How to cite this article: González-López S, Martínez-Silva MG, Hernández-Hernández DM, Aguilar-Lemarroy A, Jave-Suárez LF. Frequency of cervical epithelial lesions reported in the Regional Laboratory of Exfoliative Cytology in Jalisco. Rev Med Inst Mex Seguro Soc. 2015;53 Supl 2:S132-9.
Received: October 22nd 2014
Accepted: May 15th 2015
Sergio González-López,a María G. Martínez-Silva,b Dulce M. Hernández-Hernández,c Adriana Aguilar-Lemarroy,d Luis Felipe Jave-Suárezd
aLaboratorio Regional de Citología Exfoliativa
bDepartamento de Anatomía Patológica, Hospital de Especialidades, Centro Médico Nacional de Occidente
cDivisión de Mejora a la Gestión de los Servicios de Salud, Coordinación de Políticas en Salud, Unidad de Educación, Investigación y Políticas de Salud, Instituto Mexicano del Seguro Social, Distrito Federal, México
dDivisión de Inmunología, Centro de Investigación Biomédica de Occidente
a,b,dInstituto Mexicano del Seguro Social, Guadalajara, Jalisco, México
Communication with: Luis Felipe Jave-Suárez
Telephone:(333) 3617 0060, extensión 31926
Background: The Official Mexican Norm for the prevention, treatment and control of Cervical Cancer (CC) indicates that the Papanicolau (Pap) is the procedure for the detection of this neoplasia; therefore, it is of interest to know the prevalence of suspected cases by this technique in Mexican population. In this study, we show the diagnosed cases in the State of Jalisco, México.
Methods: A retrospective study was made to the samples that arrived for their analysis to the Laboratorio Regional de Citología Exfoliativa (LARCE), of the Instituto Mexicano del Seguro Social (IMSS) in Guadalajara, Jalisco. We considered all cases from January 2010 to December 2012.
Results: We analyzed 188 095 cases, from which 5.3 % had a diagnosis of low dysplasia, 0.18 % of moderated dysplasia and 0.05 % of high dysplasia. Microinvasive and invasive cancer showed a low frequency (0.03 %).
Conclusions: The frequency of abnormal findings identified by vaginal cervical cytology is relatively low. The number of inadequate and limited samples for cytological assessment is high; there is a high proportion of women attending for the first time in life to cytology evaluation in older age groups.
Keywords: Screening, Cytology, Cervical intraepithelial neoplasia, Mexico.
Cervical cancer is the third most common cancer in women worldwide, with an estimated 530,000 new cases just in 2008. In epidemiological terms, developing countries have a higher incidence of this disease, bringing more than 85% of the total and representing 13% of all cancers in women with a mortality rate of 52%. In connection with this last figure, the countries of Latin America and the Caribbean totaled 31,400 deaths from CC.1 In our country, the average incidence in 2008 was estimated at 10,186 new cases and 5601 deaths,2 so this disease has remained the leading cause of death in women over age 25.3 Cervical Cancer represents a serious social problem, since approximately 30% of women diagnosed are of reproductive age and 3% are pregnant.4
The main etiologic factor of cervical cancer is infection with the human papillomavirus (HPV);5 there are more than 100 types of HPV classified as low- or high-risk according to their oncogenic potential. About 30 of them are related to anogenital cancers, and infection of some of them (about 14 types) has been described as high-risk because they promote the development of cervical carcinogenesis.6 HPV infection in cells of the basal membrane can cause cervical intraepithelial neoplasia (CIN), which are subclassified into three grades according to their degree of involvement: CIN I (mild dysplasia), CIN II (moderate dysplasia) and CIN III (severe dysplasia). CIN I lesions belong to the group of LSIL (low squamous intraepithelial lesions), while CIN II and CIN III lesions are considered HSIL (high squamous intraepithelial lesions).7,8 Tumorigenesis is a slow process and can be regressive (usually to CIN II), and progression to cancer can take decades.9 When cancer cells break the basal membrane, they can access blood or lymphatic vessels and metastasize to other organs. Cervical cytology has been widely used as a screening test in cervical cancer prevention programs.10 The test was introduced by Papanicolaou in 1941, and widespread implementation in the following years led to a dramatic decrease in CC incidence rates. In recent decades, cytology screening programs have substantially reduced the incidence and mortality of cervical cancer in developed countries. For example, in the United States the incidence of invasive cancer in 1975 was 14.8 per 100,000 women; in 2006, that figure fell to 6.5 per 100,000 women, thanks to early screening programs.11 However, the success of cytology in reducing the incidence of cervical cancer has not been reproduced successfully in middle- to low-income countries, where despite a decrease in the observed incidence, this decline is still far from the figures obtained by developed countries.
