Revista Adolescência e Saúde

Revista Oficial do Núcleo de Estudos da Saúde do Adolescente / UERJ

NESA Publicação oficial
ISSN: 2177-5281 (Online)

Vol. 15 nº 3 - Jul/Sep - 2018

Original Article Imprimir 

Páginas 44 a 51


Papanicolaou exams in teenagers and young women: cytological profile analysis

Examen de Papanicolaou en adolescentes y mujeres jóvenes: análisis del perfil citológico

Exame de papanicolaou em adolescentes e mulheres jovens: análise do perfil citológico

Autores: Katiuscia Baggio1; Brenda da Silva2; Marciele Oliveira Prestes3; Cassiano Diehl4; Michele Ferraz5; Janaina Coser6; Janice Pavan Zanella7

1. Graduated in Biomedicine by the University of Cruz Alta. Cruz Alta, RS, Brazil
2. Graduated in Biomedicine by the University of Cruz Alta, Student of the Post-Graduation Program in Comprehensive Health Care - Unicruz/Unijuí, Brazil
3. Graduated in Biomedicine by the University of Cruz Alta. Cruz Alta. Cruz Alta, RS, Brazil
4. Graduated in Biomedicine by the University of Cruz Alta. Cruz Alta. Cruz Alta, RS, Brazil
5. Doctor in Physics by the Department of Physics-Mathematics of the University of São Paulo. Post-doctorate in Statistics by the Department of Statistics by the University of São Paulo. São Paulo, SP, Brazil. Teacher at the Center for Health and Agrarian Sciences and Coordinator of the Applied Statistics Nucleus of UNICRUZ. Cruz Alta, RS, Brazil
6. raduated in Biomedicine by the University of Cruz Alta, RS. Doctorate in Cellular and Molecular Biology Applied to Health by the Lutheran University of Brazil (ULBRA). Canoas, RS, Brasil. Student of the Course of Biomedicine and Pharmacy of the University of Cruz Alta – Unicruz and also Post-Graduation Program in Comprehensive Health Care - Unicruz/Unijuí. Cruz Alta, RS, Brazil
7. Graduated in Pharmacy and Biochemistry from the Federal University of Santa María (UFSM). Santa María, RS, Brazil. Doctor en Biotechnology by the University of Caxias do Sul, RS. Student of the Biomedicine Course of the University of Cruz Alta – Unicruz y and also the Post-Graduation Program in Comprehensive Health Care - Unicruz/Unijuí. Cruz Alta, RS, Brazil

Janice Pavan Zanella
Universidade de Cruz Alta, Rodovia Municipal Jacob Della Méa, s/nº - Parada Benito
Cruz Alta - RS, Brasil. CEP: 98020-290
(janicezanella@yahoo.com.br)

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Keywords: Uterine cervical neoplasms, precancerous conditions, adolescent.
Palabra Clave: Neoplasias del cuello del útero, lesiones pre-cancerígenas, adolescente.
Descritores: Neoplasias do colo do útero, lesões pré-cancerosas, adolescente.

Abstract:
OBJECTIVE: This study aimed to determine the cytological profile of the uterine cervix of adolescents and young women who underwent cervical cancer screening at a public health service.
METHODS: This was a descriptive, analytical and retrospective study where were re-analysed 694 slides and requisitions reanalyzed from 103 adolescents between 12 to 18 years and young women from 19 to 24 years old. Data belong to a cytopathology school archive from 2013 to 2015. Data were tabulated and analyzed in the IBM SPSS statistical software version 22.
RESULTS: From the 103 analyzed slides, 93.2% were within the limits of normality and 13.1% had altered results with the presence of cellular atypia. In five cases of low grade squamous intraepithelial lesions / HPV, oral contraceptive were used by the youngsters. The most prevalent microbiota was Lactobacillus (52.4%), followed by Gardnerella vaginalis (35.9%).
CONCLUSION: The presence of squamous intraepithelial lesions in adolescents and young women shows a dynamic change in the cytological profile of this age group. The occurrence of cytopathologic changes in the young group may indicate the importance of monitoring or the inclusion of sexually active adolescents in the Uterine Cervical Cancer Control Program.

