Overview

Designed as a fundamental, compact instrument with user friendly features and characteristics, the CD Ratiometer optically assesses the scanned tissue only at pre-established optical wavelengths. Moreover, it instantaneously reports out a "yes", "no", or "maybe" result viewed on a CRT screen.

Assuredly, the CD Ratiometer, with its assortment of disposable probe designs, will be the preferred product for medical practitioners to use in the office or clinical setting.

Clinical Validation-Pilot Study

• IDE submission December 2005
• Goals of Pilot Study
  – Optical spectroscopy to define specific state of tissues
  – Emission from tissues provide information for cancer and pre cancer
• Clinical documentation to support safety and efficacy
• To confirm sensitivity and specificity; significantly improved outcomes versus the standard (i.e., Pap smear)

Diagnostic Device

Current Prototype	Future Packaged Device

• Dual channel detector
• Algorithms based on intensity ratios
• Multiple wavelength pairs
• Fast data acquisition (< 2 sec/ ratio)
• Probes - Free standing, adapts to endoscopes, colposcopes, fiber needles

Market Size

• 190,000 deaths annually worldwide
• 371,000 new cases each year
• 3,410 deaths annually in U.S.
• 10,370 new cases annually in U.S.
• 27% of all cancer in African women
• 18% of all cancer in South American and Indian women
• 55 million Pap smears annually in the U.S. and Europe
• Two million Colposcope exams annually in the U.S. and Europe

The Worldwide market for Cervical Cancer diagnostics in constant dollars is in excess of $1.5 Billion.

Features and Benefits

• 25 Patents covering cancer detection and tissue spectroscopy
• Real-time results – CD-R provides a non-invasive, real-time, point-of-care diagnosis during an annual routine gynecological exam
• Reduced sampling errors
• No pain or bleeding
• Reimbursement anticipated
• Proprietary algorithms collect the maximum range of diagnostic information available
• System is module and will contain a disposable sheath
• Increased accuracy – CD-R has displayed sensitivity and specificity equal or greater than 95% in laboratory tests

HPV Vaccines and Development of the
Optical Biopsy CD-Ratiometer

Every year, more than 500,000 cancers of the cervix are diagnosed worldwide. Between 30% and 40% of cervical cancer patients die from their disease. Every year, 1,800,000 to 2,000,000 patients will be diagnosed with severe precancerous cervical lesions (350,000 in the U.S. alone), 50 to 75 million will be diagnosed with minor precancerous lesions (1.1 to 1.6 million in the U.S. alone). HPV related conditions cost this country $4-6 billion in medical costs. These statistics will likely continue to increase for the foreseeable future. In the U.S., 20-25 million people are infected with HPV. The incidence of HPV will continue to increase until large segments of the population at risk is routinely vaccinated. Only then will the incidence and prevalence of HPV infections start to decreased. This will take several years.

Recently, there have been two major technological breakthroughs in the fight against HPV and cervical cancer. The first breakthrough is the development of "Optical Biopsy" - a light based method to screen for cervical cancer and pre-cancer. Optical Biopsy was developed at the Institute for Ultrafast Spectroscopy and Lasers (IUSL) at The City College of New York, under the leadership of Prof. R. R. Alfano, director of the IUSL. Mediscience Technology Corp is funding the development of an Optical Biopsy instrument, named the Cancer Diagnosis (CD)-Ratiometer at the IUSL. The other major breakthrough is the announcements of development of HPV vaccines by Merck and Glaxo. These two technologies, screening and vaccination, are not in conflict but are complimentary - each providing a tool to fight cervical cancer.

The war on HPV must be viewed in terms of two different target populations. One target population is composed of those who have not been infected with HPV, but are at risk for infection. This population is in need of prevention. The second population consists of those already infected with HPV and those who will become infected (subjects for whom prevention failed or not yet available). This population is in need of continual screening, diagnosis, treatment and post-treatment monitoring.

For the first group, vaccination is the most important part of the solution. However there are many issues which may take significant time to be resolved (i.e. efficiency of the vaccines, need for repeated boosters, duration of immunization, failure to provide immunization, emergence of new strains of viruses, etc). Although Merck vaccine was just approved last week (June6th, 2006) many problems will need to be resolved. Short studies show that the vaccine is not fool proof and that it only targets two carcinogenic strains of HPV (HPV 16 and 18) out of ~35 sexually transmitted strains of the virus. HPV 16, 18, 6 and 11 combined are responsible for 2/3 of cervical cancer and pre-cancer cases. The other 33 strains as well as other potential but unknown factors, which are not prevented by the vaccine, are responsible for the other 1/3 of the cases. The Glaxo vaccine (Cervarix) faces problems similar to Gardasil. In addition to issues of effectiveness, widespread distribution, HPV vaccines will face additional hurdles. These include: cost factors, religious objections, politics and patent issues, populations selection. It may take many years to vaccinate a significant fraction of the world population at risk. Additionally, besides the FDA, Merck insists that despite the favorable results obtained with their vaccine, patients MUST BE FOLLOWED WITH PAP SMEARS REGULARLY and INDEFINITELY. Vaccination against HPV 16/18 and 6/11confers no protection against any of the others 33 strains of sexually transmitted HPV and a fortiori those cases where other factors are responsible for pre-cancer and cancer. The vaccines will apply best only to not yet sexually active target population ? 15 year of age. For older patients, selection criteria will be a significant issue.