In the Instituto Mexicano del Seguro Social (IMSS) a cervical cancer prevention and control program was implemented in 1973 and, after almost 20 years of application, the rate observed in 2002 amounted to 14.1 per 100,000 women; following program restructuring and consolidation, the mortality rate of this disease was reduced to 8.9 per 100,000 women in 2005.12,13 Despite the reduction of the incidence rates of the disease, the values obtained are still relatively high, so currently CC remains a major cause of death in women in our country. The same phenomenon is observed in low- to middle-income countries.14,15 These data lead us to question not only the effectiveness of cytology as a screening method, but also the efficiency of early detection programs in these countries. Cervical cytology has shown success in reducing the incidence of CC; but despite this, it is estimated that 50% of women diagnosed with CC had never had a cytological test done, and of those who had had cytology, 10% had not had it done in the past five years.16,17 This demonstrates that the absence of screening is a major risk factor for the lack of early detection of CC.
In 1994 Mexico established the Norma Oficial Mexicana for the prevention, treatment, and control of cervical cancer, which states that Papanicolaou cytology (Pap) is the procedure of choice for the early detection of this malignancy. The Programa Nacional para la Detección Oportuna del Cáncer Cérvico Uterino (National Program for Early Detection of Cervical Cancer) in Mexico is offered annually to women aged 25 to 64 and is an integral part of health services, but the infrastructure is insufficient to serve the entire female population of the country.18
This study analyzed the results of cervical cytology for the years 2010, 2011, and 2012 that were sent for evaluation to Laboratorio Regional de Citología Exfoliativa (LARCE), which receives samples from around the state of Jalisco. This was done in order to determine the prevalence of suspected cases of cervical cancer and precancerous lesions, evaluated by exfoliative cytology in women insured by IMSS from the state of Jalisco who were included in the cervical cancer early detection program.
A retrospective, cross-sectional, descriptive, and observational study was done of patients undergoing early detection for cervical cancer in the LARCE of IMSS in Guadalajara, Jalisco; all cases from January 2010 to December 2012 were considered.
The information was obtained from cervical cytology sheets containing the data considered important, such as age, district of origin, the instrument with which the sample was taken, sample quality, cytological diagnosis, first or subsequent cervical cytology, gyneco-obstetric situation at the time of sample, macroscopic observation of the cervix, and additional findings. The LARCE receives a high rate of annual cytology; moreover, its population is representative of urban women, allowing the findings to be extrapolated.
Women of any age were included who had a Pap sample taken that was properly identified and labeled. The study excluded broken cytology slides or those without corresponding labels.
The variables analyzed were age and cytological diagnosis (cytology without lesion, inflammatory, mild, moderate, and severe dysplasia, as well as in situ or invasive carcinoma).
The total population who underwent Pap cytology was included; there were 188,065 total cases.
The data were collected in the program Microsoft Excel 2010. Then they were put into to the program PASW Statistics, version 18, for analysis. The qualitative variables are expressed according to their frequency and proportion. Some variables were grouped for ease of presentation.
To do this investigation, results were collected from the LARCE database retrospectively, without disclosing the identity of the women in the study, so the study has been listed as safe and has no conflicts of interest.
During the period from January 2010 to December 2012, 188,065 cervical smears were interpreted in the IMSS LARCE. The instrument most frequently used to take the sample was modified Ayre spatula and swab (92%). With regard to the quality of the sampling, 2.83% of all samples were invalidated due to being considered inadequate for cytological interpretation, and 97.13% were considered of adequate and limited quality. 72.58% of the samples were reported as "adequate" (those with endocervical cells or squamous metaplasia), which remained at the same percentage during the three years of study; and 24.46% were considered "limited" (samples without endocervical cells or squamous metaplasia), with an increase of 7.61% over the three-year period. Samples inadequate for cytologic interpretation in 2010 accounted for 7.24% of all samples, which decreased to 0.12% in 2012. This represented a decrease of 98.3%. However, the percentage of samples of limited quality, which in 2010 was 19.78%, increased to 27.39% in 2012 (Table I). According to cytological report, of the 188,065 samples, the inflammatory process predominated in 92.44%, followed by 5.29% of mild dysplasia, 0.18% moderate dysplasia, 0.05% severe dysplasia, and 0.03% probable cervical carcinomas. Cytologies considered without lesion were 1.97% (Table II).