Resumen:
OBJETIVO: Este estudio tuvo como objetivo determinar el perfil citológico del cérvix uterino de adolescentes y mujeres jóvenes que realizaron el examen preventivo del cáncer del cuello del útero en un servicio de salud pública.
MÉTODOS: Se trató de un estudio descriptivo, analítico y retrospectivo en el cual se reexaminaron 103 láminas y requisiciones de exámenes citopatológicos de adolescentes en el grupo de edad de 12 a 18 años y mujeres jóvenes de 19 a 24 años de edad. Los datos proceden del archivo de un laboratorio escolar de citopatología en el período de 2013 a 2015. Los datos obtenidos fueron tabulados y analizados en el software estadístico IBM SPSS versión 22.
RESULTADOS: De las 103 láminas analizadas el 93,2% se presentaron dentro de los límites de la normalidad y el 13,1% tuvieron resultados alterados con presencia de atipias celulares. En cinco casos de lesiones intraepiteliales escamosas de bajo grado / VPH, se utilizaron anticonceptivos por las jóvenes. La microbiota prevalente fue la de Lactobacilos (52,4%), seguida de Gardnerellavaginalis (35,9%).
CONCLUSIÓN: La presencia de lesiones intraepiteliales escamosas en adolescentes y mujeres jóvenes evidencia un cambio dinámico en el perfil citológico de esa franja etaria. La ocurrencia de alteraciones citopatológicas observada en el grupo de edad más joven, puede indicar la importancia del monitoreo o la inclusión de las adolescentes sexualmente activas en el Programa de Control del Cáncer de Cuello Uterino.

Resumo:
OBJETIVO: Este estudo visou determinar o perfil citológico da cérvice uterina de adolescentes e mulheres jovens que realizaram o exame preventivo do câncer do colo do útero em um serviço de saúde pública.
MÉTODOS: Tratou-se de um estudo descritivo, analítico e retrospectivo no qual foram reanalisadas 103 lâminas e requisições de exames citopatológicos de adolescentes na faixa etária de 12 a 18 anos e mulheres jovens de 19 a 24 anos de idade. Os dados são provenientes do arquivo de um laboratório escola de citopatologia no período de 2013 a 2015. Os dados obtidos foram tabulados e analisados no software estatístico IBM SPSS versão 22.
RESULTADOS: Das 103 lâminas analisadas 93,2% apresentaram-se dentro dos limites da normalidade e 13,1% tiveram resultados alterados com presença de atipias celulares. Em cinco casos de lesões intraepiteliais escamosas de baixo grau/HPV, foram utilizados anticoncepcional pelas jovens. A microbiota prevalente foi a de Lactobacillus (52,4%), seguida de Gardnerella vaginalis (35,9%).
CONCLUSÃO: A presença de lesões intraepiteliais escamosas em adolescentes e mulheres jovens evidencia uma mudança dinâmica, no perfil citológico dessa faixa etária. A ocorrência de alterações citopatológicas observada no grupo etário mais jovem, pode indicar a importância do monitoramento ou a inclusão das adolescentes sexualmente ativas no Programa de Controle do Câncer de Colo Uterino.

INTRODUCTION

There are more than 1,800 million people in the world with ages between 10 and 24 years and in several countries sexual activity begins in late adolescence, generally between 15 to 19 years of age1. In Brazil there are approximately 36 million adolescents with up to 19 years of age, and 75% of these adolescents have an active sexual life2. It is important to note that there is a trend of increasingly early sexual initiation, mainly in developing countries such as Brazil. However, this condition can lead to an increase in the number of cases of human papillomavirus (HPV) infection and lesions resulting from this infection in this age group3.

Cervical cancer (CCU) is a chronic degenerative disease with a high degree of incidence that affects women in the reproductive age group. Despite being a neoplasm with great potential for prevention, it is still an important public health problem in Brazil, being the one that most cause's death among women aged between 15 and 44 years4. The CCU is a disease of slow evolution, presenting pre-invasive phases characterized by lesions called cervical intraepithelial neoplasms (CIN) or squamous intraepithelial lesions (SIL). These lesions, when diagnosed early, are amenable to cure4. The main risk factor for the development of high-grade intraepithelial lesions, which are precursor lesions and cervical cancer, is infection by the Human Papillomavirus (HPV). However, this infection alone doesn´t represent a sufficient cause for the appearance of neoplasia, where its persistence and the action of other cofactors are necessary5.

