Cervical cancer (CC) is among the cancers caused by HPV infection and the fourth for both incidence and mortality among women (Davies-Oliveira et al., 2021). In 2020, it accounted for an estimated 604,000 new cases and 342,000 deaths (Sung et al., 2021). It was the most commonly diagnosed cancer in 23 countries and was the leading cause of cancer death in 36 countries of which the vast majority of these countries are found in sub-Saharan Africa (Pizzato et al., 2022) including Ethiopia.

The prevalence of hr HPV infection in sub-Saharan African countries is unevenly distributed, ranging from 10.7% (Domfeh et al., 2008) to 97.2% (Sahasrabuddhe et al., 2007). The pooled prevalence of hr HPV in sub-Saharan African countries is 32.3%. Similarly, the genotype distribution of hr HPV varied based on geographical location. For example, in China, HPV-52, -16, -58, -18, and -53 determined as the most prevalent genotypes (Zhang et al., 2020). However, this distribution has a different pattern among African countries. HPV-16, -18, -45, -35, and -33 were the most prevalently identified genotypes among sub-Saharan African countries (Ogembo et al., 2015) while HPV-16, -52, -18, -39, and -31 are the widely distributed in the eastern part of Africa (Seyoum et al., 2022). In Ethiopia, the distribution of hr HPV specifically HPV-16, -52, -18, -58, and -45 is almost similar to the other East African countries (Derbie et al., 2019).

Infection with human papillomavirus (HPV) is the primary cause of cervical cancer (Xing et al., 2021). Around 229 different HPV types have been listed by the International HPV Reference Centre¹, and this number continues to expand. Among them, about 40 types of HPV can infect the genitals of men and women: the skin of the genitals, the vulva (the area outside the vagina), the anus and the lining of the vagina, the cervix, and the anus. These types can also infect the lining of the mouth and throat (Sendagorta-Cudós et al., 2019).

Genital/mucosal types are of the alpha-PV genus and are classified into oncogenic (high-risk) or non-oncogenic (low-risk) types based on their involvement in malignant lesions. Genotyping of the virus defines by the genetic sequence of the protective outer shell or capsid made of a protein called the Late gene 1 (L1; Soheili et al., 2021). Accordingly, the 15 high-risk (hr) HPVs (HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, -73, and -82) cause dysplasia and cancer. The other 12 are low-risk types (HPV-6, -11, -40, -42, -43, -44, -54, -61, -70, -72, -81, and CP6108), which usually cause low-grade mild dysplasia, genital warts, and respiratory papillomatosis. The remaining three are probable high-risk types (HPV-26, -53, and -66; Asiaf et al., 2014; Doorbar et al., 2015).

Currently, three licensed HPV vaccines constructed using L1 capsid antigens: 9-valent HPV vaccine (Gardasil 9, 9vHPV), quadrivalent HPV vaccine (Gardasil, 4vHPV), and bivalent HPV vaccine (Cervarix, 2vHPV) are available (Gillison et al., 2008; Roden and Stern, 2018). Hence, urgent and bold action is needed to scale up and sustain implementation of the evidence-based interventions to reduce cervical cancer as a public health problem, but such action must be strategic. Since the limited cross-protection offered by the current vaccines, generating scientific data regarding the hr HPV prevalence, genotype distribution, cytological profile and associated factors among the different populations is essential in predicting the efficacy of the current vaccine and devising new vaccine strategy (Senapati et al., 2017). In eastern Ethiopia, there is no data about the prevalence and genotype distribution of the virus. Therefore, this study was conducted to fill this information gap. Therefore, we determined the prevalence of hr HPV infection and cytological profile among sexually active women in Ethiopia.

This study is the first hospital-based study conducted at the molecular level to determine the molecular epidemiology of hr HPV infection among sexually active women in eastern Ethiopia. The presence of high prevalence and genotype heterogeneity of hr HPV as a cause of multiple HPV infections indicates a major public health problem that requires greater attention. Additionally, it showed that the detection rate of the virus has a direct correlation with abnormal cytology.

