Histopathological Findings of Cervical Biopsy in Patients with Positive Human Papillomavirus (HPV)PCR
Siamak Naji1, Haleh Ayatollahi2, Rana Razavi3*, Samira Jahangard4 And Elham Rajabi5
1Department of Pathology, School of Medicine, Kosar Hospital, Urmia University of Medical Sciences, Iran
2Department of Obstetrics and Gynecology, School of Medicine, Solid Tumor Research Center, Research Institute on Cellular and Molecular Medicine, Kosar Hospital, Urmia University of Medical Sciences, Iran
3Department of Obstetrics and Gynecology, School of Medicine, IranMaternal and Childhood obesity research center, Kosar Hospital, Urmia University of Medical Sciences, Iran
4Department of Obstetrics and Gynecology, School of Medicine, Solid Tumor Research Center, Research Institute on Cellular and Molecular Medicine, Kosar Hospital, Urmia University of Medical Sciences, Iran
5Department of Obstetrics and Gynecology, School of Medicine, Iran Maternal and Childhood obesity research center, Kosar Hospital, Urmia University of Medical Sciences, Iran
Submission: August 29, 2022; Published: October 10, 2022
*Corresponding author: Rana Razavi, Department of Obstetrics and Gynecology, School of Medicine, Iran Maternal and Childhood obesity research center, Kosar Hospital, Urmia University of Medical Sciences, Iran
How to cite this article: Siamak N, Haleh A, Rana R, Samira J, Elham R. Histopathological Findings of Cervical Biopsy in Patients with Positive Human Papillomavirus (HPV)PCR. J Gynecol Women’s Health 2022: 24(1): 556128. DOI: 10.19080/JGWH.2022.24.556128
Abstract
Background: The human papillomavirus is currently one of the most important risk factors of cervical cancer, which is one of the three most frequent malignancies in women globally. As a result, this study aims to examine the histopathology of cervical biopsies in individuals who had a positive HPV PCR titer.
Methods: The human papillomavirus is currently one of the most important risk factors of cervical cancer, which is one of the three most frequent malignancies in women globally. As a result, this study aims to examine the histopathology of cervical biopsies in individuals who had a positive HPV PCR titer.
Results: The results of our study showed that with increasing the marriage age and duration the infection with high-risk types of HPV was higher in the subjects. Furthermore, ASCU was reported in 21 (35.6%) patients, LSIL lesions in 7 (11.9%) cases, and HSIL lesions in 2 cases (3.4%).
Conclusion: Our findings demonstrated the diversity of multiple HPV species in the examined samples, as well as their relationship to the factors evaluated. hence, there is a strong need to investigate the incidence of Pap smear pathologies in a larger statistical sample in order to provide a more realistic and critical picture of the virus epidemiology in Iranian society. In future studies, it is also crucial to evaluate other characteristics such as couples’ sexuality and education degree.
Keywords: Human Papillomavirus; PCR; Pap smear; Cervix cancer
Introduction
Papillomaviruses (PVs) are a small group of viruses that have double-stranded DNA and are members of the papillomavirus family [1,2]. human papillomavirus (HPV) is the most common sexually transmitted illness , that infects over 80% of women over the age of 50 in the United States [3]. More than 85 strains of HPV have been discovered so far, with at least 35 of them being detected in female genital infections [4]. Cohort studies have revealed that HPV DNA is required for cervical neoplasms growth, and its elimination predicts neoplastic cell regression [5-7]. Women who have HPV DNA but no cervical legions are at a higher risk of Squamous Intraepithelial Lesion (SIL) progression [8].
Based on the relative risk of developing high-grade legions and invasive malignancies, HPV viruses are classed as high-risk (HPVs 16, 18, 45, 56), medium-risk (HPVs31,33,35,51,52,58), and low-risk (HPVs 6,11,42,43,44) [9-11]. Cervical cancer has been linked directly to HPV, with a portion of the viral genome (E proteins) causing malignant cell transformation, chromosomal changes in cervical epithelial cells, and the development of cervical cancer [12].
