cancer, we have performed a detailed analysis of CLDN3 and CLDN4 expression in a panel of ovarian tumors of various subtypes and cell lines. We also investigated whether high expression of claudin-3 and claudin-4 was associated with TJ function in ovarian cancer cells. Experimental Design: RNA was obtained from a panel of 39 microdissected epithelial ovarian tumors of various histological subtypes for real-time reverse transcription-PCR analysis. In addition, a total of 70 cases of ovarian carcinomas, ovarian cysts, and normal ovarian epithelium from a tissue array were analyzed by immunohistochemistry. Finally, a panel of cell lines was used for Western analysis of claudin expression and TJ permeability studies. Although expressed at low levels in some normal human tissues, including the ovary, CLDN3 and CLDN4 are highly up-regulated in epithelial ovarian cancers of all subtypes. Immunohistochemical analyses using our ovarian tissue array confirmed the high level of expression of claudin-3 and claudin-4 in the majority of ovarian carcinomas, including many tumors exhibiting cytoplasmic staining. Ovarian cystadenoma did not frequently overexpress these proteins, suggesting that the expression of these proteins is associated with malignancy. In ovarian cancer cell lines, claudin-3 and claudin-4 expression was not associated with functional TJs as measured by transepithelial electrical resistance. These results show that CLDN3 and CLDN4 are frequently up-regulated in ovarian tumors and cell lines and may represent novel markers for this disease. Overexpression of these genes in ovarian cancer also suggests interesting scenarios for the involvement of TJ in tumorigenesis. A better knowledge of the mechanisms underlying ovarian tumorigenesis will likely result in the development of novel approaches for the diagnosis and therapy of this deadly disease.
  Clinical Cancer Research 08/2003; 9(7):2567-75. · 7.74 Impact Factor
• Article: Organotypic culture of human ovarian surface epithelial cells: A potential model for ovarian carcinogenesis

  Lucie Gregoire, Adnan Munkarah, Raja Rabah, Robert T. Morris, Wayne D. Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: The objective of this work was to establish an in vitro multidimensional culture system for human ovarian surface epithelial (HOSE) cells as a model for ovarian carcinogenesis. The epithelial origin of cell outgrowth from cells obtained from the ovarian surface was confirmed by keratin staining. Two cultures from two different patients were established, HOSE-A and HOSE-B. Cultures were infected with a retrovirus expressing human papillomavirus genes E6 and E7 to extend their life span. HOSE cells were seeded onto collagen gels containing NIH3T3-J2 fibroblasts as feeder cells and grown to confluence submerged in growth medium. The collagen bed was then raised to the air-medium interface for 7 d (organotypic culture). Microscopically, fixed cultures revealed a single layer of flat cells growing on the collagen surface, reminiscent of HOSE cells in vivo. Infected HOSE-A and HOSE-B cells exhibited aberrant growth because they stratified. In addition, established ovarian cancer lines grown in this fashion stratified and showed malignant phenotypes. Thus, cells grown in organotypic culture resemble their in vivo counterparts, providing a basis for establishing a system to study growth, proliferation, differential gene expression, and perhaps malignant transformation of HOSE cells.
  In Vitro Cellular & Developmental Biology - Animal 01/1998; 34(8):636-639. · 1.31 Impact Factor
• Article: Surrogate endpoint biomarkers for cervical cancer chemoprevention trials

  MPH Mack T. Ruffin IV MD, Mohammed S. Ogaily MD, Carolyn M. Johnston MD, Lucie Gregoire PhD, Wayne D. Lancaster PhD, Dean E. Brenner MD, Mack T. Ruffin IV, Mohammed S. Ogaily, Carolyn M. Johnston, Lucie Gregoire, Wayne D. Lancaster, Dean E. Brenner
  [show abstract] [hide abstract]
  ABSTRACT: Cervical intraepithelia neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve as both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention of progression. In planning chemopreventive trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression.If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant.
  Journal of Cellular Biochemistry 12/1994; 59(S23):113 - 124. · 2.87 Impact Factor
• Article: Association between HLA‐DQB1 alleles and risk for cervical cancer in African‐American women

