Advanced Biomedical Research

: 2023  |  Volume : 12  |  Issue : 1  |  Page : 221-

Transitional Epidemiology of Human Papillomavirus Infection in Iran: A Cross-Sectional Study and National Review

Malihe Hasanzadeh1, Saeid Amel Jamehdar2, Leila Mousavi Seresht3, Mohammad Taghi Shakeri4, Somaye Bolandi1,  
1 Department of Gynecology and Oncology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
2 Department of Virology, Antimicrobial Resistance Research Center, Avicenna Research Institute, School of Medicine, Mashhad University of Medical Sciences; Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3 Department of Gynecology and Oncology, Isfahan University of Medical Sciences, Hezarjarib Street, Isfahan, Iran
4 Department of Biostatistics, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran

Correspondence Address:
Leila Mousavi Seresht
Department of Gynecology and Oncology, Isfahan University of Medical Sciences, Hezarjarib Street, Isfahan


Background: The high prevalence of cervical cancer in developing countries, despite its preventive nature, makes the disease a principal matter of concern for scientific studies. Providing global availability of primary and secondary preventive methods based on the high-risk human papillomavirus (HPV), which is the well-known pathogenesis in most malignant cervical lesions, has become the World Health Organization's (WHO's) critical target for 2030. Considering the demographic diversity and manufacturing of the internal vaccine in Iran, there is need for more study on the cost-effectiveness of these strategies. Materials and Methods: This study intends to assess female HPV prevalence at the time in Iran provinces, especially in the capital province, Khorasan Razavi, in the north to establish a scientific rationale for conducting further studies on arguments for and against national HPV prevention strategies in line with the WHO. In this population-based study, the HPV prevalence was evaluated in 900 cervical samples accumulated between 2012 and 2015. The data were later compared with recently published data in the same province, in the north of Iran. Result: Based on the results of our cross-sectional study, the estimated prevalence of HPV infection in the northern female population was 4.1% in 2015 and significantly increased to 35% in 2021. Conclusion: The hypothesis of the impact of behavioral and cultural changes in addition to population aging on general health indicates the need for national health promotion strategies. Additionally, it emphasizes the critical significance of conducting further investigational studies to obtain the actual and updated prevalence of HPV in Iran.

How to cite this article:
Hasanzadeh M, Jamehdar SA, Seresht LM, Shakeri MT, Bolandi S. Transitional Epidemiology of Human Papillomavirus Infection in Iran: A Cross-Sectional Study and National Review.Adv Biomed Res 2023;12:221-221

How to cite this URL:
Hasanzadeh M, Jamehdar SA, Seresht LM, Shakeri MT, Bolandi S. Transitional Epidemiology of Human Papillomavirus Infection in Iran: A Cross-Sectional Study and National Review. Adv Biomed Res [serial online] 2023 [cited 2023 Sep 28 ];12:221-221
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Full Text


Ever since the recognition of the human papillomavirus (HPV) as the direct cause of cervical pre-malignant and malignant lesions, it has become one of the most common gynecological neoplasms, mostly in developing countries, constituting approximately 88% of all cases.[1],[2] These double-stranded DNA (dsDNA) viruses are categorized into at least two classes, including the low-risk types that cause benign epithelial lesions, the high-risk or oncogenic genotypes (HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59), and the probably-high-risk HPV (HPV26, 53, 66, 67, 68, 70, 73 and 82) that are responsible for malignant transformation in infected host cells.[3] The World Health Organization (WHO) recently declared the need for global support in eliminating cervical malignancies up to 2030.[4] In this regard, primary prevention through prophylactic vaccination has higher priority than screening for cancer, as this timely measure reinforces societies against not only cervical lesions but also other HPV-related malignancies like oropharyngeal, anal, penile, vulvar, vaginal and, to some extent, breast cancer, all of which were considered as the etiology of approximately 5% of global cancer burden in 2018.[5] Even though most high-income countries have a national program of vaccination for adolescents, the cost-effectiveness of these strategies remain controversial in low- and middle-income countries (LMICs). The present study was conducted to evaluate the exact HPV burden in Iranian females by a cross-sectional and comparative study in order to accumulate required evidence to revise the national cervical cancer screening guidelines. The WHO recommended program aims to reduce the global cervical cancer prevalence to less than 4 cases per 100,000 women per year, reduce incidence by 97%, and prevent nearly 74 million cervical cancer–related deaths by the end of this century in LMICs. The content of this program consists of prophylactic-vaccination in more than 90% of girls of eligible age, accessibility of high-performance screening options for more than 70% of women of eligible age, and offering primary HPV testing and detection to patients in pre-malignant phase in 90% of new cases by the end of this decade,[6],[7] which is predicted to extricate nearly 300,000 women from premature death in ages of 30–69 years.[8] As the clock ticks by the second, now is the time for international commitment to accelerate the elimination of HPV-related cancers as a public health goal with the most cost-effective modalities.