The tracking program of the CCU implanted in Brazil is done through the Papanicolaou exam, which includes women from 25 to 64 years old. The examination is simple and allows detecting alterations of the uterine cervix from desquamated cells of the epithelium. In addition, it is used in the diagnosis of cervico-vaginal infections associated or not with pathogens acquired via sexual transmission6.

The high prevalence of precursor lesions in women between 20 and 29 years of age also suggests the importance of the inclusion of sexually active adolescents in screening programs, since the occurrence of precursor lesions takes 10 to 15 years before invasive cancer. Women whose sexual activity begins in adolescence, have many sexual partners, are carriers of sexually transmitted infections and have various pregnancies in youth, statistically have a greater chance of developing cervical cancer.

Sexually active young adults, mainly at the beginning of sexual life, are the most exposed to the risk of contamination by HPV. Thus, the early onset of sexarca in young women without regular use of condoms favors the spread of various sexually transmitted infections (IST). This exposure benefits early contact with HPV and then infection with this agent. The presence of cytopathic effect of the virus in oncotic cytologies in young patients indicates this situation, since other agents are in association with HPV. This maintenance of active sexual life without due precautions cause's successive exposures to the various types of HPV7.

The incidence of HPV in adolescents was demonstrated in other studies8, revealing in a study carried out with 30,207 women between 17 and 59 years old, where 17.7% of them presented in the genotype molecular viral genetic material of high oncogenic risk.

The increase in the frequency of pre-neoplastic cervical lesions in adolescents and young women points to the need to study and investigate the behavior of these alterations in this age group, whose understanding may help the development of strategies and intervention mechanisms that reduce morbidity rates for this neoplasm. In this study, we aimed to establish the cytological profile of adolescents and young women treated in a public health service.


MATERIALS AND METHODS

A retrospective descriptive study of cervico-vaginal films and requisitions belonging to the collection of plates of the Cytopathology Laboratory of the Cruz Alta University, Cruz Alta - Rio Grande do Sul, related to the period from 2013 to 2015 was carried out. The research project was approved by the Research Ethics Committee of the University of Cruz Alta, under consubstantial opinion No. 1,596,248.

In this study, 103 sheets and requisitions were included for adolescents and young women, between the ages of 12 and 24, who underwent the Papanicolaou test in the public health network. The selected leaves were grouped by age group in two groups: one of 12 to 18 years and another of 19 to 24 years of age.

The sheets were reevaluated by three observers using Olympus optical microscope model CX31. The microbiota and cytological criteria to classify the results were evaluated based on the Bethesda System and categorized as: Within the Limits of Normality (DLN) when the squamous and endocervical glandular epithelial cells presented normal cellular characteristics; Atypical Squamous Cells of indeterminate significance (ASC) and Atypical Glandular Cells of Indeterminate Significance (AGC), when the cellular alterations found were more accentuated than the inflammatory and reactive ones, but insufficient to conclude a squamous or glandular intraepithelial lesion; Low-grade squamous intraepithelial lesion (LSIL) when the lesion affected mature squamous cells; High-grade intraepithelial lesion (HSIL), when the lesion includes cells of the most immature squamous tissue. In the case of HSIL, there were suspicions of microinvasion, in which the lesion in young cells already had invasion criteria(11).

Epidemiological information such as age, use of oral contraceptives and clinical examination (appearance of the neck) were evaluated based on the data contained in the examination request of each patient included in the study.

The data was tabulated and analyzed in the statistical software IBM SPSS version 2.2. The qualitative variables were described by their frequency (n) and percentage (%) distributions. The association and comparison of proportions between two qualitative variables were evaluated by the Pearson Chi-square test and the Fisher exact test (for expected values less than 5 and table 2x2). The level of significance adopted for the statistical tests was 5% (or p <0.05).


RESULTS

Of the 103 slides of adolescents and young women evaluated, 93.2% (96) were negative for intraepithelial lesion or malignancy (NILM), 13.1% (7) were altered with cellular atypia including pre-malignant intraepithelial lesions. Among the altered ones, 71.4% (05) had a low-grade squamous intraepithelial lesion (LSIL) / HPV, 14.2% (01) were classified as squamous atypia of undetermined significance (ASC-US), and 14,2% (01) as high-grade squamous intraepithelial lesion (HSIL). Table 1 presents the data of the distribution of cytological alterations obtained in each age group studied, in which it is visualized that the highest occurrence of ASC-US, LSIL / HPV and HSIL was found in the age group of 19 to 24 years.




