Common use of Study Population Clause in Contracts

Study Population. The study was based at the San Francisco KPNC Anal Cancer Screening Clinic. We enrolled men who were identified as positive for HIV through the Kaiser HIV registry, who were aged ≥ 18 years, who were not diag- nosed with anal cancer before enrollment, and who pro- vided informed consent. In total, 363 men were enrolled between August 2009 and June 2010. The study was reviewed and approved by the institutional review boards at KPNC and at the National Cancer Institute. All partici- pants were asked to complete a self-administered ques- tionnaire to collect risk factor information. Additional information regarding HIV status and medication, sexu- ally transmitted diseases, and histopathology results were abstracted from the KPNC clinical database. For 87 of the 271 subjects without biopsy-proven AIN2 or AIN3 at the time of enrollment, follow-up infor- mation concerning outcomes from additional clinic visits up to December 2011 was available and included in the analysis to correct for the possible imperfect sensitivity of high-resolution anoscopy (HRA).13,15 Clinical Examination, Evaluation, and Results During the clinical examination, 2 specimens were col- lected by inserting a wet flocked nylon swab16 into the anal canal up to the distal rectal vault and withdrawing with rotation and lateral pressure. Both specimens were trans- ferred to PreservCyt medium (Hologic, Bedford, Mass). A third specimen was collected for routine testing for Chla- mydia trachomatis and Neisseria gonorrhea. After specimen collection, participants underwent a digital anorectal ex- amination followed by HRA. All lesions that appeared sus- picious on HRA were biopsied and sent for routine histopathological review by KPNC pathologists, and were subsequently graded as condyloma or AIN1 through AIN3. No cancers were observed in this study population. From the first specimen, a ThinPrep slide (Hologic) was prepared for routine Xxxxxxxxxxxx staining and xxxxx- xxxxx. Two pathologists (T.D. and D.T.) reviewed the slides independently. Cytology results were reported anal- ogous to the Bethesda classification17 for cervical cytology except when otherwise noted. The following categories were used: negative for intraepithelial lesion or malig- xxxxx (NILM); ASC-US; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (HSIL) (ASC-H); low-grade squamous intraepithelial lesion (LSIL); HSIL, favor AIN2 (HSIL-AIN2); and HSIL-AIN3. ASC-H, HSIL-AIN2, and HSIL-AIN3 were combined into a single high-grade cytology category for the current analysis. Biomarker Testing Using the residual specimen from the first collection, mtm Laboratories AG (Heidelberg, Germany) performed the p16INK4a/Ki-67 dual immunostaining (‘‘p16/Ki-67 staining’’) using their CINtec Plus cytology kit according to their specifications. A ThinPrep 2000 processor (Holo- gic) was used to prepare a slide, which then was stained according to the manufacturer’s instructions. The CINtec Plus cytology kit was then applied to the unstained cytol- ogy slide for p16/Ki-67 staining. On the second collected specimen, Roche Molecular Systems (Pleasanton, Calif) tested for HR-HPV, includ- ing separate detection of HPV-16, and HPV-18 DNA, using their cobas 4800 HPV test. To prepare DNA for the cobas test, automated sample extraction was per- formed as follows: 500 lL of the PreservCyt specimen was pipetted into a secondary tube (Falcon 5-mL polypropyl- ene round-bottom tube, which measured 12-mm-by-75- mm and was nonpyrogenic and sterile). The tube was capped, mixed by vortexing, uncapped, placed on the x-480 specimen rack, and loaded onto the x-480 sample extraction module of the cobas 4800 system. The x-480 extraction module then inputs 400 lL of this material into the specimen preparation process. The extracted DNA was then tested as previously described.16 NorChip AS (Klokkarstua, Norway) also tested the second specimen for XXX-00, -00, -00, -00, xxx -00 XXX X0/X0 mRNA using their PreTect HPV-Proofer assay according to their specifications. All testing was per- formed masked to the results of the other assays, clinical outcomes, and patient characteristics.

