For the medical profession.

HPV and Oncogenesis

What is the difference between HPV infection and precancerosis?

An HPV infection is present if human Papilloma virus penetrate into the human squamous epithelium via microlesions that reach down to the basal layer. Having reached the basal cells, the virus introduces its DNA into the nucleus of the human host cell. The papilloma virus typically resides in the basal layer without interfering with the cell cycle of the infected cell.

One could call this stage a “peaceful co-existence”: the virus resides in the cells without causing any damage. During this stage, which is also described as a latent or subclinical infection, the virus uses the human cells to multiply. There are no clinically relevant symptoms or signs of the present HPV infection. An infection can remain in its latent state for up to several years and often clears itself.

When the virus starts to integrate its viral DNA into the human DNA, it actively affects the cell cycle. As a result, changes in cellular morphology can be observed. Pathologists call this malignant cell growth pre-cancerous lesions or pre-cancerosis.

What are the most common routes for HPV infection?Accordion Item

HPV16 is a ubiquitously present oncogenic virus. You can get into contact with the virus and get infected anywhere. Most infections are transient and clear themselves spontaneously, without the need for any intervention.

Sexual intercourse is considered to be the most frequent route of infection for HPV16. Transmissions to newborns when passing through the birth canal have been observed, but this is considered a less frequent route of infection.

Can the HPV virus be transmitted by kissing?

Kissing cannot be excluded as a path of transmission. However, the probability of a transmission via kissing is low. Only single cases of transmission probably by kissing have been described in the scientific literature.

Can HPV-induced tumors appear in the pharyngeal area as well?

Yes, they can. It is well established in the scientific literature that HPV-induced tumors appear in the rear part of the oral cavity and in the oropharyngeal area, as well as the anogenital area. Males develop HPV-induced tumors in the oropharyngeal region more frequently than females. Females, on the other hand, are more likely to develop HPV-induced tumors in the anogenital region.

Do Psoriasis patients have a higher risk of suffering from HPV induced tumors?

The scientific literature on this topic is sparse and does not allow any firm conclusions yet. Boffetta and colleagues (Cancer Risk in a Population-Based Cohort of Patients Hospitalized for Psoriasis in Sweden, J Invest Dermatol. 2001 Dec;117(6):1531-7) describe higher standardized incidence rates for oral and pharyngeal cancer, as well as vulvar and penile cancer for patients with Psoriasis. However, further data are needed to confirm this finding.

Is it recommended to use Prevo-Check® for patients with Condylomata acuminata?

Patients with Condylomata acuminata show a higher standardized incidence rate for HPV16 induced tumors. High risk papilloma virus has been identified in over a third of the genital warts of male patients and in over 50% of the genital warts of female patients. HPV16 has been isolated from genital warts of 20% of patients with Condylomata acuminata.

More information on the relevant literature references and on the risks associated with Condylomata acuminata can be found in our White paper series, part III.

How many patients are diagnosed with oropharyngeal cancer in Germany each year?

The incidence of oropharyngeal carcinoma in Germany was 15,000 in 2014 (Robert-Koch-Institute). According to the HPV center report, about 55% of these cases were caused by HPV.

Where in the oral cavity and pharynx are HPV-induced tumors most likely to be found?

HPV16-induced tumors are particularly prevalent in the rear part of the oral cavity and in the pharyngeal region. The majority of carcinoma found at the base of the tongue and in the oropharynx are caused by HPV.

Screening with Prevo-Check®

From what age do you recommend offering screening with Prevo-Check®?

Anyone at any age can develop HPV16-induced tumors. However, data by the Robert Koch-Institute show an increased rate of cancer of the oral cavity and pharynx for persons aged 40 or over. However, certain risk factors increase the probability of developing HPV16-induced tumors even at a younger age.

These factors include: immunodeficiencies, disorders of the immune system, Condylomata acuminata or HPV16-induced tumors in the history of patients or their partners.

We therefore recommend regular physical examination and screening with Prevo-Check® for patients who are 40 years or older, as well as patients at any age if they belong to one of the risk groups. Regular screening is also recommended for partners of high risk patients. Read more about risk groups here.

Do I still have to send samples to a lab for further clarification if I use Prevo-Check® in my practice?

Please do not change your current diagnostic procedures. If you find something suspicious during the examination of a patient, follow the usual pathway for diagnosis and referral.

Prevo-Check® complements your existing pathways by providing an opportunity to find HPV-induced malignancies in patients without any apparent symptoms. This means that you are more likely to detect tumors early that would otherwise go unnoticed for much longer.

Is Prevo-Check® a valid test?

Prevo-Check® is an officially approved and CE-marked IVD product for which clinical performance data have been established and validated. These data show a clinical sensitivity of up to 95%, and a clinical specificity of over 99%.

Which type of sample material can be used for Prevo-Check®?

To run Prevo-Check®, you only need one drop of capillary blood, either from the finger tip or ear lobe. Blood serum may also be used.

Which monovettes can be used for collecting venous blood?

You can use your standard monovette for the collection of serum samples from venous blood.

Sometimes the T-line is weak

The presence of a T-line always indicates a negative, i.e. normal, result, even if the band is very weak.

Why is Prevo-Check® sometimes showing a weak T-line and sometimes a stronger one?

There may be several reasons for the varying intensity of the T-line, not all of which relate to the physiological parameters that are being measured.

Physiological parameters affecting T-line intensity:

The amount of DRH1 antibodies present in the sample will affect the intensity of the T-line. Please note that even a weak T-line is to be considered a negative result which does not require any follow-up. Sometimes users feel unsure of how to interpret a weak T line. In these cases, please contact the Abviris team for further support.

Other factors affecting T-line intensity:

The membrane of the test cassette can sometimes be colored reddish if you use whole blood to perform Prevo-Check®. This reduces the contrast between the strip and the T-line, which makes the T-line appear faded. To minimize this effect, Prevo-Check has an inbuilt filter underneath the sample field which keeps the red blood cells away from the test membrane. However, in some cases erythrocytes may lyse, for example due to genetic conditions or the presence of drugs in the blood. As a result, haemoglobin is released and leaks through the filter, coloring the test strip red.

What would be the next steps if Prevo-Check® shows a positive result but visually I cannot see anything suspicious?

Prevo-Check® is a highly specific test, meaning that false positive results are rare. A positive result should therefore always be followed up.

Before you proceed, ask your patient once again if they are vaccinated against HPV. HPV vaccinations increase HPV16 L1-antibody levels in the blood and lead to positive Prevo-Check® test results.

A positive result in non-vaccinated patients should be followed up by a detailed visual examination of the areas that are at risk of HPV16-induced tumors, i.e. in the oropharynx and the anogenital region. Swabs should be taken from any region with suspected abnormalities.

If you cannot find any abnormalities despite a positive Prevo-Check® test result, it is advisable to have the mucosa re-examined by the appropriate specialists within one year.

Managing patients

When should a patient with Condylomata acuminata be invited for a follow up after tumor removal?

There are national and international guidelines defining the schedules for follow-up visits. We recommend following the schedule relevant to your country. For Germany, these guidelines are publicised by „Die Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V.