Following the development of a primer for HPV detection by polymerase chain reaction (PCR), it was shown that HPV plays a significant role in cervical cancer, since virtually all the samples contained HPV DNA [13, 14]. However, since the majority of precancerous lesions arise in the squamous epithelium or metaplastic endocervical epithelium, the identification of HPV DNA in Low grade squamous inthraepithelial lesion (LSIL) and High grade squamous inthraepithelial lesion (HSIL) lesions inside the squamous epithelium has grown to 80-90 % with the advancement of HPV detection technologies [13,15].
Overall, the community and at-risk populations need early and prompt identification and treatment of human papilloma infections using cost-effective and accurate technologies such as PCR. Therefore, the purpose of this study is to look at the histopathology of cervical biopsies from patients with positive HPV PCR titer. In which we were able to take a step toward a more accurate understanding of this illness in the Iranian community.
Methods
Study Overview
In this cross-sectional study, the histopathological changes of cervical biopsies were investigated in 59 patients that were referred to Shahid Motahari Hospital’s cancer clinic between 2016 and 2017 who had a history of HPV infection verified by PCR and underwent biopsy. Data were collected using a researcherdesigned checklist that includes CNI 1, 2, and 3, as well as age, marital status, and contraceptive method usage. In this study, we assessed patients with HPV history that was confirmed by PCR and excluded the patients’ records that lack of information due to any reason and we were unable to update the record after a phone call. In this study, we classified the patients based on the type of HPV that they were infected with . As a result, patients who tested positive for HPV 16, 18, 45, and 56 were assigned to group I (the high-risk group), while patients who tested positive for HPV in the moderate and low-risk groups were assigned to the other group (the group II).
Statistical Analysis
In this study, the t-test or its non-parametric equivalent was used to compare quantitative data, while qualitative data was compared using the Chi-square test and, if appropriate, the Fisher test. In all instances, the significance level was less than 0.05.
Results
Basic Information
According to our study’s findings , the mean and standard participants’ age deviation was 38.30 8.78 years, with a range of 21-52 years. This study’s participants were all married. In our study , ten patients (16.94%) were remarried. In our study, the mean and standard deviation of marital length was 15.16 7.33 years with a range of 6-29 years. In our study, 36 cases (61%) used combined oral contraceptive pills and 14 cases (23.7%) used intermittent method, 8 cases (13.6%) used condoms and one case used ampules for contraception. In our study, 23 cases (39%) were in the high-risk group for HPV (group I), and 36 patients (61%) were in the lower-risk groups for HPV (group II).
Histopathological Findings
In our study , 9 individuals had CIN1, 2 had CIN2, 2 had CIN3, and the others were normal. There was a significant relationship between patient pathology and HPV type (groups I & II) (p = 0.002). So that, CIN was found in 11 out of 33 people in Group I, while only two out of 36 people in Group II had CIN1. Similarly, a significant difference was observed between the mean age and the two classified HPV groups (45.47. 5.83 vs. 33.72 ± 7.14, p = 0.001), which showed that the mean age was higher in group I. The mean marriage duration was significantly different in both groups therefore it was about 6 years longer in group I (18.56 ± 7.12 vs. 13.02. 6.70, p = 0.04). There was no significant difference (p = 0.629) between the contraceptive methods used by patients and the two HPV groups. Furthermore, the findings of our study revealed that the rate of ASCUS in the patients analyzed was 21 cases (35.6%), which had a significant association (P = 0.001) with the study’s groups. Furthermore, 9 cases of LSIL lesions were detected in our samples, with 7 cases in the high-risk group and 2 cases in the low-risk group, which were statistically significant (P = 0.027) with each other. HSIL lesions were seen in two individuals (3.4%) in our cases, one in the high-risk group and one in the lowrisk group.
