The number of people infected with human papillomavirus has significantly increased in the last 30 years and today HPV is considered to be the most common viral sexually transmitted disease. Most often it affects young sexually active women and men up to the age of 25, and is therefore a significant public health problem, which, if left treated, can lead to genital warts, cervical cancer, vaginal cancer and cancer of the male genital tract.
The cause of the infection is the human papillomavirus, a DNA virus from the Papillomaviridae family, the genus Papillomavirus. There are over 200 genotypes of HPV that can be divided into those that affect the skin and those that affect mucous membranes.
“Skin genotypes” usually infect the orbital epithelium of the skin, while their mucous counterparts infect the mucous membrane of the genital, respiratory and digestive tracts. According to their malignant potential, which is fully reached in cervical cancer, we divide the genotypes into two groups: low-risk and high-risk.
The most important low-risk genotypes are 6 and 11, which are responsible for the emergence of benign changes such as genital warts (condylomas). When it comes to high-risk genotypes, we must mention five genotypes that are responsible for 90% of HPV-induced cases of cervical cancer, these being 16, 18, 31, 33 and 45.
How Is HPV Transmitted and What Are the Risk Groups?
HPV is transmitted sexually, not only through penetration, but also by “skin on skin” contact in the genital area. Every sexually active person is in risk of getting an HPV infection, and most often it occurs in people younger than 25. People who become sexually active early on in their lives, those who often change partners, or have sex with a risky partner without a condom, and people with low socioeconomic status are at increased risk. Although this infection is usually transmitted sexually, sometimes it occurs in infants, children and virgins, so today it is believed that it can be transmitted in other ways.
Clinical Picture of HPV
Depending on the genotype of the virus that affects a person, we differentiate between benign and malignant forms of the disease. It is assumed that 50-80% of women get infected with HPV in their lifetime, with more than 50% of them being infected with high-risk HPV.
The infection may be:
- clinical (there is visible lesion)
- subclinical (tested with 3-5% acetic acid coating and colposcopy)
- latent (asymptomatic, tested by HPV typing)
The most common signs of infection are genital warts or condylomas – skin or mucous membranes, which may be spindle (condyloma acuminatum), flat (condyloma planum), papular (condyloma papulosa) and keratocytic. Extremely large condylomas are called gigantic condylomas. However, these changes are benign.
Some of the malignant forms of the diseases that are the result of infection with high-risk genotypes are:
- CIN (cervical intraepithelial neoplasia)
- VAIN (vaginal intraepithelial neoplasia)
- VIN (vulvar intraepithelial neoplasia)
- cervical cancer
Cervical Intraepithelial Neoplasia (CIN)
CIN represents premalignant intraepithelial changes in the cervix. It is directly linked to the HPV infection. According to Richart, there are three stages of CIN (depending on epithelial involvement):
- CIN I: mild dysplasia; only the lower third of the epithelium is affected
- CIN II: moderate to severe dysplasia; the lower and middle third of the epithelium are affected
- CIN III: severe dysplasia/carcinoma in situ; the complete epithelium over the basal membrane is affected
The aforementioned changes are most often asymptomatic; in rare cases can lesions be manifested by contact bleeding. They are diagnosed with the Pap test, which is the main method of screening for cervical cancer.
Vaginal Intraepithelial Neoplasia (VAIN)
Vaginal intraepithelial neoplasia (VAIN) is analogous to CIN and affects the platelet epithelium of the vagina. It is a subtle form of vaginal carcinoma.
There are three stages of VAIN:
- VAIN I (mild dysplasia)
- VAIN II (moderate dysplasia)
- VAIN III (severe dysplasia)
Usually there are no symptoms, notwithstanding the occasional bleeding discharge, which may or may not be accompanied by an unpleasant odor.
Vulvar Intraepithelial Neoplasia (VIN)
VIN stands for precancerous changes of the squamous epithelium of the vulva. Its frequency is on the rise, especially in younger women. As CIN and VAIN, it too has three stages and is also associated with the HPV infection. It is most commonly manifested by itching, peeling, unpleasant odor, long lasting discomfort in the area of the vulva, which affects sexual function and quality of life.
Cervical cancer takes second place when it comes to frequency of malignant cancers in women all around the world, and it continues to be the leading cause of mortality in third world countries. The human papillomavirus (HPV) is the major etiopathogenic culprit in cancer development.
Apart from HPV infections, smoking, alcohol, nutrition and oral contraceptives, vitamin deficiencies and immunosuppression also play a role. The screening method is the PAPA test, which detects premalignant lesions to prevent the infection’s late stage – cervical cancer.
It affects women of middle age or older women, but it can occur at any age, especially during fertile years. The main treatment method in the early stage is surgical procedure, while radiation and chemotherapy are used in the late stage.
Less frequent changes are:
- epidermodysplasia verruciformis – a rare autosomal recessive hereditary disease that carries a high risk of skin cancer. It is associated with HPV infection, including genotypes 5 and 8. As a result of HPV infection, there are numerous maculas and papules on the palms and feet
- bovenoid papulosis – a compound of a number of nodes most commonly located on the external genitalia; signs of cellular abnormalities similar to changes in Bowen’s disease or invasive spinocellular carcinoma are searched for histologically – HPV 16 is most commonly isolated
- erythroplasia Queyrat (Bowen’s glans penis disease) – it occurs almost exclusively in uncircumcised men and can evovlve into an invasive cancer in about 10-33% of cases. Patients typically address the physician when they notice solitary or multiple erythematosus plaques on the glans penis and mucosal epithelium, which do not heal. Symptoms include redness, ulceration, bleeding, pain, itching, disorientation, penile discharge, and inability to retract the foreskin. The causes of the disease are not fully known, but the supposed etiology involves chronic irritation, inflammation and chronic infections (human papillomavirus, HPV).
- PAIN (perineal intraepithelial neoplasia) – premalignant intraepithelial lesions affecting the perineum
- AIN (anal intraepithelial neoplasia) – premalignant intraepithelial lesions affecting the area of the anus
- PIN (penile intraepithelial neoplasia) – premalignant intraepithelial lesions affecting the area of the penis
- penile cancer – occurs in about 1% malignant tumors in men and 2 to 5% urogenital tumors. In some populations, it occurs more commonly, for example in Africans and Indians, where it accounts for 10 to 12% malignant tumors in men. It is etiologically linked with lack of hygiene, phimosis and retention of smegma under the foreskin, as well as the presence of Human papillomavirus. Circumcision is an almost foolproof protection against this disease. The most common histological form of penile cancer is planocellular carcinoma.
It should be noted that what we deal with is in most cases just an asymptomatic infection, which the immune system, the natural defense mechanism of the body “purifies” without further risk of progression to malignant forms. However, some people – mostly women – develop long-lasting infections of high-risk types, which is manifested by the CIN lesions that can progress to cervical cancer.