  Lucie Gregoire, W. Dwayne Lawrence, Debra Kukuruga, A. Bradley Eisenbrey, Wayne D. Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: Squamous-cell carcinoma of the cervix and its precursor lesions are associated with human papillomavirus (HPV) infection. Epidemiological studies indicate that HPV infection in itself is not sufficient for cervical-cancer induction, suggesting that other factors contribute to carcinogenesis. We have investigated the potential role of host genetic background as one such factor. We screened a series of squamous-cell carcinomas of the cervix for HLA-class-II DQBI* alleles by the polymerase chain reaction and site-specific oligonucleotide probe hybridization and for HPV type from African-American women using a local, ethnically matched control panel. Statistically significant associations for increase in relative risk for cervical cancer were seen for DQBI*0303 and DQBI*0604. DQBI*0201 and the hetero-zygote DQBI*0301/*0501 showed a decrease in relative risk for cervical cancer. HPV typing revealed no association between virus type and DQBI alleles. Our results confirm other studies showing an increase in relative risk for cervical cancer associated with HLA-DQ3 alleles in Caucasians. © 1994 Wiley-Liss, Inc.
  International Journal of Cancer 05/1994; 57(4):504 - 507. · 5.44 Impact Factor
• Article: Preferential Association of Human Papillomavirus With High-Grade Histologic Variants of Penile-Invasive Squamous Cell Carcinoma

  Lucie Gregoire, Antonio L Cubilla, Victor E Reuter, Gabriel P. Haas, Wayne D Lancaster
  [show abstract] [hide abstract]
  ABSTRACT: Background Human papillomavirus (HPV) is causally associated with cervical squamous cell carcinoma (SCC) and its precursor lesions. By analogy, HPV is believed to play a role in penile cancer through progression of HPV-associated penile squamous intraepithelial lesions (SIL). HPV DNA has been reported to be present in 100&percnt; of highgrade penile SIL, but the percentage of invasive or infiltrating penile SCC that was positive for HPV DNA has varied from study to study (positivity values ranging from 32&percnt; to 82&percnt;). Purpose To ascertain whether HPV is associated with penile cancer, we used a polymerase chain reaction (PCR)-based assay to test specimens of penile SCC for the presence of HPV DNA. Methods A total of 117 formalin-fixed, paraffin-embedded specimens of penile cancer from an equal number of patients who had been diagnosed either at the Memorial Sloan-Kettering Cancer Research Center in New York City between 1964 and 1992 or the Universidad Nacional de Asunción in Paraguay between 1980 and 1992 were analyzed. Specimens were examined without prior knowledge of the histology of the lesions. Methods were used that minimized sample contamination, thus avoiding false-positive results. PCR and Southern blot analyses were used to determine HPV type. The presence of HPV DNA was studied for association with the tumor properties histopathology, growth pattern, tumor grade, regional lymph node status, and anatomic location. Two-sided statistical tests were used to determine P values. Results HPV DNA was detected in 26 (22.2&percnt;) of 117 specimens. In 23 (88.5&percnt;) of the 26 HPV-positive specimens, HPV type 16 (only) was identified. HPV DNA was frequently associated with SCC in areas showing basaloid and&sol;or warty changes (nine [47.4&percnt;] of 19 specimens were HPV positive; P &equals; .0125). More highly significant was the association of virus with basaloid SCC (nine [75&percnt;] of 12 specimens were HPV positive; P &equals; .0005). However, HPV was not found to be associated with typical SCC of the penis (five [11.1&percnt;] of 45 specimens were HPV positive). Virus DNA was more often associated with high-grade tumors ( P &equals; .0278) exhibiting aggressive growth ( P &equals; .0382) localized to the glans penis ( P &equals; .0324). Stepwise logistic regression analysis revealed that only tumor histopathology was a significant predictor of an HPV association. Conclusions The presence of HPV DNA was found to be significantly associated only with those penile SCC exhibiting basaloid changes. Furthermore, HPV DNA sequences tended to be associated with higher grade and more aggressive tumor localized to the glans penis. The low frequency of HPV in penile SCC implies that only a small proportion of these cancers arise from HPV-associated penile SIL. [J Natl Cancer Inst 1995;87:1705–9]
• Article: E6 and E7 oncogene expression by human papilloma virus (HPV) and the aggressive behavior of recurrent laryngeal papillomatosis (RLP).