Discussion
The epidemiology of HPV positive cases in our study was effectively described by taking into account the histological status and pathology of the examined patients at Shahid Motahari Hospital in Urmia. In this respect, in our study HPV positive patients were divided into high-risk and low-risk groups, in which had a significant relationship with the type of pathology the patient infected with, the patient’s histology (squamous lesions and LSIT), and the patient’s age. These findings may point to a greater emphasis on high-risk disease categories and, as a consequence, improve illness management.
In literature, the average age of cervical cancer onset is 50-52 years [16,17],which is older than the average age of our study’s patients (38 years). The target population might be responsible for the older average age of patients in this evidence. Therefore our study’s patient were infected with human papillomavirus rather than cervical cancer, hence, in fact they were a population at risk for cervical cancer. Several researchers have examined the patients’ marital status and the number of their sexual partners [18,19]. In all investigations, having several sexual partners was shown as a risk factor for cervical cancer [20,21]. According to our findings, the average length of marriage duration in the patients with higher-risk papilloma is much longer than in patients with high-risk papilloma virus. In addition, it’s necessary to mention that almost 17% of the patients in our study were remarried. In a study done by Monroe et al. [22], women who had used OCP for less than 5 years were not at higher risk cervical cancer group, but this risk was observed after taking these pills for more than 5 years. Moreover, in another evidence, taking the OCP for more than 6 years was listed as a cancer risk factor [20]. Therefore, approximately 61 percent of the individuals in our study utilized OCP. However, no statistically significant link was found between the usage of contraceptive methods and the low-risk and high-risk HPV groupings. Having unprotected intercourse with an HPVinfected individual, has been demonstrated in earlier researches [23,24] to be a main risk factor for cervical cancer. According to Nojomi et al. [16], around 75% of patients with cervical cancer had never used a condom. As a result, the absence of a meaningful association in our study can be attributed to the study’s small sample size. It is essential that in future studies , a larger statistical population will be chosen, and the patients’ spouses’ sexual function would be assessed.
In our investigation, ASCU was reported in 21 (35.6%) patients, LSIL lesions in 7 (11.9%) cases, and HSIL lesions in 2 cases (3.4%). In this respect, the frequency of ASCUS, LSIL, and HSIL in a study done by Condyle et al. [25] with the same purpose was comparable to our study, while the rate of AGUS in this study was reported to be 7.3 %, which was not reported in our study , it can be due to the insufficiency of the Pap smear method in this study, as well as the lower incidence of AGUS in our study region, which deserves more examination.
Conclusion
Overall, the findings of our study suggest that it is necessary to pay more attention to the high-risk types of the disease and, as a consequence, improve the disease management. More researches in various sections of the population seems to be critically important in this respect. More specific information may be acquired to describe the differences between groups more clearly.
Acknowledgement
The authors gratefully acknowledge the financial support for this work that was provided by Research and Technology Committee of Urmia University of Medical Sciences. We thank the honorable all of the personnel who work in the Research & Development, Kosar Hospital, Pathology Department of the hospital.
Funding
Research and Technology Committee of Urmia University of Medical Sciences.
References
- De Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H (2004) Classification of papillomaviruses. Virology 324(1): 17-27.
- Bravo IG, Félez-Sánchez M (2015) Papillomaviruses: Viral evolution, cancer and evolutionary medicine. Evol Med Public Health 2015(1): 32-51.
- Braaten KP, Laufer MR (2008) Human Papillomavirus (HPV), HPV-Related Disease, and the HPV Vaccine. Rev Obstet Gynecol 1(1): 2-10.
- De Villiers EM (1994) Human pathogenic papillomavirus types: an update. Curr Top Microbiol Immunol 186: 1-12.
- Muñoz N, Bosch FX (1992) HPV and cervical neoplasia: review of case-control and cohort studies. IARC Sci Publ 119: 251-261.
- Coker AL, Gerasimova T, King MR, Jackson KL, Pirisi L, et al. (2001) High-risk HPVs and risk of cervical neoplasia: a nested case-control study. Exp Mol Pathol 70(2): 90-95.
