Frequently asked questions

Which tools and equipment do I need for performing GynTect<sup>®</sup>?

GynTect® is a PCR-based test, during which the methylation of certain DNA regions is detected. Prior to the performance of the PCR test the patient sample is treated chemically. You receive the Bisulfite conversion kit required for this chemical treatment from the GynTect® distributor. For the performance of the bisulfite treatment you need a heating block with cooling option, e.g. a simple thermocycler with a block for 0.5 ml reaction tubes. The GynTect® assay currently is established on the realtime-PCR platforms Abi7300 and Abi7500 (Life Technologies).

When should I start attending cervical cancer screening?

The guidelines differ between the European countries. Germany and Austria offer regular annual screening with the Pap test from the age of 20 and 18, respectively. In other countries women without cytology findings are rescreened only every three to five years.

What is a Pap test?

Nowadays the most frequently used method in cervical cancer screening is a microscopic inspection of a smear from the cervix of the patient, the so-called Pap test. This Pap test may, through appearance of untypical cells, indicate the presence of a disease at the cervix. But only few of these abnormal findings in the test indicate the formation or even presence of cancer. Many studies have demonstrated that many of the surgeries performed after an abnormal Pap test, so-called conizations, could be avoided. These surgeries can have adverse effects for women in their reproductive phase, such as higher risk of perinatal loss or preterm birth.

What happens if cellular changes are observed?

Weak cellular changes, so-called mild dysplasias, most frequently heal spontaneously. Therefore they are checked regularly. HPV testing may contribute to the clarification of the question if a dysplasia has the potential to develop into a carcinoma. In case of a negative HPV test result the probability for progression to cancer is very low.

In the case of more severe cellular changes, together with an incident HPV infection, a specific examination, a so-called colposcopy may be performed. During this examination a biopsy may be taken for further diagnoses. These diagnoses may allow to determine the degree of the dysplasia.

In patients with good general health who have a good condition, smaller high-grade dysplasias may be removed surgically by laser vaporization or diathermy. In case of tumors, a connotation is performed. Patients with poor general health and/or with later stage carcinomas may initially get radiation therapy; a combination with chemotherapy is also frequently used in such cases.

Which other diagnostic measures besides the Pap test can be performed?

In most European countries, testing for HPV is currently not performed directly as a screening method. Instead it is frequently used as a triage of women, who already were diagnosed with abnormalities in the Pap test. Then it is also paid by health insurances.

What are human papillomaviruses (HPV)?

Human papillomaviruses are a group of viruses that may evoke warts. All these HPV types differ genetically, and they can infect the skin or mucosal tissue, not only but preferentially in the anogenital region. HPV infections are always locally restricted and do not spread to more distant parts/organs of the body.

Of the more than 150 types of HPV, a small group, the so-called high-risk human papillomaviruses (hr-HPV), may cause precancerous lesions and, if not diagnosed and treated early, cancer (e. g. cervical cancer, tonsillar cancer).

What are low- and high-risk HPV types?

The genital HPV types are classified into two groups: low and high risk HPV. Low-risk HPV (e.g. 6, 11, 42, 43, 44) are almost never detected in case of a cervical cancer. High-risk HPV types (e.g. 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58) are detected in 99.7% of all cervical cancer cases. In 70% of the cases, HPV16 and HPV18 are detected. Only women with long-term infection with high-risk HPV and subsequent cervical lesions have a risk of developing precancerous lesions and cancer. It is well-established nowadays that HPV infection ist he main risk factor for the development of cervical cancer.

How can I get to know if I am infected with HPV?

HPV tests are used in order to detect an infection. If the HPV test yields a negative result, a precancerous lesion or even cancer can be excluded with 99% probability. Only such a negative result is of high value for the patient. Only a small part of the women infected with HPV will develop a cervical disease. That’s why we have developed GynTect®, which detects markers specifically occurring in precancerous and cancer cells.

How can I minimize the risk of getting infected with HPV?

