Potential Clinical Utility of Performing HPV Genotyping Test Featured in Study Reported in Journal of the National Cancer Institute; New Study Uses Roche Diagnostics' Test to Detect High-Risk Types of Human Papillomavirus.

PLEASANTON, Calif. -- Roche Diagnostics announced today that the results of the ALTS (ASCUS/LSIL Triage Study for Cervical Cancer) clinical trial, which were published in the July 20, 2005 issue of the Journal of the National Cancer Institute (JNCI),(1) support the use of genotyping certain human papillomavirus (HPV) high-risk types (particularly HPV16). HPV genotyping may be important to assessing the risk of developing pre-cancerous conditions or cervical cancer in women with either ASCUS (an ambiguous type of cellular abnormality formally called "atypical squamous cells of undetermined significance") or LSIL (mildly abnormal cells formally called "low-grade squamous intraepithelial lesions") results of Pap testing.

According to Chris Meda, Vice President of Women's Health at Roche Molecular Diagnostics, a business area of Roche Diagnostics, "We are proud to have furnished research reagents that led to providing genotyping information for this landmark study. Roche Diagnostics has a new Linear Array HPV Genotyping Test, which has received CE Mark certification for in vitro diagnostic use in the European Union and includes both the low- and high-risk genotypes. We are dedicated to improving women's health through continuing Roche Diagnostics' legacy of innovation in PCR technology."

Evaluating the risk of individual women with ASCUS and LSIL findings in Pap testing is important because some of the abnormalities resolve in the absence of treatment, whereas others may progress to a pre-cancerous condition or cervical cancer. The National Cancer Institute (NCI)-sponsored ALTS study of 5,060 women who had either ASCUS or LSIL results on Pap testing utilized several types of assays, including Roche Diagnostics' polymerase chain reaction (PCR) and nucleic acid hybridization-based research reagents for the HPV line blot test, an earlier, prototype version of Roche Diagnostics' new Linear Array HPV Genotyping Test (CE IVD)(2), to detect the presence of both high- and low-risk genotypes of HPV.

"The ALTS study concluded that ASCUS and LSIL patients who have a positive HPV16 diagnosis by genotyping are at significantly greater risk for detection of high-grade abnormalities during a 2-year follow-up period when compared to those who test positive for another oncogenic type of HPV or who are HPV-negative," commented Cosette Wheeler, Ph.D., Professor at the University of New Mexico School of Medicine, a co-author of the study. "Given these results, the potential benefits of risk stratification via HPV genotyping warrants further clinical, technical, and cost-effectiveness analyses."

Persistent infections with high-risk genotypes of HPV (such as HPV16) are believed to be the cause of virtually all cervical cancers and the precursor condition, cervical intraepithelial neoplasia grade 3 (CIN3).(2) Roche Diagnostics' HPV line blot test was used to identify up to 37 high- and low-risk genotypes in samples taken from patients at study entry. For the ALTS clinical trial, HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 were considered the primary oncogenic (i.e., cancer-causing) types of HPV to be analyzed.

About Roche and the Roche Diagnostics Division

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As a supplier of innovative products and services for the early detection, prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is a world leader in diagnostics, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2004, sales by the Pharmaceuticals Division totaled 21.7 billion Swiss francs, while the Diagnostics Division posted sales of 7.8 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

Roche's Diagnostics Division offers a uniquely broad product portfolio and supplies a wide array of innovative testing products and services to researchers, physicians, patients, hospitals and laboratories worldwide. For further information, please visit our websites, www.roche.com and www.roche-diagnostics.com.

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Backgrounder

In the ALTS study, women with ASCUS or LSIL Pap test results and who tested positive for HPV16 in the Roche Diagnostics' HPV Line Blot test had 38 times the risk of developing CIN3 or cervical cancer within 2 years, compared to HPV-negative women in the study. Women who tested positive for other oncogenic types of HPV in Roche Diagnostics' Line Blot test had 7 times the risk of developing CIN3 or cervical cancer within 2 years, compared to HPV-negative women in the study.

Women in the study were treated with three different management strategies. Some women were treated immediately with colposcopy (a special examination that may involve biopsy) regardless of their Pap test results, whereas other women were treated with colposcopy if they were HPV- high risk genotype positive or if they exhibited HSIL (high-grade squamous intraepithelial lesions). All patients were followed with further testing and colposcopy at the end of 2 years to determine whether their disease state progressed to pre-cancerous or cancerous conditions of the cervix. Women whose test results progressed to cervical intraepithelial neoplasia grade 2 (CIN2) or higher received additional treatment.

About Cervical Cancer Screening and HPV

According to the World Health Organization (WHO), cervical cancer is the second most common cause of cancer mortality in women globally. Every year, approximately 471,000 women worldwide develop cervical cancer, and an estimated 233,000 die due to the disease. In the total absence of screening programs (routine Pap smear) in developing countries, cervical cancer is detected too late and leads to death in almost all cases. Even with Pap screening programs, a significant number of women in developed countries die of cervical cancer. For example, in the U.S., approximately 13,000 new cases of cervical cancer are diagnosed each year, and an estimated 4,000 women die of the disease. In Western and Eastern Europe, approximately 48,000 new cases of cervical cancer are diagnosed annually, and an estimated 21,000 women die of the disease.(3)

Almost all (99.8%) cervical cancers are caused by specific types of a sexually transmitted DNA tumor virus called human papillomavirus (HPV).(3)(4) To screen for cervical cancer, 160 million Pap tests are performed worldwide each year. Through the approval of reimbursement initiatives for HPV screening, governments around the world now are recognizing the importance of HPV screening in preventing cervical cancer.

(1)Castle PE, Solomon D, Schiffman M, and Wheeler CM for the ALTS Group. Human papillomavirus type 16 infections and 2-year absolute risk of cervical precancer in women with equivocal or mild cytologic abnormalities. J Nat Can Inst. 2005; 97(14):1066-1071.

(2)CE Mark Certification (Conformite' Europeene); not available in the US.

(3)Ferlay J, Bray F, Pisani P, and Parkin DM. GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0, IARC CancerBase No. 5. Lyon: IARC Press, 2001.

(4)Walboomers JMM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189:12-19.