Table 2 presents the cytological results in relation to the use of oral contraceptives, in which it was verified that adolescents with HPV infection were users of oral contraceptives. In the group aged 12 to 18 years, 6.1% women reported using the contraceptive and presented LSIL/HPV in the cytopathological examination. In the group of 19 to 24 years, 4.3% of the women indicated the use of contraceptives and presented LSIL/HPV and 1.4% used contraceptives and presented HSIL in the cytopathological examination.




No statistically significant association was found between the contraceptive use variable and both age groups analyzed (12 to 18 years, 19 to 24 years) (p = 0.489, p = 0.175, respectively). The cytopathological results referring to the cervicovaginal microbiota are described in Table 3, being possible to observe the predominance of Lactobacillus followed by Gardnerellavaginalis.




Fisher's exact test showed no significant difference in the presence or absence of bacilli between the ages of 12 to 18 years and 19 to 24 years (p = 0.751), as well as the presence or absence of Candidaspp, between ages from 12 to 18 years old and from 19 to 24 years old (p = 0.495). In most cases, the Chi-square test showed no difference in the presence or absence of lactobacilli (p = 0,899), of cocci (p = 0,320) and of Gardnerellavaginalis (p = 0,707) between the ages of 12 to 18 years and 19 to 24 years.

In relation to the clinical information on inspection of the cervix described in the requisitions, most of the patients presented a normal neck with the presence of benign alterations. In the age group of 19 to 24 years, the indication of an altered neck was associated with inflammation and immature metaplasia. In the age group of 12 to 18 years there was no altered neck (Table 4).




In the age group of 12 to 18 years, according to the Chi-square test, there was no statistically significant association between the variables benign alterations and inspection of the neck (p = 0.899) and between the age group of 19 to 24 years (p = 0.306).

When the inspection of the neck was related to the altered cytological results, it was observed that in the age group of 19 to 24 years there was the occurrence of three altered necks, where two were associated with NILM and one associated with ASC-US. In the age group of 12 to 18 years, there were two cases of LSIL/HPV without changes in the neck (Table 5).




According to the chi-square test, no statistically significant association was found between the inspection variable of the neck and the cytological results in the age ranges of 12 to 18 years (p = 0.611) and 19 to 24 years (p = 0.711).


DISCUSSION

With respect to the cytological results that were presented within the limits of normality, there is agreement with the study of Pias9 whose analysis of records showed 95.3% of normality. In the cases of ASC-US there was agreement with other authors, one of them being the study of 10 who analyzed cytological reports and obtained 1.04% of cases of atypia. Vargas, Gelatti and Buffon11 verified in their study that the diagnosis of ASCUS doesn´t remove the possibility of high-grade intraepithelial lesion, which corresponds to diagnoses with epithelial alterations of doubtful significance and that need better investigation.

For Moscicki12, cytological abnormalities, the consequences of HPV infection, present a small risk of neoplastic progression when diagnosed between three and five years after the onset of sexual activity. In this study, 10.4% of LSIL/HPV was observed, unlike the study by Silva et al., (2015) 6 who analyzed 331 records found 1.8% prevalence of this lesion.

According to Burchell13, the prevalence of HPV infection in younger women is 3-4 times higher than in women aged 35 to 55 years, with the trend of declining the curve in older age groups. For Schlecht14 the cumulative risk of infection decreases from 43% in women between 15-19 years of age to 12% in women of 45 years of age. These authors also report that the alterations frequently found in adolescents are of low grade lesions, which most of the time, regress spontaneously even without treatment. However, the risk of progression for high-grade lesion and carcinoma can not be ignored if these lesions caused by high-risk HPV aren´t treated14.

It also highlights the importance of screening policies for cervical lesions in women in this younger age group, thus avoiding the progression of lesions that progress to cancer, since in this study 10.4% of LSIL/HPV and 1,4% of HSIL occurred in women under 25 years of age.