  Bahig M Shehata, Kristen J Otto, Steven E Sobol, Christina A Stockwell, Cora Foulks, Wayne Lancaster, Lucie Gregoire, Charles E Hill
  [show abstract] [hide abstract]
  ABSTRACT: Recurrent laryngeal papillomatosis (RLP), a chronic disease associated with human papilloma virus (HPV), requires serial surgical procedures for debulking, resulting in debilitating long-term dysphonia, laryngeal scarring, and rarely malignant degeneration. Human papilloma virus 11 tumors have been widely accepted as more aggressive than HPV 6 tumors; however, the clinical course has been difficult to predict at disease onset, and the biologic mediators of proliferation have not been well characterized. A retrospective case review of 43 patients (4 months to 10 years at diagnosis) was performed on children treated for recurrent laryngeal papillomatosis. Patient charts were reviewed for demographic information, age at RLP diagnosis, approximate frequency of surgical intervention, and absolute number of surgical procedures performed. Human papilloma virus subtyping was performed. Expression analysis of the HPV-encoded E6 and E7 oncogenes was performed by reverse-transcriptase polymerase chain reaction. Fourteen patients had subtype 11 (33%) and 29 patients had subtype 6 (67%). As expected, HPV 11 patients showed a more aggressive clinical course than HPV 6 patients. However, 38% of patients with subtype 6 (11 patients) followed a clinical course that mirrored the more severe subtype 11 patients. These patients expressed the disease at a younger age (P < 0.0002) and showed higher levels of E6 and E7 oncogenes compared to the patients with the more indolent course. Although HPV subtype and early onset of RLP are well characterized prognostic factors, our study documents the significance of E6 and E7 oncogene expression as potential biologic mediators of proliferation and thereby clinical behavior.
  Pediatric and Developmental Pathology 11(2):118-21. · 0.99 Impact Factor
• Source

  Available from: umich.edu

  Article: Surrogate endpoint biomarkers for cervical cancer chemoprevention trials

  Mack T Ruffin, Mohammed S. Ogaily, Carolyn M. Johnston, Lucie Gregoire, Wayne D Lancaster, Dean E Brenner
  [show abstract] [hide abstract]
  ABSTRACT: Cervical intraepithelia neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve as both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention of progression. In planning chemopreventive trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/38459/1/240590915_ftp.pdf
• Article: Human papillomavirus infection in “young” versus “old” patients with squamous cell carcinoma of the head and neck

  Elizabeth A. Sisk, Carol R Bradford, Abraham Jacob, Christopher H. Yian, Kim M. Staton, Gong Tang, Monte O. Harris, Thomas E Carey, Wayne D Lancaster, Lucie Gregoire
  [show abstract] [hide abstract]
  ABSTRACT: Background Human papillomavirus (HPV) represents a potential risk factor for squamous cell cancer of the head and neck (SCCHN). We evaluated the prevalence of HPV DNA in patients with SCCHN diagnosed at the University of Michigan from 1994–1996. Methods Patients were stratified by age at diagnosis as “young” (<50 years; median, 39) or “old” (>50 years; median, 66). Fourteen “young” and 14 “old” were matched for tumor site, and 4 additional “old” patients were included. Specimens were analyzed by polymerase chain reaction for HPV DNA using 2 sets of consensus primers. HPV sequences were confirmed by Southern blot hybridization and typed with type-specific probes. Results Overall, 15 of 32 (46.9%) samples contained HPV sequences. HPV 16 was detected in 9 of 15 (60%), HPV-18 in 1 of 15 (6.6%), and 5 of 15 (33.3%) remained untyped by multiple methods. When stratified, 7 of 14 (50%) “young” were HPV-positive compared with 8 of 18 (44.4%) “old” ( p = .76). Survival in patients with HPV-positive SCCHN was significantly longer than that for HPV-negative patients. Conclusions The incidence of HPV in “young” versus “old” is not significantly different, suggesting similar roles for both groups. Patients with HPV-positive tumors may have a survival advantage relative to patients with HPV-negative tumors. © 2000 John Wiley & Sons, Inc. Head Neck 22: 649–657, 2000. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/35115/1/2_ftp.pdf