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Vol. 39. Issue 4.
Pages 297-302 (October - December 2019)
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Vol. 39. Issue 4.
Pages 297-302 (October - December 2019)
Original Article
DOI: 10.1016/j.jcol.2019.05.013
Open Access
Profile of women with anal neoplasia associated with cervical neoplasia receiving care at a tertiary healthcare facility in northeastern Brazil
Perfil de mulheres com neoplasia anal associada à neoplasia cervical atendidas em um serviço de saúde terciário do nordeste do Brasil
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Gian Francisco Almeida, Sandra Heráclio
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sandraheraclio@gmail.com

Corresponding author.
, Alex Sandro Rolland Souza, Melania M. Amorim
Instituto de Medicina Integral Prof. Fernando Figueira (IMIP), Programa de Pós-graduação em Saúde Integral, Recife, PE, Brazil
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Tables (4)
Table 1. Biological and sociodemographic characteristics of the women with cervical and anal neoplasia (n=181).
Table 2. Sexual, reproductive and behavioral characteristics of the women with cervical and anal neoplasia (n=181).
Table 3. Clinical and laboratory characteristics of the women with cervical and anal neoplasia (n=181).
Table 4. Frequency distribution of the anal cytology, colposcopy and histopathology results (n=181).
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Abstract
Objective

To describe the epidemiological, clinical and laboratory profiles of women with anal neoplasia associated with cervical neoplasia attending a tertiary healthcare facility in northeastern Brazil.

Methods

This epidemiological, descriptive study was conducted using a database from a cross-sectional study carried out between December 2008 and January 2016. Women with a diagnosis of cervical neoplasia associated with anal neoplasia were included in the present study.

Results

Of the women with cervical neoplasia, 14% were found to have an anal intraepithelial lesion or anal cancer. Median age was 33 years, 68% were non-white, and 70% were from urban regions, had little schooling and low income. Most reported having had anoreceptive (73%) and unprotected intercourse (84%). Regarding symptoms, 7% reported bleeding and 11% pruritus. Overall, 10% of the sample tested positive for the human immunodeficiency virus. Anal cytology was abnormal in 92%. High-resolution anoscopy was abnormal in all cases. Histopathology revealed three cases of invasive carcinoma and high-grade lesions in 32% of the cases.

Conclusion

Women with a diagnosis of anal and cervical neoplasia are often young, non-white women, who initiated their sexual life at an early age, were exposed to unprotected anoreceptive intercourse, live in urban centers, have little schooling and a low-income level.

Keywords:
Papillomavirus infections
Cervical neoplasia
Diagnosis
Anal neoplasia
Resumo
Objetivo

Descrever os perfis epidemiológico, clínico e laboratorial de mulheres com neoplasia anal associada à neoplasia cervical atendidas em uma unidade de saúde terciária no nordeste do Brasil.

Métodos

Este estudo epidemiológico e descritivo usou um banco de dados de um estudo transversal realizado entre dezembro de 2008 e janeiro de 2016. Mulheres com diagnóstico de neoplasia cervical associada à neoplasia anal foram incluídas no presente estudo.

Resultados

Das mulheres com neoplasia cervical, 14% apresentaram lesão intra-epitelial anal ou câncer anal. A mediana de idade foi de 33 anos; 68% das pacientes não eram brancas e 70% eram provenientes de regiões urbanas, com baixa escolaridade e baixa renda. A maioria relatou histórico de relações sexuais anoreceptivas (73%) e desprotegidas (84%). Quanto aos sintomas, 7% relataram sangramento e 11% prurido. No geral, 10% das pacientes apresentaram serologia positiva para o vírus da imunodeficiência humana. A citologia anal foi anormal em 92% da amostra. A anuscopia de alta resolução foi anormal em todos os casos. A histopatologia revelou três casos de carcinoma invasivo e lesões de alto grau em 32% dos casos.

Conclusão

As mulheres com diagnóstico de neoplasia anal e cervical geralmente são jovens, não brancas, que iniciaram sua vida sexual em idade precoce, foram expostas a relações sexuais anoreceptivas desprotegidas, moram em centros urbanos e têm baixa escolaridade e baixo nível de renda.

