Razi Journal of Medical Sciences

Background & Aims: Cervical cancer is the second most common cancer among women worldwide. Annually more than half of all new cases occur in Asia, and about 80 percent of all cases are detected in developing countries (1-3). Viral infections are the cause of one-sixth of human cancers, including certain types of human papillomavirus, which play a major role in the development of almost all cervical cancers (4). Recent studies on the prevalence of HPV in Iran have shown that HPV16 along with genotypes 18, 31, and 53 are the most common genotypes in the female population. These studies have confirmed that the presence of high-risk and carcinogenic genotypes as well as multi-type infections are common among patients, which may be associated with an increased risk of cancer progression (5-10).
Since the effects of age and multiple HPV infections on the progression of lesions are more important than other risk factors in invasive cancers (11). The aim of this study was to determine the distribution of the human papillomavirus genotypes. The relationship between age and multiple HPV infections as well as the interaction of these two important parameters in the progression of lesion deterioration in women with abnormal cervical cytology result was investigated in order to understand the role of these factors in the incidence of invasive cervical cancer and providing effective and preventing actions.
Methods: In a period of six months, a total of 110 women with abnormal cytological and histological results of cervical liquid smear samples were collected. Cytopathologic characterization was categorized by the Bethesda 2014, a global system for Reporting Cervical/Vaginal Cytologic findings including atypical squamous cell of unknown significance (ASCUS), low‑grade squamous intraepithelial lesions (LSIL), high‑grade squamous intraepithelial lesion (HSIL), squamous cell carci­noma (SCC) and adenocarcinoma (ACA). In the present study, cytology results of ASCUS were considered abnormal. Genomic DNA from cervicovaginal liquid-based ThinPrep samples was extracted using the DNA Extraction Kit. The purity of the extracted DNA was evaluated by a NanoDrop spectrophotometer. The PCR assay for the β-globin gene was carried out as an internal control for each sample. Samples with positive results of β-globin were then amplified in PCR assay with general consensus GP5+/GP6+ primers, subsequently genotyping analysis of different HPV types was performed using INNO-LiPA HPV Genotyping Extra II Amp assay. The relationship between age and the multiplicity of HPV infections on the progression and deterioration of lesions were analyzed using statistical tests in SPSS 23.
Results: In the present cross-sectional study, all subjects had an infection with at least one human papillomavirus genotype. A total of 27 different genotypes were identified in the sample population, including 18 high-risk and 6 low-risk HPV genotypes.
Among all 110 samples, 74 patients (67.3%) had ASCUS cytology results, 24 patients had LSIL results (21.8%) and 12 Patients had HSIL results (10.9%). 52 out of 110 patients, had one type of HPV infection (47.3%) and 58 patients were co-infected with several different HPV genotypes (52.7%).
The mean age of all subjects was 36.2 years. The minimum age was 22 and the maximum age was 50 years. The mean age of women with ASCUS lesions was 35.9 years, 36.4 years in women with LSIL results, and 37.7 years in women with HSIL results.
A significant relationship observed between aging and the progression of the severity of the lesions. On the other hand, the present study did not show a significant relationship between multi-type HPV infections and increased severity, as well as the cooperative relation of age and multi-type HPV infections with increased severity of lesions.
Conclusion: Iran has a population of 25 million women over the age of 15 who are at risk for cervical cancer. The prevalence of cervical cancer in Iran is 6.64% and this cancer accounts for 34.2% of all cases of female cancer in Iran(12).
Nearly a decade interval between HPV infection and invasive cervical cancer incidence provides a golden opportunity for women to prevent the progression of precancerous lesions with early diagnosis and effective treatments(13). Significant relationship between age and increasing the severity of lesions, proves that lack of general awareness of cancer screening and timely detection among young women will lead to progression of invasive cancer, which could have been easily prevented.
According to the results of the present study, HPV infection has 100% prevalent among women with dysplastic lesions and all 18 high-risk HPV genotypes that could be identified by the relevant test were observed in the sample population. Multi-type HPV infections are common in cervical liquid samples of HPV-positive individuals, especially in women with severe intraepithelial lesions.
Rates of HPV infection and the incidence of cervical cancer in developing countries remain high, therefore, it is necessary to optimize HPV DNA-based diagnostic tests at lower costs so that they can be performed with routine Pap smear tests. With regular screening, HPV diagnostic testing, and considering the age factor and the type of HPV infection in terms of risk factors of carcinogenesis, it is possible to prevent the progression of cervical cancer by providing appropriate health services for all women (14).