For the second population group (those infected with HPV), patients will need to be screened, diagnosed, treated and/or monitored after treatment for a period of 15 to 25 years (from age 18 to age 40/45). During this period, the CD-Ratiometer can provide an efficient, cost effective, screening tool with all the advantages of Optical Biopsy (no need to remove tissue, real-time results, and high accuracy).

In summary, cervical screening using Mediscience Technology's Optical Biopsy fluorescence technology will help women for the foreseeable future in the fight against cancer.

Dr. S. Lubicz, M.D. Gynecologist and Oncologist, Consultant to Mediscience Technology

Prof. R. R. Alfano, Ph.D. Distinguished Professor of Science and Engineering, the City University of New York, Consultant to Mediscience Technology

Dr. A. Katz, Ph.D. Senior Research Staff, Institute for Ultrafast Spectroscopy and Lasers at the City College of New York

From the New England Journal of Medicince
The Potential of Human Papillomavirus Vaccines

Robert Steinbrook, M.D.

March 16, 2006

The anticipated licensure within the next three months of a vaccine against human papillomavirus (HPV) would represent a major public health advance against cervical cancer and other, less common cancers, including those of the anus, penis, vagina, and vulva. The Food and Drug Administration (FDA) is conducting a six-month priority review of Merck's investigational HPV vaccine and should announce its licensing decision by June 8. Questions remain, however, about the potential behavioral consequences of routinely vaccinating adolescents against a sexually acquired infection, and the public reaction is uncertain.

Genital HPV infection is common, with an estimated 6.2 million new infections each year in the United States. Although most infections are asymptomatic and transient, persistent infection with oncogenic HPV types is a serious health issue. Cervical cancer is the 11th most common cancer among women in the United States — with an estimated 10,370 new cases and 3710 deaths in 2005. There are racial and socioeconomic disparities; more than half of all cases occur in women who have never or rarely been screened. Among women in developing countries, where effective screening programs are often lacking (see page 1110), cervical cancer is the second most common cancer, and a leading cause of cancer-related death.

The two investigational HPV vaccines are based on technology invented at the National Institutes of Health and licensed for commercial development.1,2 Merck has made a quadrivalent vaccine for use in men and women that is administered in three doses (at 0, 2, and 6 months). A key reason for vaccinating men is to prevent them from transmitting HPV to women or to other men. The vaccine is designed to protect against HPV types 16 and 18, which are responsible for an estimated 70 percent of cases of cervical, anal, and genital cancers, and HPV types 6 and 11, which cause an estimated 90 percent of cases of genital warts. The latter two types also cause an estimated 90 percent of cases of recurrent respiratory papillomatosis, a rare but debilitating disease that can occur in infants as well as adults, in which papillomas obstruct the airway; patients may require many surgical procedures to remove the obstructions.

GlaxoSmithKline is testing, for use in women, a bivalent vaccine against HPV types 16 and 18 that is also administered in three doses (at 0, 1, and 6 months). Both vaccines consist of papillomavirus-like particles, which are empty shells of viral structural proteins. They are thought to protect against HPV infection primarily by inducing the production of neutralizing antibodies, thereby preventing the development of cervical intraepithelial neoplasia — the precursor lesion of invasive cervical carcinoma — and other precancerous lesions.

HPV vaccines will not prevent infection with other sexually transmitted diseases, nor will their introduction eliminate the need for cervical-cancer screening; screening will continue to be essential to detect cancers and precancerous changes caused by other HPV types, as well as any cancer in women who have not been vaccinated or are already infected with HPV. If the vaccines' promise is fulfilled, however, they will markedly reduce the need for medical care, biopsies, and invasive procedures associated with the follow-up of abnormal Pap tests, as well as alleviating the associated anxieties and health care costs.

The pivotal efficacy and safety data for the HPV vaccines remain unpublished, and some are still being collected, particularly for the GlaxoSmithKline vaccine. Nonetheless, the data presented by the companies in public meetings of the federal Advisory Committee on Immunization Practices (ACIP) show that the vaccines have a high degree of efficacy and that the immune response is strongest in persons who are vaccinated at younger ages. The Merck vaccine has high efficacy against cervical intraepithelial neoplasia and external genital lesions in women 16 to 26 years of age, according to Lauri Markowitz of the Centers for Disease Control and Prevention (CDC), who reviewed the data for the committee. The Merck vaccine has remained effective for 2.5 to 3.5 years after a three-dose series, and it appears to be safe, the main adverse reaction being pain at the injection site.