Palavras-chave:
Infecções por papilomavírus
Neoplasia cervical
Diagnóstico
Neoplasia anal
Full Text
Introduction

Human Papillomavirus (HPV) is the agent responsible for over 90% of cases of anal and cervical cancer.1 More than 40 HPV subtypes have tissue tropism for the anogenital tract.2 The same oncogenic HPV subtypes that lead to cervical intraepithelial lesions are also associated with anal intraepithelial lesions, which are precursors of anal canal cancer.3 These subtypes of HPV act by promoting the development of lesions in the transitional zone in the junctional epithelium of the anal canal.4

Despite being one of the less common forms of gastrointestinal cancer, the attention paid to anal and anal canal cancer has increased over recent decades due to the rise in their incidence, particularly in women.5 Around 8000 new cases of anal cancer were estimated to occur in the United States in 2015, with the frequency being higher among women compared to men.6 Furthermore, estimates indicate that over 34,000 new cases of HPV-associated anal intraepithelial neoplasia occur each year.7

The incidence of precursor lesions and squamous cell carcinoma of the anus is highest among HIV-positive individuals and men who have sex with men. However, for these groups, guidelines for anal dysplasia screening are already in place.8 On the other hand, women with genital neoplasia, solid organ transplantation recipients and individuals submitted to chronic immunosuppression for various diseases are also at a significantly increased risk of neoplastic precursor lesions of the anal canal.9,10 Consequently, screening for precursor lesions has been encouraged in these groups.11–13 Nevertheless, there is a need for further investigation into the profile of the women affected by this disease, since few studies have been conducted in this population.

The objective of the present study was to describe the epidemiological, clinical and laboratory profile of women with anal neoplasia associated with cervical neoplasia attending a tertiary healthcare facility in Recife, Pernambuco, a state of northeastern Brazil.

Methods

A descriptive, epidemiological study was conducted based on a database from a cross-sectional, observational study conducted between December 2008 and January 2016. The original study included all the women attending the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) with a histopathology diagnosis of cervical intraepithelial neoplasia or cervical cancer. Women undergoing radiotherapy or chemotherapy were excluded from the study, as well as those suffering from mental illness, incarcerated women and those known to be HIV-positive.

The women who fulfilled all the eligibility criteria were included in the study if they voluntarily agreed to participate and signed an informed consent form. The institute's internal review board approved the protocol of the original study under reference number CAAE 0230.0.099.000-11.

The participants answered an epidemiological questionnaire, underwent gynecological examination and were screened for Sexually Transmitted Infections (STIs). An Enzyme-Linked Immunosorbent Assay (ELISA) was used to test for HIV, VDRL was used to test for syphilis, and antibody testing was conducted for hepatitis B and C. In addition, brush specimens were collected for anal cytology, High-Resolution Anoscopy (HRA) was performed, and biopsy was carried out whenever indicated. The same professional performed all the procedures throughout the entire study period.

Anal cytology was conducted using an endocervical brush moistened in saline solution and introduced up to 4cm from the anal verge. The slides were fixed in 96% ethanol, stained using the Papanicolaou technique and classified according to the Bethesda system terminology.14

HRA was performed following inspection of the perianal region, digital rectal examination, anoscopy and application of 5% acetic acid and Lugol's iodine solution, with colposcopic evaluation of the transitional zone of the anal canal. The classification used was that of the Brazilian Association of Genitoscopy (Barcelona Consensus, 2002).15 The lesions identified at HRA were biopsied in the clinic under local anesthesia, except for lesions associated with large prolapsed hemorrhoids, which were managed by a proctologist.

Results

A total of 1242 women with a histopathological diagnosis of cervical intraepithelial neoplasia or cervical cancer were screened for anal intraepithelial lesions. Of these, 14% (n=181) were diagnosed with anal intraepithelial neoplasia or anal cancer. In relation to the biological and sociodemographic characteristics of this subgroup, 56% were over 35 years of age, with a median age of 33 years (range 16–75 years); 68% were non-white; the majority (72%) lived in an urban center and 70% reported a family income of no more than one minimum salary. Median education level consisted of 6 years of schooling (range 0–13 years), with 63% of the women in the study having between 0 and 7 years of schooling (Table 1).

Table 1.

Biological and sociodemographic characteristics of the women with cervical and anal neoplasia (n=181).