 Material and Methods

Studied population

A population-based study between November 2012 and August 2015 among twenty urban and rural centers in, Khorasan Razavi, the northern province of Iran and with ethical board number IR.MUMS.REC.1388.101, was conducted. The included cities were selected using multi-stage cluster sampling and cervical cytology was performed on 900 healthy married Iranian women with no history of documented cervical pre-malignant or malignant lesions or HPV-vaccination aging from 15 to 70. The demographic data including the level of education, employment, lifetime number of male sexual partners, age during first sexual intercourse, history of sexually transmitted diseases, rural or urban residency, contraceptive methods, and smoking history (of more than two years) were recorded. In the second step, these findings were compared to a recent statistical analysis of HPV prevalence in the same province.

Sample preparation

Cervical specimens were collected with a cervical brush and suspended in a 5-ml preservation solution (Steril Buffer phosphate solution, PBS). The tubes were centrifuged at 2500 rpm for 10 minutes, the supernatant was removed and discarded, and the pellet obtained was stored at −80°C until DNA extraction.

DNA extraction

DNA from the sample was extracted with a RIBO-sorb nucleic acid extraction kit (AmpliSens, Russia) according to the manufacturer's protocol. Finally, the DNA was eluted with 100 μl of elution buffer, and extracts were stored at −20°C.

DNA amplification and detection

Amplification of HPV DNA was carried out with universal primers GP5: 5-TTTGTT ACTGTGGTAGATACTAC-3 as an upstream primer, and GP6: 5-GAAAAATAAACTGTAAATCATATTC-3 as a downstream primer. Beta macroglobulin gene was used as an internal control. The sequence of upstream and downstream primers were 3-GAAGAGCCAAGGACAGGTAC-5 and 3-GGAAAATAGACCAATAGGCAG-5, respectively.

HPV genotyping

All positive samples underwent HPV-specific polymerase chain reaction (PCR) using AmpliSens HPV 6/11 and a high-risk Eph PCR kit. The PCR protocol was carried out according to the manufacturer's protocol. Finally, detection of the amplified products was done using electrophoretic in agarose gel.

Statistical analysis

The normal distribution of data was analyzed using the Kolmogorov–Smirnov test. A comparison between the two groups was performed by independent t-test for quantitative data, and finally the Chi-squared test was used to compare qualitative parameters. All analyses were performed with IBM SPSS Statistics version 23 software. Differences were considered to be statistically significant when P values were <0.05.


The estimated HPV prevalence in this cross-sectional study among healthy women of Khorasan Razavi in 2012–2015 was 4.1% (37/900); more precisely, nearly 70.2% (26/37) had infection with high-risk genotypes, 19% (7/37) were infected by low-risk types, and 10.8% (4/37) of patients were positive for both [Figure 1].{Figure 1}

About 37.8% (14/37) of positive tests belonged to HPV16, which seems to be the most prevalent genotype followed by HPV18 (16.2%, 6/37), HPV45 (8.1%, 3/37), HPV31 (5.4%, 2/37), HPV33 (2.7%, 1/37), and no cases of HPV39, 51, 52, 56, 58, 59, and 68 were detected in this population. The calculated statistics of age-specified HPV prevalence was 6.4% in those aged 25–29 years, 5.9% in 20–24 years, 4.6% in 30–34 years, and 3.4% in women older than 45 years. In other words, the HR-genotypes were more common in younger women [Figure 2].{Figure 2}

There were no significant differences in contributing factors including age, marital status, education, age of menarche, delivery status, and the number of sexual partners except for oral contraceptive pills usage (P = 0.02) and smoking (P = 0.03). The use of oral contraceptive pills for an average of 6.1 years was found to be significantly correlated with HPV infection. The last finding was the significant difference in the prevalence of HPV between urban and rural centers, which was 6.1% (22/360) and 2.8% (15/540), respectively (P = 0.018).


