HPV OncoTect

HPV OncoTect is a method for screening cervical carcinoma identifying the oncogenic activity of Human papillomavirus (HPV) in infected cervical cells.
This method has been developed by Bruce K. Patterson, M.D in Stanford University School of Medicine (Department of Pathology) and is being researched in U.S.A, Canada, South Africa and Spain.
HPV and cervical cancer
HPV is one of the most common sexually transmitted infections and a necessary cause of cervical cancer.. HPV infection is highly transmissible, and most men and women acquire it at some time in their life.
More than 100 types of HPV have been identified which can be classified as high-risk or low-risk depending on their oncogenic activity. Infections with HPV take place in cervical epithelium and are usually of transient nature. Fortunately about 90% of HPV infections clear within two years without treatment. Only in a small amount of the women infected with oncogenic types of HPV, the infection will progress to high-grade lesions or even cervical cancer in the absence of treatment.
During persistent infections the viral genomes sometimes integrate into the host chromosome, assumedly causing an overexpression of the viral proteins E6 and E7, which increase the likelihood of immortalization and malignant transformation of the host cells.
Cervical cancer screening
Cervical cancer affects approximately 500,000 women worldwide. Cervical cancer screening programs have dramatically reduced the number of deaths and the prevalence of cervical cancer. Therefore screening programs are the main tool to prevent cervical cancer-associated mortality.
The Papanicoloau (Pap) smear has been the standard of care in the United States for over 40 years, resulting in a 74% decline in deaths due to cervical cancer. Despite this success, screening programs that rely on Pap-stained cytological samples have the limitations of relativity low sensitivity (30-87%) and a high false negative rate.
In women 30 years and older, the current HPV DNA test can be used for adjunctive screening with Pap smear to detect oncogenic types of HPV in cervical cytology specimens. Most HPV DNA assays such as type-specific polymerase chain reaction (PCR) and Hybrid Capture II (Digene) detect the present of HPV infection despite the fact that only a small proportion of the women infected with a high-oncogenic-risk type will suffer disease that progresses to cancer. Although HPV assays have a high sensitivity, their specificity is low because they detect an infection that in the vast majority of women do not develop cancer and regress spontaneously.
As persistent infection is a decisive factor for the progressive course of the disease, it may be important to identify a long term persistent infection. For that reason in the last years new molecular markers have been developed and there are new tests that identify cells with malignant transformation. One of these new tests is HPV OncoTect which used as an adjunct to the Pap test is a reliable screening technique to prevent cervical cancer. This method is highly sensitive and specific, with a high positive predictive value for detecting the presence of lesions with high probability of progression.
Despite the fact that continued expression of the E6 and E7 genes of oncogenic HPVs is the molecular switch for the development of cervical cancer, HPV OncoTect test quantify E6/E7 protein expression in cervical cells. The level of E6 and E7 gene expression is increased in high-grade lesions compared with low-grade lesions, making the level of E6 and E7 gene expression a functional discriminator between high-risk and low-risk infections.
How does HPV OncoTect work?
HPV OncoTect is a flow cytometry based in situ test for the detection of HPV E6 and E7 mRNA in intact ectocervical cells. HPV OncoTect takes advantage of the fact that oncogenic genotypes of HPV overexpress E6 and E7 mRNA following integration of HPV into genomic DNA.
Current investigations suggest that in situ detection of active viral mRNA precedes or coincides with morphologic changes in cervical cells signifying cervical cancer.<ref name="Ref13"/>
Results:
The result is expressed on percentage of analyzed ectocervical cells that overexpress oncoproteins E6 and E7. If this percentage is over 2% the HPV OncoTect result is positive, if it is lower it is a negative result.
*A negative result means there is no overexpression of high-risk HPV oncoproteins E6/E7. With a negative result the risk of have a cervical cancer in the future is almost null.
*A positive result means the viral DNA has been integrated into the cell genome which results in an overexpression of E6/E7 proteins. If the result of Pap smear is negative but HPV OncoTect result is positive the gynecologist should repeat both tests in 6-12 months. If both tests are positive it is needed a colposcopy or biopsy to confirm the diagnostic.
The sensitivity of HPV OncoTect is higher than a single Pap smear<ref name="Ref13"/> so this test in adjunct to the Pap smear would give a sensitivity of 100% as a primary screening tool. The specificity and positive predictive value are also higher than other HPV detection techniques. This might be very useful in screening young women, a cohort in which the prevalence of HPV DNA positivity may be as high as 20%.

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