Characteristics  n 
Age
0–35 years  79  43.6 
≥36 years  102  56.4 
Skin color
White  58  32.0 
Non-white  123  68.0 
Family income
≤1 minimum salary  126  69.6 
>1 minimum salary  55  30.4 
Schooling
0–7 years  114  63.0 
≥8 years  67  37.0 
Area of residence
Rural  51  28.2 
Urban  130  71.8 
Marital status
With a stable partner  100  55.2 
No stable partner  81  44.8 

Regarding their sexual, reproductive and behavioral characteristics, median age at sexual debut was 16 years (range 8–30 years); 73% reported having had anoreceptive intercourse and most reported having first had anal intercourse before completing 30 years of age. Few used condoms (16%) and only 11% reported having had genital warts. Median parity was 2 (range 0–9) (Table 2).

Table 2.

Sexual, reproductive and behavioral characteristics of the women with cervical and anal neoplasia (n=181).

Characteristics  n 
Age at first sexual intercourse
≤16 years  91  50.3 
≥17 years  90  49.7 
Number of partners
1–4  117  64.6 
≥5  64  35.4 
Anal intercourse
Yes  132  72.9 
No  49  27.1 
Age at first anal intercourse (n=132)
≤30 years  115  87.1 
≥31 years  17  12.9 
History of genital warts
Yes  20  11.0 
No  161  89.0 
Use of the oral contraceptive pill
Yes  59  32.6 
No  122  67.4 
Use of condoms
Yes  29  16.0 
No  152  84.0 
Parity
0–2  109  60.2 
≥3  72  39.8 
Smoker
Yes  41  22.7 
No  140  77.3 
Consumes alcohol
Yes  79  43.6 
No  102  56.4 

Proctologic diseases in general were present in 69% of cases. Anal skin tags were the most common finding (63%) followed by hemorrhoids (26%). Anal bleeding was reported by 7% of the women and pruritus by 11%. ELISA for HIV was positive in 10% of the patients, while VDRL was positive in 2%. None of the women tested positive for hepatitis B or C (Table 3).

Table 3.

Clinical and laboratory characteristics of the women with cervical and anal neoplasia (n=181).

Characteristics  n 
Anal disorders
Yes  124  68.5 
No  57  31.5 
Hemorrhoids
Yes  47  26.0 
No  134  74.0 
Anal skin tag
Yes  114  63.0 
No  67  37.0 
Anal fissure
Yes  1.1 
No  179  98.9 
Fistula
Yes 
No  181  100 
Bleeding
Yes  12  6.7 
No  164  90.6 
Data missing  2.7 
Pruritus
Yes  19  10.5 
No  157  86.8 
Data missing  2.8 
ELISA for HIV
Positive  18  9.9 
Negative  163  90.1 
VDRL
Yes  1.6 
No  177  97.8 
Not performed  0.6 
Hepatitis B and C
Positive 
Negative  179  98.9 
Not performed  1.1 

Regarding the results of the anal Pap smears, 92% were abnormal, consisting of atypical squamous cells of undetermined significance in 15%, low-grade intraepithelial lesions in 53% and high-grade intraepithelial lesions in 24%. HRA was abnormal in all cases, with acetowhite epithelium being found in 89% of cases and constituting the most common abnormality. Histopathology revealed HPV infection in 25% of cases, low-grade intraepithelial lesion in 41%, high-grade intraepithelial lesion in 32% and three cases of invasive carcinoma (Table 4).

Table 4.

Frequency distribution of the anal cytology, colposcopy and histopathology results (n=181).

Cytology  n 
Within normal parameters  13  7.2 
Atypical squamous cells of undetermined significance  27  14.9 
Low-grade intraepithelial lesion  96  53.0 
High-grade intraepithelial lesion  44  24.3 
Unsatisfactory  0.6 
High-resolution anoscopy
Acetowhite epithelium  162  89.5 
Mosaic  1.1 
Punctation  0.6 
Verrucous lesions  2.8 
Association of images  11  6.1 
Anal histopathology
HPV infection  46  25.4 
Anal intraepithelial neoplasia grade 1  75  41.4 
Anal intraepithelial neoplasia grade 2  34  18.8 
Anal intraepithelial neoplasia grade 3  23  12.7 
Invasive carcinoma  1.7 
Discussion

The present sample of women with anal and genital neoplasia consisted mainly of young, poor, non-white women with little schooling, living in urban centers. This profile resembles that of users of the Brazilian National Health Service in this region and reflects the degree of social inequality that exists in our urban centers,16 a fact that has also been reported in other studies.17,18 These are women who begin their sexual life at an early age and who have unprotected sex, including unprotected anal intercourse.18–20 Because HPV infection is an STI, unprotected sex is a risk factor for HPV infection, which in turn increases the risk of an invasive lesion both in the female genital organs and in the anal canal.20 The population in general should be made aware of this fact, and women, in particular, should be empowered, since those in situations of greater vulnerability often find it difficult to negotiate condom use with their partner.