|Table I Quality of sampling and cytological interpretation in 188,065 cases in study|
|Samples with result: adequate and limited quality||57,619||92.64||64,058||98.60||66,418||99.87||62,698||97.03|
|Samples with endocervical cells or squamous metaplasia: adequate quality||45,316||72.86||47,021||72.37||48,203||72.48||46,846||72.57|
|Samples without endocervical cells or squamous metaplasia: limited quality||12,303||19.78||17,037||26.22||18,215||27.39||15,851||24.46|
|Samples inadequate for cytological interpretation||4501||7.24||905||1.39||81||0.12||1829||2.91|
|Table II Cytological diagnosis derived from 188,065 samples|
Of all cases analyzed, regardless of age, 5 to 6% suggested HPV infection, taking into account their cytological features. It is worth noting that by age group, the group that presented the highest percentage of suggested HPV infection cases was 35-44 years, which coincides with the group in which the most cases of invasive cervical cancer are seen, which, together with the 45-59 age group, appear as the most vulnerable groups for cases of precancerous lesions and cervical cancer.
Regardless of cytological report, the age group that most frequently went to get tested was between 45 and 59 years of age (31 to 33% of women diagnosed), followed by the age group of 35 to 44 years (25 to 26%), and 25 to 34 years (23-24%). As shown in Figure 1, this pattern was similar during the years 2010, 2011, and 2012. Interestingly, in this analysis it can be seen that after age 59 there is a drastic decrease in the number of patients who come for cytology; that number is only 7% of all tests. This percentage decreases even more after age 65 (3 to 4%).
Figure 1 Percentage of age ranges of women going for Pap tests during the years 2010, 2011, and 2012
Another interesting finding is that, of the samples with dysplasia, those reported as mild (CIN I) occurred more often between 35 and 59 years, while after age 60 those decreased significantly (Figure 2). On the other hand, the samples diagnosed as CIN II and CIN III peaked between ages 45 and 59.
Figure 2 Cumulative percentages of cases diagnosed with mild (CIN I), moderate (CIN II), and severe dysplasia (CIN III) during the years 2010, 2011, and 2012
Considering all stages of CIN as premalignant lesions (PL), we can see that the percentage of PL in the lowest age range was between 4 and 6% between 2010 and 2012. It should be noted that this percentage increases with age and peaks in the 35-44 age range, where we can see an incidence of up to 7.4%. In the older age ranges, the percentage of PL decreases to a range of 2-4% at ages 60 or older (Figure 3).
Figure 3 Percentage of cases diagnosed with precancerous lesions (PL), regardless of the degree of malignancy, plotted by age range groups during the years 2010, 2011, and 2012
The patients undergoing cytology were asked if it was the first time in their life that they had a test of this type, or if they had already had a previous test (1, 2, or 3 years or more). On this basis they were classified as first-time or subsequent patients. As shown in Figure 4, in both groups, first-time and subsequent, in the years 2010, 2011, and 2012, an expected pattern was observed in the age ranges < 25 and 25 to 34, with more first-time patients, which tends to decrease with increasing age. However, in higher age ranges (above age 35) it was expected that the number of first-time patients would decrease drastically, which did not happen. Our data indicate that there was an almost equal number of first-time patients, compared with subsequent patients, in the age groups ranging between 35 and 59 years of age; even in the age range over 59 years there was a considerable number of first-time cytology patients, which is a clear indication that patients come late to have cytology performed.
