What is HPV?

The abbreviation HPV stands for “Human Papillomavirus”.

There are over 100 different types of HPV. HPV has been around for thousands of years, as studies on mummies have shown. HPV can also be found in a wide variety of body regions such as fingernails. For reasons that have not yet been clarified, an HPV infection only leads to problems in certain parts of the body. These include the genital tract, the area of the anus and the pharynx. Transmission in these body regions takes place through skin contact and the majority of the time during sexual intercourse, anal and oral sex.

The infection can lead to the growth of mostly small tumor-like nodules. The majority of these are benign, are called genital warts and in most cases they go away on their own. These changes are caused by the group of so-called “low-risk” viruses.

In contrast, viruses from the group of “high-risk” viruses can cause precancerous changes (dysplasia) and ultimately cancer, i.e. malignant tumors. This is primarily cervical cancer. Furthermore, rare to extremely rare carcinomas, for example in the area of the vagina (vaginal carcinoma), the vaginal entrance (vulva carcinoma), the anus (anal carcinoma), the nasopharynx (larynx and pharynx cancer) and the penis (penile carcinoma) can be caused by HPV.

The spread of HPV

HPV infection is a very common infection. According to large epidemiological studies, three out of four sexually active people will get HPV infection at some point.

In most cases, HPV infection causes no symptoms and goes away unnoticed. More detailed studies of HPV infection are only available for women. Young women are particularly affected. It was shown that the infection rate for women younger than 30 years is around 25% and for women older than 30 years it is only 8%.

The immune system is able to successfully fight and eliminate the infection with viruses from the “low-risk” group in an average of five months and with viruses in the “high-risk” group in eight months. In a two-year period, 90% of all women have overcome the infection. However, this “virus cleansing” can also fail to materialize and the virus infection can remain inactive, in individual cases even for many years. At different intervals, the infection can eventually cause pathological changes such as genital warts.

Due to this sometimes very long so-called “latency period” between infection and the development of changes, it is often very difficult in individual cases to identify the sexual partner who actually transmitted the infection and is also not important from a medical point of view. If a woman has a positive HPV test result, 70% of her male sexual partners are also infected with HPV.

Consequences of HPV infection

The HPV virus can penetrate through small injuries in the skin or mucous membrane and infect the so-called “basal cell layer”. By dividing, cells in this deep-lying layer produce those cells that slowly move towards the skin’s surface and are finally shed on the skin’s surface. There are neither blood nor lymphatic vessels in this most superficial layer of the skin and mucous membrane. Here it is much more difficult for the human immune system to produce an immune response against a pathogen than against pathogens inside the body.

Most will heal on their own

About 30 to 40 types of HPV colonize the genital tract. It cannot be stressed enough that the majority of all HPV infections clear up on their own and do not cause any symptoms. The most common HPV-induced changes are the so-called genital warts, or “condylomata acuminata” in Latin. These are almost exclusively caused by HPV types 6 and 11. The extent of the infestation is usually not very pronounced. Sometimes there are only a few, microscopic warts, which are only discovered by chance during a gynecological examination.

Sometimes, however, there is also a very intensive infestation of warts, which can be a few centimeters in diameter and, in extreme cases, can form entire wart lawns, which can affect not only the genital tract but also the rectal area.

CIN, VIN & AIN

The group of “high risk” viruses and here especially the types 16, 18, 45, 31 can cause precancerous changes, so-called dysplasia. The cervix is by far the most commonly affected part of the genital tract.

Pre-cancerous changes, i.e. dysplasia of the cervix, are referred to as “cervical intraepithelial neoplasia” (CIN). By analogy, dysplasia of the vagina is called “vaginal intraepithelial neoplasia” (VAIN), dysplasia of the vaginal entrance “vulvar intraepithelial neoplasia” (VIN), dysplasia of the intestinal outlet “anal intraepithelial neoplasia” (AIN). According to the severity of the dysplasia, these are classified as mild, moderate, or severe, depending on how much of the thickness of the skin layer above the basal cell layer is covered by HPV-altered cells. Taking the cervix as an example, these dysplasias (precancerous changes) are called CIN I in the case of mild dysplasia, CIN II dysplasia of moderate grade, or CIN III severe dysplasia. Only when all layers have been covered do these cells break through the basal cell layer and thus gain access to blood and lymphatic vessels. When the cells of the severe dysplasia have broken through the basal cell layer, the dysplasia has become an early carcinoma.