After the companies' February presentations to the ACIP, Jon Abramson, chairman of the committee, said in an interview that he "had never before seen vaccines that in the prelicensure studies have close to 100 percent efficacy. The data are absolutely stunning." Abramson, who also chairs the department of pediatrics at the Wake Forest University School of Medicine, added: "The problem is that we don't know how long the protection will last. The worst that should happen is that a booster vaccine will be needed."

In December 2005, Merck submitted to the FDA an application for a biologics license for its HPV vaccine. The application covers the vaccination of girls and boys 9 to 15 years of age and of women 16 to 26 years of age. The FDA is expected to set the age range for the vaccine and decide whether it will be licensed for use in boys as well as girls and women. Although Merck has not revealed the price it intends to charge for a three-dose series, a company cost-effectiveness analysis assumes a cost of $300 to $500, according to a presentation to the ACIP. GlaxoSmithKline is expected to submit its licensing application to the FDA before the end of 2006.

The ACIP plays a critical role in advising the CDC and the Department of Health and Human Services about the use of vaccines, and the government usually follows its recommendations. The committee is also influential in determining which vaccines will be paid for by state and federal programs and private insurance companies.

If Merck's HPV vaccine is licensed, the ACIP will probably vote at a June meeting on whether to recommend routine vaccination at 11 to 12 years of age, in an effort to confer immunity before adolescents become sexually active. HPV infection is usually acquired soon after sexual activity begins, with a cumulative incidence of about 40 percent within 16 months. According to 2003 data from the Youth Risk Behavior Surveillance System, 7.4 percent of adolescents initiate sexual activity before 13 years of age, about one third of them by ninth grade, and about two thirds by the end of high school. If people are vaccinated before they have had sex, they should benefit irrespective of when they become sexually active.

The ACIP may also decide whether the vaccine should be recommended for older adolescents and young adults who have not been previously vaccinated and — depending on the FDA's licensing criteria — whether it should be recommended for boys as well as girls and women. Although a recommendation for routine HPV vaccination should lead to widespread use, it would be substantially different from mandating vaccination. According to Abramson, the committee is not considering the latter approach, nor does it have authority to make such recommendations. Mandating vaccination requires action by individual states.

In addition to the outcome of the FDA review, there are many unknowns about HPV vaccination. One is the duration of immunity, which will have to be determined through follow-up studies. Another is the effect on sexual behavior, which should be learned through monitoring efforts. Nonetheless, Nicole Liddon, a sociologist at the CDC, told the committee in February that it is "unlikely" that routine HPV vaccination will change adolescent sexual behavior: the initiation of sexual activity reflects many factors, including parental and community influences; fear of sexually transmitted diseases has not been a major motivation for adolescents to abstain from sex; and the availability of condoms and emergency contraception has not had measurable effects on the frequency of unsafe behavior.

The acceptance of the HPV vaccine — by physicians, parents, preteens, and the public at large — is also uncertain. As with many issues related to sex, people may have strong views. Increased acceptance is likely to require ongoing discussion and educational efforts. At the February ACIP meeting, the conservative Family Research Council, which promotes abstinence before marriage and fidelity within marriage as the best way to prevent sexually transmitted diseases, distanced itself from suggestions that it opposed HPV vaccines.3 Calling such reports "false," the council said it "would oppose any measures to legally require vaccination or to coerce parents into authorizing it" and that "there is no justification for any vaccination mandate as a condition of public school attendance. However, we do support the widespread distribution and use of vaccines against HPV."

Finally, the epidemiology of cervical cancer highlights the need to provide HPV vaccines to persons who may never or rarely be screened, as well as to improve cervical-cancer prevention programs so that they will reach the women with the highest risk of disease.4,5 The HPV vaccine is likely to be considerably more expensive than many recommended vaccines, and its benefits will not be fully apparent for decades. It will be far easier to recommend routine vaccination than to provide the resources for its routine use, in the United States and throughout the world.

Source Information

Dr. Steinbrook is a national correspondent for the Journal.

An interview with Dr. Douglas Lowy, chief of the Laboratory of Cellular Oncology at the National Cancer Institute, can be heard at www.nejm.org.

References

1. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a human papillomavirus type 16 vaccine. N Engl J Med 2002;347:1645-1651.

2.Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364:1757-1765.

3.Goodman E. Good news on cancer? Not for everyone. Boston Globe. November 12, 2005:A11.

4.Blumenthal PD, Gaffikin L. Cervical cancer prevention making programs more appropriate and pragmatic. JAMA 2005;294:2225-2228.

5.Schiffman M, Castle PE. The promise of global cervical-cancer prevention. N Engl J Med 2005;353:2101-2104.