A consistent relationship between oral contraceptive use and cervical neoplasia isn´t yet established. In this study, most women used oral contraceptives. Murta and colleagues (2001) suggest that the contraceptive would act as a cofactor, along with genetic alterations and some types of HPV, in the transformation of cells and in the progression of lesions from low to high grade. A retrospective study that analyzed the use of oral contraception in 6,498 adolescents with HPV infection, showed that 326 of them had alterations compatible with viral infection, associated or not with LSIL and 47 cases of HSIL. The number of adolescents in the group with HPV infection and oral contraceptive users was higher when compared to the control group without HPV infection11.

In adolescence, cervical biological activity is at the maximum level. In this phase, cellular replication and substances present in the cervical environment facilitate HPV infection. After adolescence, the frequency of infection in women decreases with age14. In addition to that, Panissety Fonseca15indicates that the adolescent cervix, most of the time, presents ectopia and immature transformation zone. This eversion process exposes the glandular mucosa, which, being more fragile, suffers aggression of the acidic pH of the vaginal environment, of microorganisms and/or traumas, contributing to the development of chronic inflammatory processes in the cervix. The presence of cervical ectopia can be considered a risk factor for several IST, with HPV infection being one of the most common. This occurs because, from micro cracks, HPV can reach basal cells and initiate the process of viral replication and the development of pre-neoplastic or neoplastic cervical lesions16.

Infections associated with HPV in young women have been linked to factors such as multiple sexual partners, age, and early onset of sexual activity, smoking and oral contraceptive use. Although the spontaneous elimination of the virus is frequent in younger women, the resolution capacity decreases the higher the age group17.

The vagina and the cervix are commonly inhabited by various species of aerobic and anaerobic bacteria that constitute a complex ecosystem. Under conditions in which there are variations in vaginal pH, decreased immunity, diabetes and iatrogenic factors, there may be an imbalance in the microbiota, which may result in infections/inflammation18. According to Leitão18, Lactobacillus, cocci and Bacillus are part of the vaginal microbiota, so their presence is considered normal, and they don´t characterize the infection. In this study, without considering the lactobacillary flora, Gardnerellavaginalis was the most prevalent infectious agent (35.9%). A Gardnerella vaginalises is one of the bacteria involved in the pathophysiology of bacterial vaginosis and is more commonly found in women with cytopathological lesions8.

At the time of collection of cervical material, with the help of a device called a speculum, it is possible to perform a visual inspection of the vagina and cervix and make a first evaluation. Some observed characteristics may be related, for example, the presence and appearance of vaginal secretions, coloration and appearance of the neck surface, epithelization and shape of the external orifice, and its observation is of great importance for an initial evaluation of the woman, it provides visual subsidies on the presence of possible cervical alterations. This observation is so important that the National Cervical Cancer Control Program included in the examination request a specific field for the description of these characteristics, also stressing that "In the presence of an altered neck, with a lesion suggestive of cancer, don´t wait for the result of the cytopathological examination to direct the woman to colposcopy ", that is, for complementary examination of the diagnostic tripod of this neoplasia (cytology-colposcopy-histology). In addition, this information is essential for the cytologist, since they are additional information of the patient that can consubstanciar the classification of the cytological material19.

In this study, it was observed that 10.4% of women presented with an altered cervix, and only one was associated with ASC-US in cytology. Corroborating with these findings, Anjos et al.20 described in their study that "it isn´t possible to directly relate this factor to cervical lesions, since certain women have abnormalities in the cervix and not necessarily the lesions".

Thus, the results of the research indicate that the age group with the most cervical lesions was 19 to 24 years old and that the use of oral contraceptives was related to all cases of LSIL / HPV. The prevalence of the microorganisms that cause IST, as well as the occurrence of cervical lesions in the adolescents and younger women obtained in this study has a discordant position in the literature that shows the absence of more serious injuries in this age group. However, it is important to highlight the case of HSIL in a young woman (23 years old) identified in our research.

This study serves as an alert to discuss the inclusion of adolescents and younger women in the programs of tracking or monitoring of precursor lesions of cervical cancer, once the rate of occurrence of these cytological alterations has been increasing in these groups. We emphasize the importance of epidemiological and cytopathological data of adolescents and young women to help health managers in the improvement, targeting and strategies of health services aimed at these groups, in order to correct the distortions of the care that occurs in a fragmented, disjointed with isolated strategies and actions without respect for the integrality of attention.


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