HPV is a virus with non-enveloped DNA consisting of 72 parts. Its DNA is double helix inside a 20-sided capsule. It is small in size (only 55 nanometers). It is heat resistant. There are nearly 200 types of HPV and 40 of them involve the genital area. Other types are associated with many diseases and tumors in the body. It is located in the epithelium of the vagina, vulva, anus, penis and perianal region. HPV has also been found in the upper respiratory tract epithelium, larynx, pharynx, and esophagus.
Information about HPV goes back to Roman times. The warriors who went to the east in this period came across warts when they returned. After herpes was blamed for cervical cancer until the mid-80s, it was understood that HPV was the cause of this cancer. 99% of patients with this type of cancer have HPV. 70% of them have type 16 and 18. Most sexually active men and women will get HPV. The prevalence of HPV in the community is much higher than is known. It appears more often in young people. The reason for this is that the epithelium is not fully formed in young people and the immune response is less. In the United States, 16% of the population is infected with HPV. The probability of having more than one type of HPV in the same person is 40%. In this case, an infection occurs that can turn into cancer more severely.
What are the risk factors associated with HPV?
Sexual activity:
Especially those who have sexual intercourse close to the first menstruation are at the highest risk of HPV infection. The reason for this is that the epithelium in the cervix is not fully developed at this age. The greater the number of partners, the greater the risk. This risk is reduced when condoms are used. Being polygamous or having a partner with cervical cancer increases the risk. When HPV is taken once, the excess number of partners in the course of cancer does not have a significant effect on cancer stages.
Birth control drugs:
Cervical cancer risk increases in women who use this drug for more than 5 years. They use condom less. Also, the structure of the cervix epithelium deteriorates in those who use these drugs. Folic acid decreases in the blood. This causes megaloblastic changes in the epithelium. 5 years of use increases the risk 5 times, 10 years of use increases the risk 10 times.
Cigarette:
Nicotine, phenols and hydrocarbons in cigarettes increase the risk. Smoking causes a 2-fold increase in risk. They cause DNA damage and delay the immune response. Adenocancers are not affected by smoking.
Number of Births:
The risk is much higher in women who have given birth 5 or more times (2.5 times). During pregnancy, folic acid decreases, cervical epithelium changes, and progesterone increases.
Diet:
The risk was reduced with vitamin C, vitamin A and vitamin E. Folic acid deficiency increases the development of CIN 4 times.
Immunosuppression:
HPV and CIN cases are 24 times more common in HIV-positive women. HPV and its associated cancers are 16 times more common in renal transplant patients. Therefore, it is seen how important the immune system is in HPV infection. In addition, low socioeconomic level also increases the risk.
The Relationship Between Cervical Cancer and HPV
Cervical cancer is an important women’s health problem, as it ranks second after breast cancer among women’s cancers worldwide. The World Health Organization (WHO) estimates that more than 2 million women worldwide have cervical cancer. 685 women die every day from cervical cancer, and about 250,000 women die every year. Every year, 80% of 500,000 new cases occur in developing countries.
According to the 2004 Health Statistics of the Ministry of Health, cervical cancer, which constitutes 3% of all cancers seen in women in Turkey, ranks second among gynecological cancers. According to the data of İzmir Cancer Monitoring and Control Center (KİDEM), the annual incidence rate of cervical cancers between 1996-2000 in İzmir is 5.5 per 100,000.
It is discussed whether the fact that cervical cancer is less common in our country compared to other cancers is a real situation or whether it is due to the inadequacy of the follow-up and notification system.
Cervical cancer is a preventable disease with a known causative agent. Today, HPV DNA has been detected in more than 99% of cervical cancer cases and more than 94% of cervical intraepithelial neoplasia (CIN) cases. Indirect risk factors for cervical cancer are; smoking, herpes simplex type-2, other sexually transmitted agents (including chlamydia), vitamin C, beta carotene, folate deficiency, oral contraceptives, socioeconomic insufficiency, black race, early age coitus, polygamy, women with multiple partners, poor Although the effects and mechanisms of indirect factors are not clear, they are thought to accelerate the carcinogenic process of HPV. It is stated that HPV plays a role in the etiology of 85% of anal cancers, 50% of vulva, vagina and penile cancers, and 20% of oropharyngeal cancers other than cervical cancer.
History of HPV
Genital warts (accuminate) have been known since ancient Greece and Rome, and the term “condyloma” describes the “fig-like” formation of genital warts. This term is also used today to describe both syphilis (condyloma lata) and HPV-related lesions.