Figure 4 Number of first-time and subsequent cases, plotted by age group and regardless of diagnosis, during the years 2010, 2011, and 2012
When analyzing the prevalence of premalignant lesions and cervical cancer in the population captured by the LARCE, it was seen that the highest prevalence of LSIL was in the 35-44 age group with 7.03% in 2010, 5.5% in 2011, and 6.16% in 2012. The group with the lowest prevalence of low-grade lesions was 65 years or more. As for HSIL, the opposite was observed: the group of 65 years or more presented the highest prevalence, at least in the years 2010 and 2011, since in 2012 the 60 to 64 age group had a higher HSIL prevalence. Importantly, although the standard says that cytology should be done starting at age 25, LARCE receives cytology patients under 25 for evaluation; the cytologies of patients under 25 years found a prevalence of LSIL in the range of 4.0 to 5.7% and HSIL between 0.14 and 0.42%, in the three years studied (Table III).
|Table III Prevalence of premalignant lesions and CC by year and age group|
|CC = cervical cancer; LSIL = low squamous intraepithelial lesions; HSIL = high squamous intraepithelial lesions|
Cervical Cancer is a worldwide public health problem, since it is the neoplasm causing the second most deaths among women. Although the Programa Nacional de Detección Oportuna de Cáncer (PNDOC) has been implemented in Mexico since 1974, mortality from cervical cancer over the last 25 years has not decreased significantly. The main tool of the PNDOC for early detection of this type of cancer is cervical cytology. In this regard, in Mexico it has been reported that cervical cytology, rather than being a tool for early detection of cytological abnormalities, frequently detects cases of CC in advanced stages.19
An important fact highlighted by the analysis of information from the LARCE database is the percentage of limited and inadequate cytology samples (Table I); the sum of the two percentages reaches almost a quarter of the samples LARCE receives annually. Limited samples per se have a tendency to diagnostic error, which is attributed to sampling. This indicates the need to implement training programs for cytologic sampling.
It is estimated that the effective implementation of an early detection program for cervical cancer could prevent between 20 and 60% of deaths from this disease. In Mexico the current early detection program, based on cervical cytology, prevents less than 13% of potentially preventable cervical cancer deaths, which is due to low coverage and low quality standards.14,20 It is important to note that even with appropriate quality standards, conventional cytology has a relatively low sensitivity (53%),21 so the success of the test lies in its constant repetition and the systematic monitoring of patients with cytological abnormalities.22 The constant repetition of the test is related to the frequency with which the patient comes to have cytology performed. This is apparently not happening in the population captured by the LARCE, since a relatively similar percentage was seen of first-time patients (first time in life) compared with patients with previous cytology (1, 2, and 3 years or more). Our data suggest that the inclusion of women over 25 years in cytological screening is insufficient, so strategies should be devised to raise awareness in the female population and increase spontaneous admission to cytological screening programs. These results correlate with those reported by Donoso et al., who found a similar problem in the Chilean population.23 In addition, it is necessary to assess extending the age range under 25 for cytology in patients; LARCE receives for analysis samples from patients under 25, and the data indicate a high prevalence of low-grade lesions and the presence of high-grade lesions. Relatedly, a study by Valderrama et al. in a population of students in Lima, Peru, showed a high incidence of cervical lesions and HPV infection in the 21-23 age range.24 Similarly, Ulate-Arguedas and Alfaro-Pacheco found a prevalence of 3.69% for abnormal cytology in 2011 in a female population under age 20 in a region of Costa Rica.25 Therefore it is important to assess the inclusion of younger age groups in programs of early cervical cancer detection.
As for PL, it is noteworthy that LARCE data place Jalisco with a prevalence between 6 and 7.5% in the most critical age (35-45 years) (Figure 4). If we compare these data with those of world literature corresponding to exfoliative cytology, in which PL prevalence ranges between 5 and 30%, depending on the region and type of population studied,26,27 this indicates that the population of Jalisco, at least that captured by the LARCE, is in the lower range of prevalence, resembling populations in developed countries. This could be because the population captured by LARCE is the population insured by IMSS, placing these women at an average social status, with access to health services.
The data from LARCE indicate that mild dysplasias have an overall frequency of 5.3%, while moderate decrease to 0.18%, and severe to 0.05%, so a low frequency of in situ and invasive cancer is observed (0.03%). The prevalence of cervical lesions (5.52%) in the population captured by LARCE is relatively minor compared to that reported for other regions of Mexico and Latin America. The number of inadequate plus limited samples for cytological assessment is very high, indicating problems at the time of sampling and, above all, the need to implement training programs for sampling. Furthermore, a high proportion is observed of women going in for cytology for the first time in their lives in older age groups. This shows us that there is a population group that goes in for cytology late; it would therefore be advisable to delve into the causes of this behavior.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.