There is no doubt about the link between cervical cancer and human papillomavirus (HPV) infection. However, in most cases, the time between infection with a carcinogenic HPV strain and cervical cancer is 25 to 30 years or more and depends on the characteristics of the virus, the macro-organism and environmental conditions. With the advent of the HPV vaccine, the distinction between "fresh" and persistent infections, the assessment of the risk of persistence of HPV infection and its progression with the development of cervical cancer, and determining this risk in women of different age groups becomes fundamentally important.

A team of researchers from Costa Rica has conducted the largest observational study to study the natural process of HPV infection, the course of HPV infection and the development of cervical cancer in women. This study included more than 9,000 women aged 18 to 97 living in the Republic of Costa Rica. At the time of inclusion in the study, all women were examined using cervicography, a cytological examination of a cervical smear, an examination of the cervix and d '' an HPV presence test. The identification of cervical intraepithelial neoplasia (CIN) of more than stage 2 served as the basis for the withdrawal of the women from an observational study and for the necessary treatment.

A total of 9,175 women were included in the observational part of the study, of which 6,029 were assigned to the low-risk group with reconsideration after 5-7 years (the group called "passive observation"), and 2,115 to the group. high risk with control exams every 6-12 months for 7 years ("active observation" group). In addition, the active observation group also included separate subgroups of women at low risk of HPV infection (n = 540), as well as women who had not had sexual intercourse initially and who were became sexually active during the study (n = 410).

Of all the women included, 11.2% did not attend the follow-up visit and 5.5% dropped out of the study after 1-2 follow-up visits. The average follow-up period in this study was 6 to 7 years. The analysis of the results was carried out in 4 age groups: 18-25 years old, 26-33, 34-41; 42 and over. During the follow-up examinations, a cytological examination of the cervical smear and a test for the presence of HPV by PCR were carried out. If a CIN of more than 2 stages was detected, a colposcopy was performed and treatment was carried out.

The initial prevalence of HPV infection was 28.1% and 27.8% in the passive and active observation groups, respectively. The researchers found that women in the older age groups exhibited significantly more frequent persistence of HPV infection detected at the initial visit, compared to younger women (p less than 0.01). In addition, the vast majority of cases of CIN above 2 stages detected during follow-up (66 cases out of 85) were observed in women infected with the carcinogenic type of HPV during the initial visit.

Regardless of the age of the women, most of the newly diagnosed HPV infections resulted in spontaneous healing and did not lead to higher CIN development in stage 2 during the study. The total cumulative incidence of higher stage 2 CIN in the first HPV infections detected ranged from 2.1% to 6.2% in the first 3 years of observation.

It has been found that a possible decrease in age-related immunity does not increase the risk of progression of the first HPV infection detected with the development of a higher CIN at stage 3 for 3 years of observation. Thus, in women over 34 years of age, there has not been a single case of progression of cervical lesions to a CIN of more than 3 stages following a newly diagnosed HPV infection (17 cases), whereas in a group of women under 34, the development of CIN is greater than 3 stages was noted in 12.2% of cases (5 out of 41).

In addition, it has been found that the frequency of newly diagnosed HPV infections decreases significantly with age: from 35.9% in women aged 18 to 25 to 13.5% in women of 42 and over in the active observation group. The highest frequency of HPV infection newly diagnosed during the study (35.2%) was also observed in the group of women who did not have intercourse at the start and who became sexually active during the study.

The researchers concluded that the risk of developing cervical cancer is determined by the duration of the carcinogenic type of HPV infection, but does not depend on the presence of genital warts caused by HPV 6 or HPV 11, as well as the age of the woman. For the first time, HPV infections that can be prevented by vaccination with existing HPV vaccines do not pose a serious risk of developing cervical cancer in the near future for women of all ages, and most of these infections end for the first time in 2-3 years with spontaneous healing.

The HPV vaccines available today are preventive, that is, they prevent HPV infection and do not affect the course and prognosis of infection in previously infected women. Vaccinating girls before sexual activity reduces the likelihood of persistent infection with the carcinogenic type of HPV during the 25 to 30 years of life necessary for the development of cervical cancer, and vaccination of women over 30 is not economically feasible. By the age of 30, most women have already been infected with the types of HPV included in the vaccine; in older women, the frequency of first cases of HPV infection is significantly reduced, and HPV infections that occur in women in an older age group (over 42 years) do not generally progress not in stage 2-3 of the CIN. All this makes vaccination against HPV in women aged 30 to 40 years unjustified.

In addition, the results of an observational study change our understanding of the proper organization of screening programs for the presence of HPV infection. In particular, a single detection of HPV by PCR in women of all ages should not be a source of serious concern. The authors suggest a review after 12 months to determine if this patient has a persistent form of infection. In the case of a negative result for the presence of HPV, the interval between screening examinations may be 2.5 years or more. In addition, the authors do not recommend including the PCR method in a routine screening program, since in this case, too many cases of clinically insignificant infection are detected. Routine methods, in particular the PAP test, provide an adequate diagnosis, allowing the timely identification of groups of patients in need of treatment.

The study authors plan to continue monitoring study participants for 20 years from the screening visit to determine the frequency and timing of CIN development more than long-term stage 2 after l initial HPV infection.