Study Population. The study was based at the San Francisco KPNC Anal Cancer Screening Clinic. We enrolled men who were identified as positive for HIV through the Kaiser HIV registry, who were aged ≥ 18 years, who were not diag- nosed with anal cancer before enrollment, and who pro- vided informed consent. In total, 363 men were enrolled between August 2009 and June 2010. The study was reviewed and approved by the institutional review boards at KPNC and at the National Cancer Institute. All partici- pants were asked to complete a self-administered ques- tionnaire to collect risk factor information. Additional information regarding HIV status and medication, sexu- ally transmitted diseases, and histopathology results were abstracted from the KPNC clinical database. For 87 of the 271 subjects without biopsy-proven AIN2 or AIN3 at the time of enrollment, follow-up infor- mation concerning outcomes from additional clinic visits up to December 2011 was available and included in the analysis to correct for the possible imperfect sensitivity of high-resolution anoscopy (HRA).13,15 Clinical Examination, Evaluation, and Results During the clinical examination, 2 specimens were col- lected by inserting a wet flocked nylon swab16 into the anal canal up to the distal rectal vault and withdrawing with rotation and lateral pressure. Both specimens were trans- ferred to PreservCyt medium (Hologic, Bedford, Mass). A third specimen was collected for routine testing for Chla- mydia trachomatis and Neisseria gonorrhea. After specimen collection, participants underwent a digital anorectal ex- amination followed by HRA. All lesions that appeared sus- picious on HRA were biopsied and sent for routine histopathological review by KPNC pathologists, and were subsequently graded as condyloma or AIN1 through AIN3. No cancers were observed in this study population. From the first specimen, a ThinPrep slide (Hologic) was prepared for routine Xxxxxxxxxxxx staining and xxxxx- xxxxx. Two pathologists (T.D. and D.T.) reviewed the slides independently. Cytology results were reported anal- ogous to the Bethesda classification17 for cervical cytology except when otherwise noted. The following categories were used: negative for intraepithelial lesion or malig- xxxxx (NILM); ASC-US; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (HSIL) (ASC-H); low-grade squamous intraepithelial lesion (LSIL); HSIL, favor AIN2 (HSIL-AIN2); and HSIL-AIN3. ASC-H, HSIL-AIN2, and HSIL-AIN3 were combined into a single high-grade cytology category for the current analysis. Biomarker Testing Using the residual specimen from the first collection, mtm Laboratories AG (Heidelberg, Germany) performed the p16INK4a/Ki-67 dual immunostaining (‘‘p16/Ki-67 staining’’) using their CINtec Plus cytology kit according to their specifications. A ThinPrep 2000 processor (Holo- gic) was used to prepare a slide, which then was stained according to the manufacturer’s instructions. The CINtec Plus cytology kit was then applied to the unstained cytol- ogy slide for p16/Ki-67 staining. On the second collected specimen, Roche Molecular Systems (Pleasanton, Calif) tested for HR-HPV, includ- ing separate detection of HPV-16, and HPV-18 DNA, using their cobas 4800 HPV test. To prepare DNA for the cobas test, automated sample extraction was per- formed as follows: 500 lL of the PreservCyt specimen was pipetted into a secondary tube (Falcon 5-mL polypropyl- ene round-bottom tube, which measured 12-mm-by-75- mm and was nonpyrogenic and sterile). The tube was capped, mixed by vortexing, uncapped, placed on the x-480 specimen rack, and loaded onto the x-480 sample extraction module of the cobas 4800 system. The x-480 extraction module then inputs 400 lL of this material into the specimen preparation process. The extracted DNA was then tested as previously described.16 NorChip AS (Klokkarstua, Norway) also tested the second specimen for XXX-00HPV-16, -00-18, -00-31, -00-33, xxx -00 XXX X0and -45 HPV E6/X0 E7 mRNA using their PreTect HPV-Proofer assay according to their specifications. All testing was per- formed masked to the results of the other assays, clinical outcomes, and patient characteristics.

