In Brazil, according to data of the National Cancer Institute (Instituto Nacional de Câncer – INCA) (2015), cervical cancer is the most common cancer type among women of the North Region of the country, with an estimated risk of 23,97 cases per 100 thousand women. Many studies have shown that an infection by an HPV of high oncogenic risk, especially HPV-16 and 18, is closely related with the development of cervical cancer, with a higher chance of occurrence among HIV-positive women [9].
According to studies in the literature, HPV infection occurs in the first two consecutive years after first sexual intercourse, given that the incidence is higher among women below 25 years of age [13,22]. In the present study, among the group of HPV-infected women, the mean age was of 36 years, and infection was predominant among women of reproductive age, with a trend to reduced prevalence with increasing age. Similar data have been described in other Brazilian cities [23-25]. The results of the present study suggest that the reduced prevalence of infection in the group of women aged 39 years and above is due to marriage and, thus, reductions in both the number of partners and exposure to HPV.
Several epidemiological and reproductive health factors have been related with the development of cervical cancer, including HPV, smoking, genetic predisposition, number of sex partners, age of first sexual intercourse, parity, miscarriages and age at menarche [26] With respect to HPV infection, with the exception of immunosuppression caused by HIV, the literature is controversial with regard to establishing the risk factors for the acquisition of infection.
Studies on the general population of the North Region of Brazil have found diverging epidemiological associations between the examined population groups. In the Brazilian Eastern Amazon, there were strong associations between HPV infection and marital status, the use of condoms and the number of sex partners throughout life and in the past year [27]. The association between HPV infection and age range has been described in women of the general population, in female inmates in the Metropolitan Region of Belém [28] and in women in the municipality of Tomé-Açu [29].
Based on the results of the present study, even the regular use of condoms does not seem to provide total protection against microbial infection, given that the condom does not fully cover the male reproductive organ, hence leaving areas potentially harboring infectious particles or subclinical lesions, in the case of HPV, exposed during sexual intercourse. A history of multiple sex partners is an important risk factor for the acquisition of HPV because the higher the number of partners, the higher the odds of acquiring an infection by HPV and other STIs.
The innate immune system is known to have many protection mechanisms in the vaginal tissue against infections by pathogens, in part by ensuring the survival of the normal vaginal microbiota, which constitutes an important factor in the production of lactic acid and hydrogen peroxide, thus inhibiting pathogen growth. The acquisition of STIs promotes an imbalance in the vaginal microbiota, altering the pH and also possibly causing lesions in the lining epithelium of the cervix and vaginal wall. These changes might contribute to the development of inflammation and pathogen penetration, including HPV. In addition to the observed association between a previous history of STIs and HPV infection, the present study found that many women exhibited clinical features compatible with bacterial vaginosis, candidiasis and trichomoniasis, suggesting that the establishment of these infections might contribute to the acquisition and onset of HPV infection. Similar data have been reported by Grinsztejn et al [25] in Rio de Janeiro, whereas Gonçalves et al [30] found that age was the only variable associated with HPV infection in anogenital samples from HIV-positive women.
The global prevalence of HPV infection among HIV-1-positive women in the present study corroborates the findings of Gonçalves et al [30] but is lower than the rates observed in other Brazilian regions [24,31]. Among immunocompetent women of the North Region, the prevalence rate of HPV infection varies between 6%, 9% and 18% [27,29,32] showing that the incidence of HPV infection is high in the population of HIV-positive women.
The majority of HPV infections are clinically unapparent or asymptomatic in immunocompetent individuals [33,34]. However, the immunosuppression caused by HIV seems to favor infection by multiple HPV genotypes, which, if oncogenic, might contribute to the progression of intraepithelial lesions to CIN. According to Luque et al [35] the presence of multiple HPV genotypes in HIV-positive women is a poor indicator of prognosis in cases of CIN. In the present study, 49% (23/47) of the studied population exhibited infections by multiple genotypes, and, of these, 39.1% exhibited more than one high-risk genotype.
Previous studies have shown that the prevalence rates of lesions and CIN are higher among HIV-positive women compared to women from the general population [12,14,31,36,37] HIV infection is thought to change the natural history of HPV infection, favoring higher HPV persistence, reduced lesion regression rates and, consequently, progression to high-grade or invasive squamous intraepithelial lesions [38,39].
Some studies suggest that the persistence of HPV is inversely proportional to CD4+ T lymphocyte count and directly proportional to HIV viral load, which can also be influenced by ART [39-41]. However, there was no association between markers of HIV infection and HPV infection or between the different grades of intraepithelial lesions in the present study. These data corroborate other studies on HIV-positive women from the Southeast Region of Brazil [23,25]. Thus, it is suggested that ART is efficient in the maintenance of low levels of HIV replication, avoiding the abrupt depletion of CD4+ T lymphocyte levels. However, the effect of ART on the persistence of HPV infection has not yet been characterized in the literature due to the absence of studies on that topic.