Diagnosis of HPV infection

HPV infection does not initially cause any symptoms, and most people are able to use their own immune systems to successfully fight the infection without realizing it. For this reason, it is also not necessary to search for HPV infection, especially since the knowledge that HPV infection is present can trigger feelings of insecurity, fear, anger and shame in many women. This circumstance then often impairs sexual behavior and impairs the pleasurable and fulfilling approach to sexuality. According to the latest guidelines, it is recommended that only women over the age of 30 should have an HPV test every 3 years. This is to avoid excessive controls.

It is therefore particularly important to convey that HPV infections are almost as common as infections with the common cold virus and that in the vast majority of cases this infection goes away on its own. For this reason, there is no need to be afraid of transmission, since almost everyone who is sexually active will get an HPV infection at some point. In addition, there is no treatment that has been proven to be effective against asymptomatic HPV infection.

The situation is different with the diagnosis of pathological changes that can be caused by an HPV infection. The first thing to mention here is the regular cancer smear (Pap smear) as part of the gynecological check-up at the gynecologist. A brush is used to stroke the surface of the cervix and the cells that get caught in the brush are smeared onto a slide and examined under a microscope. If an HPV infection has led to a precancerous change, there is a high probability that abnormal cells will be found in the smear. Depending on the degree of severity, the designation Pap IIID or Pap IV is chosen.
If such a result is now available, then the next step is to perform a colposcopy. The cervix is stained with an aqueous vinegar solution and viewed under a magnifying glass and, if necessary, a small tissue sample is obtained. This is then examined again under the microscope and a diagnosis such as CIN I to III (see above) is made. Colposcopy and biopsy is also the method of choice for diagnosing precancerous changes in the vagina (VAIN), the vaginal introitus (VIN) and the anal canal (AIN).

It is also possible to detect the virus. As with a smear test, a small brush is used to stroke the cervix and the brush is then placed in a tube. As part of a special laboratory test, the virus is then multiplied in the test tube using polymerase chain reaction (PCR) to such an extent that it can finally be detected. Two test methods are currently in common use. For example, with the cobas® test from Roche, only the virus types HPV 16 and 18 are determined from the group of “high-risk” types, all others are combined in a group, the so-called “pool”. With the PapilloCheck® test from Greiner, on the other hand, it can be determined which virus type is involved.

The different types of HPV therapy

The same applies to genital warts as to HPV infection: the majority of them regress by themselves with the help of the immune system.
Two forms of therapy are available for treatment: local therapy (creams, ointments and tinctures) to be carried out by the patient herself or local destruction by the doctor using cold, heat or laser therapy. However, the patient can only carry out local therapies if the warts are external, i.e. warts that the patient sees herself. Warts that affect the vagina or cervix are not suitable for such therapies.
Like genital warts, cervical dysplasia often resolves on its own and therefore does not always require treatment. For example, low-grade dysplasia (CIN I) regresses in over 80% of cases if left untreated. The likelihood of dysplasia resolving on its own decreases with increasing severity. CIN III changes only regress without treatment in about 10% of cases, but the percentage is much higher in women under the age of 25.

Conization

The surgical treatment of cervical dysplasia most frequently used in Austria is conization, which can be carried out using an outdated method with a knife or with the more gentle modern method using an electric loop (LLETZ method). The same applies to the dysplasias of the other localizations (VAIN, VIN, AIN). Low-grade dysplasia can be observed and higher grade dysplasia should either be surgically removed or locally destroyed, with laser therapy being the preferred method of destroying the changes.

A targeted drug treatment of HPV infections themselves or their sequelae, dysplasia, was not considered possible until recently.

Trichloroacetic acid in cervical dysplasia

It is important to us to spare women an operation as often as possible.

The current standard method for high-grade dysplasia is conization. The efficiency of this operation is high and the risk is manageable. Nevertheless, part of the cervix is removed and depending on the extent of the removal, the risk of preterm birth increases in women of childbearing age. On the other hand, it is a small surgical procedure that is usually performed under general anesthesia and many women would like to avoid it.

Under certain conditions, the treatment of cervical intraepithelial dysplasia (CIN) with trichloroacetic acid is possible and healing rates of 82% can be achieved after a single application. With a second treatment, the rate reaches over 90%.
The treatment takes place under local anesthesia in the surgery. You will suffer from increased discharge in the next 2-3 weeks, sick leave is not necessary.
Whether this application is suitable for you can only be decided after a summary of all findings and after a colposcopy carried out by us. We advise you comprehensively and decide together with you according to current medical standards which variant is most suitable for you.

