Cervical cancer is the fourth most common cancer and cause of cancer mortality in women, worldwide (World Health Organization 2012/2013).
Cervical cancer is also the most common cancer in young women, aged <35 years.
Despite severe limitations in screening methods (see below), western countries have seen a decrease in cervical cancer-related mortality and an increase in the overall disease detection. However, in developing and third world countries, , cervical cancer is still a leading cause of death, accounting for over 275,000 annual deaths worldwide.
The Human Papilloma Virus (HPV) is the cause of virtually all (99%) cases of cervical cancer (intraepithelial neoplasia), when HPV16 & HPV18 cause ~70% of cancers.
Cervical cancer develops slowly, for 10-20 years, in the epithelium, a thin layer of cells which cover the cervix, typically in a specific area known as the “transitional zone”. Women will develop abnormalities and pre-cancerous changes in the cervix years before cancer development.
These pre-cancerous changes are described as being high-grade Cervical Intraepithelial Neoplasia (CIN). Women may also develop low-grade CIN, which is not considered pre-cancerous but can develop to be cancerous. Infection with certain genotypes of HPV has been shown to be associated with the development CIN, followed by progression to cervical cancer. However, most HPV infections will be cleared by the immune system and will not progress to CIN or cancer.
Cervical cancer is the number one cause of cancer-related death for women in the developed world. Out of BRIC countries, India is the leader in overall deaths, with nearly 73,000 annual deaths. China and Brazil follow closely.
Biop's system will be ideal for usage in developing countries as a "single point of care" screening method since these countries suffer from low numbers or lack of highly-trained gynaecologists and diagnostic labs.
More than 25 women out of 1,000 will die of cervical cancer. There are no organized screening programs.
20% of worldwide cervical cancer incidences are in sub-Saharan Africa or in India.
Bulletin of the World Health Organization
Cervical cancer screening is done increasingly via an HPV test, slowly replacing the past gold-standard test, the Pap smear. Nevertheless, HPV tests have a high false positive rate, as 80% of US adults will be infected with HPV at least once in their lifetime. 90% of these infections are cleared within 1-2 years (WebMD), and do not advance to cervical cancer.
As such, many women will receive positive HPV (and/or Pap) results, which leads to repeated tests and follow-up colposcopies, to ensure infection clearance. While most infections will clear, some women will develop a pre-cancerous condition, turning the ongoing testing period to a time fraught with fear of potential cervical cancer, even for the women in whom the infection will regress.
During a colposcopy test, the physician, or in some cases, a specialist or a gynaecological-oncologist, examines the vagina and the cervix via a colposcope, which is a lighted magnifying device. The physician searches these areas for lesions or other irregularities, which may be pre-cancerous or cancerous. In some cases, the physician uses acetic acid or iodine dies, to highlight suspicious areas. When deemed relevant, biopsy samples from suspicious areas are collected and inspected by an expert pathologist.
As cervical cancer advances slowly, the above screening method is likely to identify pre-cancerous lesions, if performed according to the recommendations of the medical community. Cervical cancer mortality rates decreased by 74% between 1955 and 1992 in the US due to increased screening and early detection using the Pap test (University of Maryland). Nevertheless, there are still many missed cases, and misdiagnosed patients in western countries and especially in developing countries.
While the above-described screening process and subsequent testing procedures improved early detection of cervical cancer, resulting in significantly lower mortality rates, there are several limitations to the current screening method. The Pap and HPV tests suffer from relatively high false positive and false negative rates. The Pap smear, for instance, suffers from a 10-20% false negative rate ( some studies quote the false-negative rate as high as 45%). This inaccuracy is usually attributed to imperfect sample collection, in which the infected area is missed or loss of some cells before they are transferred to the slide/tube, or as a result of a wrong diagnosis by the cytologist. Each Pap test requires review of multiple slides and numerous cells.
The HPV test suffers from a 10% false negative rate attributed to imperfect cell collection, or to infection by an HPV strain, which is not recognized by the HPV test.
Currently, colposcopy exams utilize acetic acid to visualize and identify suspicious areas, from which biopsies are taken. However, most physicians take multiple biopsies both from these abnormal areas, and randomly from all quadrants of the cervix, in order to improve the chances of identifying cancerous areas.
In the majority of cases , the results of the colposcopy and the subsequent biopsies are normal. These statistics suggest that many unnecessary biopsies are performed every year, which is a major issue, in light of the fact that biopsies are associated with discomfort, risk of infection, potential future fertility issues and delayed diagnosis, which causes the patient undue stress.
In the US, over 3 million Pap tests are found to be abnormal (~6% of all tests) annually. Of these only 12,000 are diagnosed as cancer, annually, imposing a great burden on the medical system