At the beginning of the 20th century, Ciuffo demonstrated human-to-human transmission using a cell-free extract from wart tissue and talked about the viral etiology of human warts. In the late 1940s, prison volunteers were injected with genital wart extract, and wart formation was detected at the extragenital injection sites, proving contagious. Another event confirming the venereal nature of the viruses was the observation that penile warts developed in soldiers returning from the Korean War, and genital warts were observed in their spouses after a while. In the light of all these data, it was thought that genital warts could be caused by an infectious factor, and its infectivity from individual to individual was started to be investigated.
Classification of HPV
At the end of the 1960s, viral particles were detected in genital warts by electron microscopy and it was determined that these particles showed a great similarity to those of skin warts. Thus, it has been accepted that HPV is an infectious agent responsible for skin and genital warts. In 1976, Meisels first demonstrated a relationship between CIN and HPV. In the same year, Zur Hausen stated that HPV is a sexually transmitted carcinogen and since then it has been known that the female genital tract is associated with HPV with CIN, carcinoma in-situ (CIS) and invasive squamous cell carcinomas. Identification of these viruses and the detection of some types, especially those that play a role in the formation of benign, premalignant, malignant and malignant squamous lesions, has increased the interest in these viruses.
HPVs are generally examined in three groups.
I. Cutaneous Types:
HPVs that cause wart formation outside the anogenital region are in this group.
II. Epidermodysplasia Verruciformis (EV) types:
It progresses to squamous cancer of the skin.
III. Mucosal Types:
Of the 120 identified HPV types, 40 affect the genital/nongenital mucosa by infecting the genital area. This group of HPVs affects the anogenital system (vulva, vagina, cervix, anal canal and penis), respiratory and digestive tract, as well as the oral cavity. Genital mucosal types cause a wide range of clinical outcomes, from asymptomatic infections to genital warts to persistent infections causing malignancy. These results vary depending on the type of HPV. Mucosal HPV types are examined under three headings according to their risk of causing cervical cancer.
Classification of HPV Types According to Risk Categories:
- Low Risk Types 6,11,30,40,42,43,44,54,61,70,72,81
- Possible High-Risk Types 26,53,66,68,73,82
- High Risk Types 16,18,31,33,35,39,45,51,52,56,58,59
While HPV 16 was detected in approximately 50% of cervical cancers, HPV 18 was detected in 15%; HPV 31 and 45 detected in 10-15% HPV Types 16 and 18 are responsible for approximately 70% of cervical cancer and cervical intraepithelial neoplasia (CIN) cases.
The Course of HPV Infection
Three possible outcomes may develop after contact with HPV:
- I. Infection does not develop.
- II. Latent/inactive infection develops.
There is no visible lesion with the eye or microscope. Most HPV infections are transient and asymptomatic. However, in ~10% women, the presence of HPV can be demonstrated in cytologically normal cervical epithelium by techniques such as PCR (Polymerase chain reaction test) and Hybrid Capture. About 70% of HPV DNA positive women become negative within one year and 91% within two years. Persistent (recurrent) HPV infection develops in 10% of HPV positive women. - III. There is a clinically visible lesion.
It includes visible genital warts and pathological abnormalities detected by microscope.
HPV Scans
Pap smear test is used as the classical screening method. This test is valuable in detecting dysplasia. The sensitivity rate for the test is stated as 57%. The main risk factor for cervical abnormalities is HPV, and it is stated that viral DNA can be detected by PCR method. With this method, 13 high-risk HPV types can be detected. Due to the low sensitivity of the Pap smear test and showing only cervical dysplasia, not the HPV virus, it is generally accepted that the use of HPV tests and cervical smear combined with it increases the possibility of early diagnosis.
HPV tests can also be useful when cervical smear results are not directive. In general, it is recommended to look for viral DNA in people with LSIL in pap smear screening. It is stated that screening can be started with pap smear test with the beginning of sexual intercourse, if the age of first sexual intercourse is under 18 years old, screening can be started after three years, and the frequency can be continued once a year. It is emphasized that pap smear test should be continued in vaccinated people. It will be seen how practices will change in pap smear follow-up after long-term study results are obtained.
HPV Diagnosis
The probable diagnosis of HPV infection can be made by demonstrating koilocytosis in histological examination microscopically. Detection of cytological changes indicating the presence of viral infection with Papanicolau stain is used today for screening in cervicovaginal cells. Dr. This method, introduced by Papanicolau, is known as Pap smear for short. However, since its sensitivity is low, immunological or nucleic acid diagnostic methods are used for definitive diagnosis.