Newspaper report: https://www.derstandard.at/story/2000033872030/auf-gebaermutterhalstrichloressigsaeure-als-therapie-fuer-krebsvorstufe

Study: https://journals.lww.com/greenjournal/Fulltext/2016/02000/Short_Term_Efficacy_of_Trichloroacetic_Acid_in_the.25.aspx

Trichloroacetic acid for condyloma treatment in pregnancy

Condylomas are common during pregnancy, but they do not automatically represent an obstacle to birth. A planned caesarean section is therefore only necessary in exceptional cases. Although condylomas can be cosmetically disturbing, they do not represent an increased risk of cancer. Standard drugs are not possible as therapy during pregnancy, as they could have an embryotoxic effect. In special cases, we carry out treatment with trichloroacetic acid in the surgery. This treatment has no effect on the unborn child.

HPV vaccination/ Gardasil9

The Gardasil 9 vaccine, which has been available since 2016, protects against HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58.

The vaccination is currently approved for girls and boys from the age of 9 and is paid for by statutory health insurance up to the age of 12. Contrary to popular belief, vaccination also makes sense in the case of an existing HPV infection or pre-cancerous stage that has gone through, since the natural infection with HP viruses does not produce any lasting immunity. The current recommendation is therefore to vaccinate between the ages of 9 and 45. Vaccination provides lifelong protection against the nine most common virus types and reduces the risk of CIN 2 and CIN 3 and genital warts by over 90%

Vaccination is not a substitute for routine screening for cervical cancer screening. Since no vaccine is 100% effective and GARDASIL 9 does not protect against every HPV type or against HPV infections that already exist at the time of vaccination, routine examinations (PAP tests) for the early detection of cervical cancer remain of crucial importance and should be carried out unchanged.

You are welcome to have vaccinations carried out in our surgery. Costs per vaccination are 200 euros.

Gardasil 9 efficacy study: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31821-4/fulltext

HPV Screening

As part of the current non-organized cervical cancer screening program, it is recommended that women over the age of 30 should have a validated HPV test at least every 3 years. This applies to HPV vaccinated and non-HPV vaccinated women. A routine co-testing, i.e. a simultaneous Pap smear, should be avoided; both methods can be used alternately.

HPV test for diagnosis

An HPV test can be used to determine whether you are infected with a high-risk or low-risk strain of HPV, but it can also determine what type of virus you have. With HPV 16, the chance of self-healing of a precancerous stage – dysplasia – is lower than with another HP virus strain. In the case of an unclear PAP smear – PAP III – the HPV detection is used to distinguish between a simple vaginal infection and a precancerous stage caused by HPV viruses.

HPV test for follow-up, operation/treatment follow-up

After a conization, an HPV test can be used to determine whether the HPV virus infection is still present. Even if the precancerous lesions have been removed in a healthy part during conization, the HPV virus infection can remain, which increases the risk of precancerous lesions recurring.

Immune modulation

The immunomodulator with the molecular formula C14H16N4 is a drug approved for the treatment of small, superficial basal cell skin cancers (basalioma), precancerous lesions of the skin on the face, back of the hands, forehead, bald head, nose and ears (actinic keratosis) and genital warts caused by chronic photodamage ( acuminate condylomata).

The immune modulator is not aimed directly at viruses and cancer cells, but intervenes in the immune system and helps the body to fight these changes itself. As an immunomodulator, it activates the skin’s immune system.

The immunomodulator causes a mild inflammatory response and binds to the toll-like receptor (TLR). The TRL is a surface molecule of immune cells, especially macrophages. If pathological substances (viruses and cancer cells) accumulate on it, the TLR transmits the signal “foreign” (“not belonging to the body”) to the immune system, and the immune system destroys these structures. Due to the mode of action of the immune modulator, there is often a short-term increase in body temperature and skin irritation and should not be used during pregnancy or breastfeeding.

In addition to the indications for which the immunomodulator is approved, there are other diseases in which this drug has proven to be very effective. This includes the treatment of pre-cancer diseases of the anal canal (AIN) and the vaginal entrance (VIN). Regarding new therapy concepts for the treatment of dysplasia of the cervix see treatment approach.