The high levels of alcohol consumption and smoking (44% and 23%, respectively) found here are factors that have already been reported as being associated with the development of neoplasia.21 Public health policies aimed at reducing and controlling smoking and alcohol consumption do exist. The prevention of various neoplasms, including HPV-associated neoplasia, should be at the core of these programs.

Symptoms such as bleeding, pruritus and even anal pain are present in only around 15% of cases of anal neoplasia, irrespective of sex, sexual habits or the grade of the lesion found.22 All of these symptoms except for anal pain were reported in the present study. Nevertheless, since such lesions are often asymptomatic, consideration is being given to proposing new ways of alerting the population and to making screening broader-reaching and effective, particularly for higher-risk groups such as women with cervical intraepithelial lesions and invasive cervical cancer.

STIs such as Neisseria gonorrhea, Chlamydia trachomatis, Trichomonas vaginalis, syphilis, herpes simplex virus 2 and HPV have been shown to play an important role in the acquisition of HIV.23 This evidence supports the recommendation to test women with an HPV infection for other STIs, particularly HIV and syphilis. In this sample of women, 10% tested positive for HIV, a fact previously unknown, since a prior diagnosis of HIV was one of the exclusion criteria established for this study. Because this population has been found to be vulnerable, the practice has now been adopted in this institute to routinely investigate for STIs.

Anal cytology screening is the most common method used to screen for anal cancer precursor lesions in high-risk individuals, with an effectiveness that is similar to that found for cervical cytology.8 The sensitivity of anal cytology ranges from 42% to 98%, with specificity of 32% to 96%.24 As expected, the majority of cytology tests were abnormal in the sample investigated in the present study, since this was a subgroup of patients with anal lesions. However, these results suggest that anal cytology is sensitive enough for the detection of HPV-induced anal lesions in women with cervical neoplasia.

Cytology screening identifies those patients, in whom a further, more detailed investigation is warranted, contributing toward the early diagnosis and treatment of precursor lesions. Considering the substantial reduction in cervical cancer-associated morbidity and mortality in developed countries following the implementation of population-based screening programs25,26 and bearing in mind the similarities that exist between the cervix and the anal canal,4 it is reasonable to assume that screening programs for anal neoplasia in risk groups could reduce the incidence of anal cancer and increase survival rates as a function of early diagnosis and treatment.

Histopathology revealed that HPV-related lesions and low-grade lesions, respectively, were the most common findings; however, 30% of cases consisted of high-grade lesions and there were three cases of invasive cancer. Therefore, screening for anal lesions in patients with cervical intraepithelial neoplasia or cervical cancer is crucial for preventing progression to invasive squamous cell carcinoma, since prognosis is inversely proportional to staging at the time of diagnosis.27

These results serve to reinforce the need for further studies in the country on this subject and to highlight the importance of systematic screening for anal lesions in women with cervical neoplasia,24 which should be incorporated into the Brazilian government's national policy for women's comprehensive healthcare.28 In addition, these findings emphasize the magnitude of the problem of HPV infection, including the potential development of anal intraepithelial lesions and anal cancer, and should serve to encourage health departments to increase the number of awareness campaigns and HPV vaccination programs.

Conclusion

Women with a diagnosis of anal neoplasia associated with cervical neoplasia are often young, non-white women living in urban centers, with low incomes and poor schooling. They begin their sexual life early, have anoreceptive sex and do not use condoms. They come from regions where the availability of public services is often deficient. In view of these characteristics, these are the women who would benefit most from educational measures, vaccination and early screening for anal lesions.

Funding

Instituto de Medicina Integral Prof. Fernando Figueira (IMIP).

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgements

We proudly acknowledge UNIFACISA and IMIP, for promoting qualified public health care and high quality research in Northeast Brazil.

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