Human Papilloma Virus (HPV) is among the most prevalent sexually transmitted diseases and it causes cervical cancer, the 4^th most prevalent type of cancer in women. The infection generally persists without any symptoms and if it is not eliminated by the body, it can insidiously lead to cervical cancer over the years. Studies show that approximately 80 percent of the population is at life-time risk of contracting HPV virus. There are vaccines that can provide almost one hundred percent protection against HPV Types 16 and 18, which are the cause of most cervical cancer cases. Assoc. Prof. Ömer Lütfi Tapısız, M.D., the Head of Gynecology and Obstetrics Department of Güven Hospital, informs about HPV infections and vaccines.

What is Human Papilloma Virus (HPV)?

It is a double-helix DNA virus, which causes infection in both men and women and usually involve the genital organs (Figure). The fact that HPV may lead to genital cancers was first stated by Harald zur Hausen in 1970’s and then, DNA sequences of HPV were shown in cells of cervical cancer. Out of over two hundred types, a small part of HPV viruses cause changes in cells. Generally, types of HPV that cause infection are divided into high- and low-risk HPVs, depending on their tendency to cause cancer.

• Low risk HPVs: The most prevalent low-risk types of HPV are; 6, 11, 40, 42, 43, 44, 54, 61, 70, 72 and 81.
• High-risk HPVs: The most prevalent high-risk types of HPV are: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68. Cervical cancer is most commonly caused by Type 16 and 18.

How is HPV transmitted?

The virus is transmitted sexually, but a proper sexual intercourse is not a necessity for the transmission. Skin or mucosal contact is sufficient for the contraction. In this context, the virus can spread when penis and scrotum of an infected person contacts the vagina or external female genital skin. Research shows that the virus is not transmitted through sharing towels, clothes and bed sheets or contact with inanimate objects such as toilet seat or door knobs. Also, there is lack of concrete evidence that the virus spreads through kissing. One should always remember that the virus will continue spreading from infected people even though they do not have any symptoms.

Does use of condoms during sexual intercourse prevent spread of HPV?

HPV virus is mainly transmitted during sexual intercourse. Therefore, using condoms lower the risk of transmission significantly. However, as stated above, contact of skin and/or mucosa is enough for transmitting the virus. In this context, although condoms prevent the contact between penis and vagina, it cannot prevent the contact with other genital organs and cannot entirely prevent the risk of transmission.

What are the symptoms of HPV infection?

HPV virus may not cause any symptoms. The most common symptom is the warts that appear 2 to 6 months after contracting the virus. Genital warts can be seen at vulva, vagina, cervix and/or anus in women and at penis, scrotum and/or anus in men; they are characterized with flat lesions, small stalked or cauliflower-like eruptions or swelling. Genital lesions are most commonly caused by low-risk types of HPV, namely HPV 6 and 11. High-risk HPVs can live in cells without causing any significant symptoms and they may lead to precancerous changes, translating into cancer in cervix, vagina, vulva, penis and oropharynx over many years. Here, it is important to know that HPV infections do not necessarily cause cancer and, even if it does, the process will take many years.

What are the causes that prevent spontaneous regression of HPV infection and make it spread?

The virus regresses on its own within 2 years in approximately 90 percent of people infected with HPV. The factors that lead to the spread by preventing the spontaneous regression may be listed as follows:

• Weak immune system
• Chemotherapy and radiotherapy
• Smoking
• Frequently recurring genital diseases other than HPV.
• Traumas
• Long term use of steroid agents, which may lead to weakened immune system
• Insomnia, tiredness
• Pregnancy
• Folic acid and/or beta carotene deficiency

How is HPV virus detected and diagnosed?

Diagnosis can be made by biopsying the warts in a pelvic exam or, if such a lesion does not exist, vaginal or cervical discharge can be smeared and DNA sequences of the HPV virus can be examined in those specimens. Thus, type of HPV virus is identified and a high-risk HPV can be detected. If a high-risk HPV is present, it is crucial to visit an experienced Gynecologist and Obstetrician for further examination and treatment. In addition, HPV infection can be detected by identifying the cellular changes that may be caused by HPV virus in a PAP test. Considering the fact that HPV infection may not cause any symptoms, one should be aware that regular HPV test and/or cervical PAP test are crucial for diagnosing the condition and taking necessary precautions before it transforms into a cervical cancer. According to the national cancer screening standards, every woman in the age range of 30 to 60 years is screened with Human Papilloma Virus (HPV) and Pap tests in our country.

How is HPV infection treated?