Study Population. NIH-PA Author Manuscript The study was based at the San Francisco KPNC Xxxxxxxxx Xxxxxx Permanente Northern California (KPNC) Anal Cancer Screening Clinic. We enrolled men who were identified as HIV-positive for HIV through the Kaiser HIV registry, who were aged ≥ 18 yearsyears or older, who were not diag- nosed diagnosed with anal cancer before enrollment, prior to enrollment and who pro- vided provided informed consent. In total, 363 men were enrolled between August 2009 and June 2010. The study was reviewed and approved by the institutional review boards at KPNC and at the National Cancer InstituteNCI. All partici- pants participants were asked to complete a self-administered ques- tionnaire questionnaire to collect risk factor information. Additional information regarding on HIV status and medication, sexu- ally sexually transmitted diseases, and histopathology results were abstracted from the KPNC clinical database. For 87 subjects of the 271 subjects without biopsy-proven AIN2 or AIN3 at the time of enrollmentenrollment visit, follow-follow- up infor- mation concerning information on outcomes from additional clinic visits up to December 2011 12/2011 was available and included in the analysis to correct for the possible imperfect sensitivity of high-resolution anoscopy (HRA).13,15 13;15). NIH-PA Author Manuscript Xxxxxxx et al. Page 3 Clinical Examinationexam, Evaluationevaluation, and Results results During the clinical examination, 2 two specimens were col- lected collected by inserting a wet wetted flocked nylon swab16 swab (16) into the anal canal up to the distal rectal vault and withdrawing with rotation and lateral pressure. Both specimens were trans- ferred transferred to PreservCyt medium (Hologic, Bedford, MassMA). A third specimen was collected for routine testing for Chla- mydia trachomatis Chlamydia Trachomatis and Neisseria gonorrheaGonorrhea testing. After specimen collection, participants underwent received a digital anorectal ex- amination exam followed by high-resolution anoscopy (HRA). All suspicious-appearing lesions that appeared sus- picious on in HRA were biopsied and sent for routine histopathological review by KPNC pathologists, and were subsequently which was graded as condyloma or AIN1 through AIN3condyloma, and AIN 1-3. No cancers were observed in this study population. From the first specimen, a ThinPrep slide (Hologic) was prepared for routine Xxxxxxxxxxxx staining and xxxxx- xxxxx. Two pathologists (T.D. and D.T.) reviewed the slides independently. Cytology results were reported anal- ogous to the Bethesda classification17 for cervical cytology except when otherwise noted. The following categories were used: negative for intraepithelial lesion or malig- xxxxx (NILM); ASC-US; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (HSIL) (ASC-H); low-grade squamous intraepithelial lesion (LSIL); HSIL, favor AIN2 (HSIL-AIN2); and HSIL-AIN3. ASC-H, HSIL-AIN2, and HSIL-AIN3 were combined into a single high-grade cytology category for the current analysis. Biomarker Testing Using the residual specimen from the first collection, mtm Laboratories AG (Heidelberg, Germany) performed the p16INK4a/Ki-67 dual immunostaining (‘‘p16/Ki-67 staining’’) using their CINtec Plus cytology kit according to their specifications. A ThinPrep 2000 processor (Holo- gic) was used to prepare a slide, which then was stained according to the manufacturer’s instructions. The CINtec Plus cytology kit was then applied to the unstained cytol- ogy slide for p16/Ki-67 staining. On the second collected specimen, Roche Molecular Systems (Pleasanton, Calif) tested for HR-HPV, includ- ing separate detection of HPV-16, and HPV-18 DNA, using their cobas 4800 HPV test. To prepare DNA for the cobas test, automated sample extraction was per- formed as follows: 500 lL of the PreservCyt specimen was pipetted into a secondary tube (Falcon 5-mL polypropyl- ene round-bottom tube, which measured 12-mm-by-75- mm and was nonpyrogenic and sterile). The tube was capped, mixed by vortexing, uncapped, placed on the x-480 specimen rack, and loaded onto the x-480 sample extraction module of the cobas 4800 system. The x-480 extraction module then inputs 400 lL of this material into the specimen preparation process. The extracted DNA was then tested as previously described.16 NorChip AS (Klokkarstua, Norway) also tested the second specimen for XXX-00, -00, -00, -00, xxx -00 XXX X0/X0 mRNA using their PreTect HPV-Proofer assay according to their specifications. All testing was per- formed masked to the results of the other assays, clinical outcomes, and patient characteristics.