The latest report of the WHO on cervical cancer screening infirmity in Iran,[9] our limited knowledge about the real HPV distribution in non-symptomatic patients in different parts of the country, and the introduction of a national bivalent HPV vaccine (papilloguard®, recombinant, type 16/18) persuaded us to conduct a comparative study between the non-published data on HPV prevalence in north Khorasan Razavi, the most northern province of Iran, in 2015 and the reported data in 2021. To the best of our knowledge, there has been no comparative study focusing on the transitional changes in HPV prevalence in specific province in Iran in order to investigating the cultural and behavioral changes. Based on the present study, the HPV prevalence in Khorasan Razavi province, as one of the extended regions in Iran, has had a considerable rise from 4.1% to 35% from 2015 to 2021.[10] The percentage of multiple-type infection has expanded from 3% to 11. 2%. This is a strong evidence supporting the hypothesis of transitional demographics in Iran,[11] what had also been suggested in Rezaee Azhar et al.[12] study in Tehran province with a growing rate of up to 55.7% and 52% infection in male and female. Another significant point is the difference between the most common subtype which has changed from type 16/18 to 51/16. This difference could be explained by the probability of contagious infections from outside of this province and the urgent need for political decisions on the educational programs about the importance of HPV and the route of its transmission. The other point in this comparison is the age of infection. Although the youngest ages—mostly 25 to 35 years old—constituted the greatest proportion of infected cases, there has been a marked increase in the prevalence of HPV infection between 15- and 25-year-old participants from near zero in 2015 to about 14.6% in 2021, based on an article published by Sabet et al.[10] This increase can be strongly related to the change in sexual behavior including great numbers of sexual partners in parallel with inattention to preventive measures and the reduction in the age of first sexual contact, which again emphasizes the need for educational programs on sexually transmitted infections and HPV transmission before high school, protective behaviors like improvement of genital hygiene, and actualizing the WHO cervical cancer elimination model that includes a global attempt for vaccination coverage of girls under 14 years old[8],[12] before their first sexual contact. Undoubtedly, both factors can be attributed to the Iranian population. The other hypothesis around the predicted growing rate of HPV infection in future is the rule of neighboring countries like Pakistan with high rate of HPV infection, which could have great cultural and population interaction with Iran.[13] Although the price of vaccination and lack of financial support from the WHO for implementation of vaccines have been considered as the main culprits in the limitation of vaccine coverage within different countries, there are other less recognized barriers to vaccination such as the lack of knowledge about transmission methods of HPV infection and negative attitude toward the vaccines' benefit and safety.[14] These obstacles accentuate the need for informative public interventions in priority planning in our country. Iran, an Asian country with more than 25.6 million women over 15 years of age and nearly 6.4 million cases susceptible to cervical cancer based on present incidence rates and other reports on the most prevalent age range of 20–40 years in Iran, requires expert analysis on the rationale behind vaccination of HPV infection in line with the WHO Cervical Cancer Elimination Modelling Consortium.[12],[15] It is needless to point out the long-term effects of vaccination on the incidence of cervical cancer; however, current vaccination requires a long time to reach the WHO elimination goal. Based on present national prevention program in Iran, adolescent vaccination cost more than benefit.[16] Present reports on HPV trends emphasis on the need for revising this approach in the country.

Although most of the infections are expected to be eliminated within two years, the carcinogenic potential of persistent high-risk HPV has been established in clinical studies. Therefore, the goal of HPV testing kits is to illuminate the subtypes with high potential in upregulation of viral oncoproteins E6 and E7 along with less than 50% chance of clearance in two years. In this regard, several types of HPV devices are introduced; however, what makes considerable limitation for comparative studies like the present study is lack of specific viral-load cut point with the likelihood of progression to dysplasia in different populations.[17] Another significant point in studying the prevalence is differentiating the prevalent genotypes of HPV according to the patients' history of vaccination, which is considered to be a pivotal factor and has been neglected in prior regional studies in many countries, including Iran.[18],[19] Differences in designing method, the number of studied cases, and the accumulated HPV prevalence based on age and specific provinces in prior reports in Iran has been illuminated in [Table 1] and [Figure 3].[10],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36]{Figure 3}{Table 1}

Regarding the present study, Safaei et al.[21] and Khodakarami et al.[37] reported a prevalence of 5.1% and 7.8% in 2010–2012 in a population-based study in Shiraz and Tehran, respectively. What seems to be of great significance is the limitation of the aforementioned study to referral patients despite non-symptomatic participants, which should be taken into account. The lack of HPV-based test availability due to its cost, with no insurance support, despite its established superiority in detecting precancerous lesions in randomized trials is another noteworthy complication in LMICs like Iran, which again rationally emphasizes on the lack of information about accurate HPV prevalence.[17]


In summary, particularly focusing on the role of HPV infection in cervical cancer development, especially in LMICs having a burden of more than 88% of all cases, there is an absolute need for promoting national prevention strategies in line with the WHO multicountry modelling strategy. It is clearly of great importance that almost 100% of cervical and most of the other mentioned neoplasms have been developed in consequence of persistent high-risk and probably-high-risk HPV infections.[38] Therefore, the aforementioned WHO recommendation on the cervical cancer elimination targeting program requires further investigational study on its cost-effectiveness in Iran, especially with the introduction of the nationally manufactured bivalent HPV vaccine.[7] It is of great importance to point that there is no additional gain in vaccinating boys if HPV coverage is as high as 90% among girls. However, this hypothesis is true when the goal is to prevent cervical cancer and not the other HPV-related malignancies in both genders. Another notable point is the negligible benefit of catch-up vaccination in older girls in reducing the overall prevalence of cervical cancer.[7]

Present comparative study emphasis on the fundamental need of HPV-infection incidence rate, risk factors of transmission and persistency, and prognosis in different areas to assess the cost-effectiveness of national primary and secondary preventive planning. Moreover, as there are no predictive models based only on screening for the reduction of cervical cancer in the WHO's global strategy on the elimination of cervical cancers,[7] it is highly recommended that further studies on the analysis of the cost-effectiveness of HPV vaccination be designed based on funding sources, HPV trends, HPV national vaccine (papilloguard®, recombinant), and sexual behavior in public health programs.


We want to thank Seyedeh Ghazal Shahrokh, MD, for her technical support as a language editor.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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