Today, a medication treatment that eradicates HPV is not present. It should be known that minimum 80 percent of healthy individuals with a well-functioning immune system will completely overcome the virus. Special treatments are planned for the lesions caused by the virus in management of HPV infection. If the virus has caused warts, called condyloma, the warts may be surgically excised, destroyed with electrocautery, frozen with cryotherapy or treated with medications or certain specialized chemical agents. If precancerous lesions have developed in the vulva, vagina or cervix, those lesions should be closely followed up and surgical treatment algorithm, if necessary, should be planned without wasting any time.

What are considerations for protection against HPV infection.

As HPV infection is mainly transmitted by sexual intercourse and contact, each sexually active person is at risk of HPV infection. Use of condom prevents penis from contacting the vagina and therefore, the risk of transmission reduces, but it does not, unfortunately, offer complete protection. Thus, the most appropriate protection approach is to avoid having sexual intercourse with those who carry the risk of sexually transmitted infection. Also, having sexual intercourse with only one partner will minimize the risk of transmission. Today, there are vaccines that offer almost a hundred percent protection against types of HPV, which cause genital warts and cervical/vulvar-vaginal cancers commonly.

Does HPV vaccine prevent HPV infection? Who should get HPV vaccine? / Is there any age limitation for HPV vaccine?/ How is HPV vaccine administered?

Today, there are three different types of HPV vaccine. Those are:

• Bivalent HPV vaccine: Vaccine for high-risk HPV Types 16 and 18 that account for 70% of cervical cancer cases.
• Quadrivalent HPV vaccine: Vaccine for low-risk HPV types 6 and 11 causing the genital warts (condyloma) and for HPV types 16 and 18.
• Nonavalent HPV vaccine: Vaccine for HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58

In our country, bivalent and quadrivalent vaccines are available; nonavalent vaccine has not been supplied yet. The recommended age for HPV immunization is 9-14 years of age, because adolescents are not sexually active and the best immune response to the vaccine is obtained in this age range. Considering current evidences, the most appropriate age for both girls and boys is 11-12 and it is recommended to administer catch-up vaccination until 26 years of age (15-26). Studies show that it is sufficient to administer the vaccine in two doses, as the immune response is more active in people younger than 15. HPV vaccines approved by the Food and Drug Administration (FDA) for use until 45 years of age for both men and women are recommended to be administered in 3 doses for individuals aged above 15.

It should be known that HPV vaccines administered at appropriate doses and age intervals before being sexually active will provide almost a hundred percent protection against the relevant HPV type and infection. However, considering that there are more than 200 types of HPV, one should always remember that current vaccines cannot provide protection against all HPV infections.

Indications and administration details regarding all three vaccines are specified in the table below.

Who should not be immunized for HPV?

Although the Food and Drug Administration (U.S. FDA) has classified HPV vaccine as pregnancy category “B”, today there is consensus on avoiding administration of HPV vaccines for pregnant women due to scarce human studies. If the vaccination protocol has already been started before pregnancy or the patient has became pregnant in the immunization interval, it is recommended to consult with an experienced Gynecologist and Obstetrician to modify the vaccination schedule. Those who suffer from severe disease are not suitable for HPV immunization. Vaccination schedule can be planned after the disease is cured and the immunization is approved by the primary doctor. If the person is prone to allergies, especially latex or yeast allergy, relevant doctor should be informed and the immunization should be planned under supervision of physician. If a life-threatening allergic reaction has developed during administration of the first dose, subsequent doses should be skipped. For breastfeeding mothers, vaccine can be administered upon the recommendation of a physician.

Is HPV vaccine beneficial for sexually active individuals?

It is a false belief that all sexually active individuals would contract HPV infection. In this sense, even if the patient is sexually active, the vaccine can offer protection against infections unless the patient has not been infected by any type of HPV covered by the vaccine. In conclusion, the vaccine will also be beneficial for sexually active individuals.

Is there any side effect of HPV vaccine?

Pain, swelling and redness at the administration site are the most significant adverse effects of the vaccine. Sometimes, dizziness and syncope may develop after the administration. Such side effects can be eliminated when the patient rests in sitting position for 15 minutes after the injection. Headache, nausea-vomiting, tiredness and fatigue may occur in some of the patients. Although the vaccine leads to almost no severe, life-threatening side effect, adverse effects of the vaccine have been still studied.

Is there risk of cervical cancer after HPV vaccine is administered? Is Pap test necessary after vaccination?

HPV vaccines provide protection against high-risk HPV types 16 and 18 causing 70% of cervical cancer cases. Since the vaccine does not offer protection against other high-risk HPV types included in etiology of cancer, it is necessary to remember that the vaccinated people are also at risk of cervical cancer. It is, therefore, important that those people have cervical cancer screenings, including Pap test, at regular intervals.