Study Population. The study was based at the San Francisco KPNC Anal Cancer Screening Clinic. We enrolled men who were identified as positive for HIV through the Kaiser HIV registry, who were aged ≥ ≤ 18 years, who were not diag- nosed with anal cancer before enrollment, and who pro- vided informed consent. In total, 363 men were enrolled between August 2009 and June 2010. The study was reviewed and approved by the institutional review boards at KPNC and at the National Cancer Institute. All partici- pants were asked to complete a self-administered ques- tionnaire to collect risk factor information. Additional information regarding HIV status and medication, sexu- ally transmitted diseases, and histopathology results were abstracted from the KPNC clinical database. For 87 of the 271 subjects without biopsy-proven AIN2 or AIN3 at the time of enrollment, follow-up infor- mation concerning outcomes from additional clinic visits up to December 2011 was available and included in the analysis to correct for the possible imperfect sensitivity of high-resolution anoscopy (HRA).13,15 Clinical Examination, Evaluation, and Results During the clinical examination, 2 specimens were col- lected by inserting a wet flocked nylon swab16 into the anal canal up to the distal rectal vault and withdrawing with rotation and lateral pressure. Both specimens were trans- ferred to PreservCyt medium (Hologic, Bedford, Mass). A third specimen was collected for routine testing for Chla- mydia trachomatis and Neisseria gonorrhea. After specimen collection, participants underwent a digital anorectal ex- amination followed by HRA. All lesions that appeared sus- picious on HRA were biopsied and sent for routine histopathological review by KPNC pathologists, and were subsequently graded as condyloma or AIN1 through AIN3. No cancers were observed in this study population. From the first specimen, a ThinPrep slide (Hologic) was prepared for routine Xxxxxxxxxxxx staining and xxxxx- xxxxx. Two pathologists (T.D. and D.T.) reviewed the slides independently. Cytology results were reported anal- ogous to the Bethesda classification17 for cervical cytology except when otherwise noted. The following categories were used: negative for intraepithelial lesion or malig- xxxxx (NILM); ASC-US; atypical squamous cells cannot rule out high-grade squamous intraepithelial lesion (HSIL) (ASC-H); low-grade squamous intraepithelial lesion (LSIL); HSIL, favor AIN2 (HSIL-AIN2); and HSIL-AIN3. ASC-H, HSIL-AIN2, and HSIL-AIN3 were combined into a single high-grade cytology category for the current analysis. Biomarker Testing Using the residual specimen from the first collection, mtm Laboratories AG (Heidelberg, Germany) performed the p16INK4a/Ki-67 dual immunostaining (‘‘p16/Ki-67 staining’’) using their CINtec Plus cytology kit according to their specifications. A ThinPrep 2000 processor (Holo- gic) was used to prepare a slide, which then was stained according to the manufacturer’s instructions. The CINtec Plus cytology kit was then applied to the unstained cytol- ogy slide for p16/Ki-67 staining. On the second collected specimen, Roche Molecular Systems (Pleasanton, Calif) tested for HR-HPV, includ- ing separate detection of HPV-16, and HPV-18 DNA, using their cobas 4800 HPV test. To prepare DNA for the cobas test, automated sample extraction was per- formed as follows: 500 lL of the PreservCyt specimen was pipetted into a secondary tube (Falcon 5-mL polypropyl- ene round-bottom tube, which measured 12-mm-by-75- mm and was nonpyrogenic and sterile). The tube was capped, mixed by vortexing, uncapped, placed on the x-480 specimen rack, and loaded onto the x-480 sample extraction module of the cobas 4800 system. The x-480 extraction module then inputs 400 lL of this material into the specimen preparation process. The extracted DNA was then tested as previously described.16 NorChip AS (Klokkarstua, Norway) also tested the second specimen for XXX-00HPV-16, -00-18, -00-31, -00-33, xxx -00 XXX X0and -45 HPV E6/X0 E7 mRNA using their PreTect HPV-Proofer assay according to their specifications. All testing was per- formed masked to the results of the other assays, clinical outcomes, and patient characteristics.