The only way to minimize the risk of getting infected by HPV is sexual abstinence. Condoms offer rather good protection, since HPV, like other sexually transmitted diseases are transferred through exchange of body fluids. It is recommended to get immunized against the two most important cancer-causing strains HPV16 and HPV18 as early as possible (the German STIKO now recommends immunization from the age of 9 – 13). But even if immunized, you should continue participating in screening programs.

How high is the probability to get infected with HPV?

Genital HPV infections occur very frequently. In fact, human papillomaviruses are the most frequently sexually transmitted infectous agents. HPV are mainly, but not exclusively transmitted sexually. It is estimated that the probability to get infected with HPV ranges between 75 and 90%, for both, men and women.

For whom have we developed GynTect<sup>®</sup>?

According to the already performed trials, GynTect® is suitable for all women who want to get further clarification after an abnormal Pap smear and/or a positive HPV test, if surgery is already required or if a watchful waiting strategy could demonstrate if an HPV infection and a tissue abnormality may heal without treatment.

What does a positive GynTect® result mean?

Results obtained during clinical trials indicate that upon a positive GynTect® test result a severe cervical lesion, a so-called CIN3, or even a cervical carcinoma (from a low-grade CIN1 or CIN2) may develop or already be present. Invasive diagnostics (colposcopy and, if required, biopsy, both in a specialized colposcopy clinic) should be performed after a positive GynTect® test result. During this examination conspicuous surface of the cervix should be examined very thoroughly, and biopsies taken during this examination should be diagnosed by histopathology.

In case of a negative test result a precancerous leson or cancer can almost be excluded. We recommend a re-examination after 6 months, with HPV testing performed first.

How can GynTect<sup>®</sup> improve cervical cancer screening?

GynTect® is a reliable molecular test that may clarify if a patient with unclear Pap test results (Pap III, PAP IIID, evtl. Pap IVa) and/or an HPV infection already has a precancerous lesion of carcinoma that requires treatment.

GynTect® aims at the detection of specific epigenetic changes that may occur early in cervical carcinogenesis. If these changes are not detectable, watchful waiting may help avoiding unnecessary surgery.

What are the advantages of GynTect<sup>®</sup> compared to a normal cervical examination?

Additional tests are required in order to clarify if a precancerous lesion or cancer is the reason for an abnormal Pap smear result. GynTect® is an easy to perform and reliable test which detects epigenetic changes specifically occuring in cancer tissue. The same cervical smear material that is currently used for Pap testing is used for GynTect®.

What are epigenetic markers?

If a normal cell develops into a tumor cell, this leaves traces in the genetic material, the DNA, of the tumor cells. Such epigenetic traces, a specific methylation of certain DNA regions, are detected with tests developed by oncgnostics. Our studies demonstrate that the markers validated for GynTect®, can easily be detected in smear material from the cervix of women with disease.

How can I get a GynTect<sup>®</sup> test done?

If you are interested in GynTect®, please contact your gynaecologist. He may then contact oncgnostics and get all the information and materials required for getting the test performed.

What are the advantages of GynTect<sup>®</sup> compared to a normal cervical examination?

In oder to determine whether an abnormal Pap smear result originates from a cervical disease requiring treatment, additional tests and examinations are required. With our GynTect® procedure we reliably identify epigenetic changes which occur specifically in cancer tissue. For this test we use the same material that is currently used for the Pap test.

How long does it take to get a GynTect<sup>®</sup> test result?


GynTect® can be performed within one lab working day, independent of the number of tests performed in parallel. The hands-on time, which includes sample preparation (10 min) prior to the bisulfite treatment and a purification (30 min) after this chemical treatment, as well as the set-up of the PCR reaction (10 – 30 min depending upon the number of samples), is readily comprehensible. At the end of the PCR run max. 30 min are required for the evaluation of the results.

Which controls are included in a GynTect<sup>®</sup> run?

A GynTect® assay for a patient sample includes two internal controls: (1) the detection of a DNA fragment which only functions if the sample material after bisulfite treatment is of sufficient quality and quantity; this fragment does not contain methylated bases; (2) the detection of a methylated DNA fragment which indicates that the methylation of the DNA has remained stable during sample transport and preparation.