- Kreimer AR, Brennan P, Lang Kuhs KA, Waterboer T, Clifford G, et al. (2015) Human Papillomavirus Antibodies and Future Risk of Anogenital Cancer: A Nested Case-Control Study in the European Prospective Investigation into Cancer and Nutrition Study. Journal of Clinical Oncology 33(8): 877-884.
- Lau S, Franco EL (2005) Management of low-grade cervical lesions in young women. CMAJ 173(7): 771-774.
- Lorincz AT, Reid R, Jenson AB, Greenberg MD, Lancaster W, et al. (1992) Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types. Obstet Gynecol 79(3): 328-337.
- Muñoz N, Bosch FX, de Sanjosé S, Herrero R, Castellsagué X, et al. (2003) Epidemiologic Classification of Human Papillomavirus Types Associated with Cervical Cancer. N Engl J Med 348(6): 518-527.
- Moeinzadeh M, Kheirkhah B, Amini K, Pouryasin A (2020) Classification and identification of human papillomavirus based on its prevalence and development of cervical lesion among Iranian women. Bioimpacts 10(4): 235-242.
- Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, et al. (2004) Mechanisms of human papillomavirus-induced oncogenesis. J Virol 78(21): 11451-11460.
- Burd EM (2003) Human papillomavirus and cervical cancer. Clin Microbiol Rev 16(1): 1-17.
- Tao X, Zheng B, Yin F, Zeng Z, Li Z, et al. (2017) Polymerase Chain Reaction Human Papillomavirus (HPV) Detection and HPV Genotyping in Invasive Cervical Cancers with Prior Negative HC2 Test Results. American Journal of Clinical Pathology 147(5): 477-483.
- Bao L, Si Q, Jia L, Ren X, Ma R, et al. (2015) Detection of human papillomavirus and expression of osteopontin in cervical cancer specimens. Mol Med Rep 11(1): 447-453.
- Nojomi M, Modares Gilani M, Erfani A, Mozafari N, et al. (2007) The Study of Frequency of Risk Factors of Cervical Cancer Among Women Attending General Hospitals in Tehran, 2005-2006. RJMS 14(56): 189-195.
- Benard VB, Watson M, Castle PE, Saraiya M (2012) Cervical carcinoma rates among young females in the United States. Obstetrics and gynecology 120(5): 1117-11123.
- Conserve DF, King G, Dévieux JG, Jean-Gilles M, Malow R, et al. (2014) Determinants of HIV serostatus disclosure to sexual partner among HIV-positive alcohol users in Haiti. AIDS Behav 18(6): 1037-1045.
- Ashenhurst JR, Wilhite ER, Harden KP, Fromme K (2017) Number of Sexual Partners and Relationship Status Are Associated With Unprotected Sex Across Emerging Adulthood. Arch Sex Behav 46(2): 419-432.
- Liu ZC, Liu WD, Liu YH, Ye XH, Chen SD, et al. (2015) Multiple Sexual Partners as a Potential Independent Risk Factor for Cervical Cancer: a Meta-analysis of Epidemiological Studies. Asian Pac J Cancer Prev 16(9): 3893-900.
- Siokos AG, Siokou-Siova O, Tzafetas I (2019) Correlation between cervical carcinogenesis and tobacco use by sexual partners. Hell J Nucl Med 22(Suppl 2):184-90.
- Moreno V, Bosch FX, Muñoz N, Meijer CJLM, Shah KV, et al. (2002) Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study. The Lancet 359(9312): 1085-1092.
- Panatto D, Amicizia D, Trucchi C, Casabona F, Lai PL, et al. (2012) Sexual behaviour and risk factors for the acquisition of human papillomavirus infections in young people in Italy: suggestions for future vaccination policies. BMC Public Health 12: 623.
- Kombe KAJ, Li B, Zahid A, Mengist HM, Bounda G-A, et al. (2021) Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation. Front Public Health 8: 552028.
- Au WW, Sierra-Torres CH, Tyring SK (2003) Acquired and genetic susceptibility to cervical cancer. Mutat Res 544(2-3): 361-364.