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Cervista™ HPV HR 95-438 PRD-00804

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Cervista™ HPV HR 95-438 PRD-00804 Cervista™ Cervista™ HPV HR 95-438 PRD-00804 An in vitro diagnostic test for the detection of DNA from14 high-risk Human Papillomavirus (HPV) types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in Cervical Specimens. -15°C 95-438: -30°C PRD-00804: Do NOT store in frost-free freezer. Protect from light. Table of Contents General Information .......................................................................................................................... 2 Abbreviations Used ........................................................................................................................... 3 Summary and Explanation of the Test ............................................................................................. 3 Principles of the Procedure .............................................................................................................. 4 Reagents Provided ............................................................................................................................ 5 Warnings and Precautions ............................................................................................................... 6 Reagent Storage and Handling Requirements ................................................................................ 6 Additional Reagents and Materials .................................................................................................. 6 Materials Required, But Not Provided, for Manual Testing ............................................................ 6 Materials Required, But Not Provided, for Automated Testing ...................................................... 7 Specimen Collection and Storage for Analysis ............................................................................... 7 Automated Test Procedure for the Cervista HTA System ............................................................... 7 Manual Test Procedure for Cervista HPV HR .................................................................................. 7 Procedural Notes and Precautions .................................................................................................. 9 Interpretation of Results ................................................................................................................... 9 Quality Control ................................................................................................................................ 11 Limitations ....................................................................................................................................... 12 Expected Results............................................................................................................................. 13 Performance Characteristics .......................................................................................................... 14 Test Performance Characteristics Using the Cervista HTA System ............................................ 27 Troubleshooting .............................................................................................................................. 31 Bibliography .................................................................................................................................... 36 Contact Information: ....................................................................................................................... 37 Invader™ Cervista™ General Information Intended Use The Cervista HPV HR test is an in vitro diagnostic test for the qualitative detection of DNA from 14 high-risk Human Papillomavirus (HPV) types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in cervical specimens. The Cervista HPV HR test cannot determine the specific HPV type present. The Cervista HPV HR test uses the Invader™ chemistry, a signal amplification method for detection of specific nucleic acid sequences. This method uses two types of isothermal reactions: a primary reaction that occurs on the targeted DNA sequence and a secondary reaction that produces a fluorescent signal. The Cervista HPV HR test is indicated: 1) To screen patients with atypical squamous cells of undetermined significance (ASC-US) cervical cytology results to determine the need for referral to colposcopy. 2) In women 30 years and older the Cervista HPV HR test can be used with cervical cytology to adjunctively screen to assess the presence or absence of high-risk HPV types. This information, together with the physician’s assessment of cytology history, other risk factors, and professional guidelines, may be used to guide patient management. Cervical specimens that may be tested with the Cervista HPV HR test include the following preservation system collection media and collection devices: • ThinPrep™ Pap Test PreservCyt™ Solution • Broom-type device (e.g., Rovers Cervex® Brush, Wallach Papette®), or Endocervical Brush/Spatula The Cervista HPV HR test may be performed either manually or using the automated Cervista High Throughput Automation (HTA) system. Warnings • The Cervista HPV HR test is not intended for use as a screening device for women under age 30 with normal cervical cytology. • The Cervista HPV HR test is not intended to substitute for regular cervical cytology screening. • Detection of HPV using the Cervista HPV HR test does not differentiate HPV types and cannot evaluate persistence of any one type. • The use of this test has not been evaluated for the management of women with prior cytological or histological abnormalities, hysterectomy, who are pregnant, postmenopausal, or who have other risk factors (e.g., HIV+, immunocompromised, history of STI). • The Cervista HTA system is only to be used for Cervista HPV HR testing and cannot be utilized for testing with the Cervista HPV 16/18 test. • The Cervista HPV HR test is designed to enhance existing methods for the detection of cervical disease and should be used in conjunction with clinical information derived from other diagnostic and screening tests, physical examinations, and full medical history in accordance with appropriate patient management procedures. • Cervista HPV HR test results should not be used as the sole basis for clinical assessment and treatment of patients. Cervista HPV HR 2 15-3100, Rev. 105 Invader™ Cervista™ Abbreviations Used ASC-US: Atypical squamous cells of undetermined significance CIN: Cervical intraepithelial neoplasia CLSI Clinical and Laboratory Standards Institute DNA: Deoxyribonucleic acid FAM: Carboxyfluorescein dye Red: Redmond® red dye FRET: Fluorescence resonance energy transfer FOZ: Fold over zero (sample or control signal divided by No Target Control signal) gDNA: Genomic DNA HIST2H2BE: Human histone 2 gene, H2be gene HPV: Human papillomavirus HR: High-risk HTA High Throughput Automation LoB Limit of Blank LoD Limit of Detection Max. Maximum Min. Minimum NILM: Negative for intraepithelial lesion or malignancy. This category encompasses the previous categories of "within normal limits" and "benign cellular changes”. NTC: No target control Oligo: Oligonucleotide Pap: Papanicolaou cervical cytology test RFU: Relative fluorescence unit Summary and Explanation of the Test Over 100 HPV types have been documented in the literature, approximately 40 of which infect the anogenital area and are transmitted sexually. Anogenital HPV is associated with virtually all cancers of the cervix.1 Cervical cancer has previously been shown to be highly preventable when cytological and HPV screening programs are employed to facilitate the detection and treatment of pre-cancerous lesions. Of the sexually transmitted types of HPV, 14 oncogenic genotypes (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), are considered high-risk (HR) HPV types due to their strong association with cervical cancers (relative to low risk HPV types, which have little or no association with cervical cancer).2,3 Still, the vast majority of high-risk HPV infections are cleared.4 Very few high-risk HPV DNA positive women develop cytologic high-grade SIL (HSIL) indicating underlying CIN2-3 or cancer.5 The absolute risk of developing an incident cytologic abnormality following a HR HPV infection is known to vary in different populations. The presence of high-risk HPV DNA in conjunction with an equivocal or ambiguous cytology result (ASC-US) places a woman at increased risk for having an underlying cervical intraepithelial neoplasia 2 or 3 (CIN2 or CIN3).6,7,8 CIN3, while occurring in only approximately 5% of ASC-US cases,9 is an immediate precursor to cervical cancer and consequently its detection is very important for patient management.3 Therefore, the identification of those women with ASC-US cytology in conjunction with a high-risk HPV infection is a useful aid for clinicians to decide who should be monitored more aggressively.3,6,10,11 Current scientific literature suggests that persistent infection with high-risk HPV is the main risk factor for development of high-grade cervical neoplasia and cancer.4,12,13,14 Apparent persistence may represent continuous infection with a single HPV type, with multiple HPV types, or reinfection. Nonetheless, women with normal cervical cytology who are HR HPV negative appear to be at low risk for having or developing cervical precancerous lesions.15,16 Beginning in 2002, patient management guidelines have been published by various groups of U.S. healthcare professionals that recommend how women should be screened for cervical cancer according to age, the presence of cytological
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