The overall prevalence of hr HPV infection was determined to be 13.1% which is low compared to previous studies in various African countries as high as 95% for example in Benin (Tounkara et al., 2020), 83.2% in Ethiopia (Wolday et al., 2018), 76.3% in South Africa (Ebrahim et al., 2016), 57.7% in Kenya (Menon et al., 2016), 53% in Zimbabwe (Marembo et al., 2019), 48.7% in Mozambique (Omar et al., 2017), 46.2% in Swaziland (Ginindza et al., 2017), and 41.5% in Burkina Faso (Ogembo et al., 2015) and genotype heterogeneity with 14 genotypes of hr HPV were identified. The low prevalence in the current study might be explained by the differences in the occupational and health status of the study participants. The current study was conducted on women with a different type of occupations and gynecological problems (from asymptomatic to invasive stage) with normal or abnormal cytological status. This proportional inclusion of women allowed might help us to identify the high level of genotype heterogeneity of hr HPV among women. However, various studies we used for comparison were conducted on female sex workers and people living with HIV (PLWHIV). As a result, the prevalence of HPV infection was 2–3 times higher among these segments of the population.

In contrast, the hr HPV infection in this study was higher compared to the research findings of 9.4% in Iran (Malary et al., 2016) and 12% in the Gambia (Camara et al., 2018), with comparable results of 13.1 and 13.7% were found in Tunisia (Ardhaoui et al., 2016) and Ethiopia (Ali et al., 2019). This comparable result may be due to the fact that the women included in the studies we used for comparison were sexually active women, which is similar to the participants in this study. Therefore, it is important to consider the demographic and health-related aspects of a population segment in order to make appropriate comparisons and take targeted interventions.

The prevalence of hr HPV infection among women with normal cytology was 11.9% and it was very close to the global average of 11.7% (Scott-Wittenborn and Fakhry, 2021) and 12.8% in Northern Africa, but it was low compared to the average of 57.3% in the southern, 42.2% in eastern, and 27.8% in western Africa regions (Ogembo et al., 2015). In the current study, HPV-16, -31, -52, -39, and -45 were the top five HPV types infecting women with normal cytology. This distribution was inconsistent with the global; HPV-16, -52, -31, and -53 (Bruni et al., 2019) and eastern African countries; HPV-16, -52, -18, -51, and -58 (Ogembo et al., 2015). Contrary to normal cytology, the highest prevalence of hr HPV infection (88.1%) was determined in women with abnormal cytology. The result of the current study is inconsistent with study findings conducted in the Middle East and North Africa (MENA) where the pooled prevalence was 54% (Obeid et al., 2020). Furthermore, in the current study, HPV-16 and -31 genotypes were found to be the main cause of lesions in women with abnormal cytology. This was inconsistent with the results of a meta-analysis in East African countries where HPV-16 and -52 were the main causes of lesions with ASCUS, LSIL, and HSIL cytological results. Whereas HPV-16 and -18 were the predominant HPV genotypes found in women with ICC. Among the possible reasons for this inconsistency could be related to bio-behavioral characteristics including cultural differences in age at first intercourse, lifetime number of sexual partners, and current smoking status (Lin et al., 2015). The distribution of HPV genotypes is spatially inconsistent across continents, countries, and even within a single country. This lack of uniform distribution makes the identification of HPV genotypes in every locality critical to implement vaccine-based disease preventive measures. In agreement with this conclusion, this study has a significant role in informing the HPV genotypes among women in eastern Ethiopia.

The current study also found that the hr HPV infection rate decreases as the age of the study participants’ increase. The highest prevalence of hr HPV infection (29.09%) was observed in women between 30 and 35 years of age, while the prevalence of infection was comparatively lower in women over 40 years of age. The age-specific prevalence of the disease in the current study is consistent with the results of previous studies (Smith et al., 2008; Bekos et al., 2018). This is likely due to the interaction between the natural history of the disease and the genotypes that cause the lesion. Molecular studies on HPV have suggested that patient age and HPV genotypes are independent factors influencing the regression and progression rates of cervical lesions (Ho et al., 1998; Bosch and Harper, 2006). Studies show that young women generally have higher spontaneous recovery (Cox et al., 2003; Moscicki et al., 2010).

Along with women’s age, the other strongest factor influencing the natural history of the disease is the presence of hr HPV (particularly HPV-16 and -18 genotypes) infection (Moscicki et al., 1998). These two genotypes increase the risk of persistent infection. In addition to these two main factors, smoking (Appleby et al., 2006), multiparity, and long-term use of oral contraceptives can double or triple the risk for progression to high-grade lesions or cervical cancer in HPV-infected women (International Collaboration of Epidemiological Studies of Cervical Cancer, 2006). If this study had been conducted using a longitudinal study design, it would have been possible to determine the viral persistence/ progression rate and assess the impact of hr HPV. However, we were forced to use a cross-sectional study design because of insufficient financial resources to conduct a longitudinal study design. This can be considered a limitation of this study.

The hr HPV infection continues to be a major public health problem among women of 30–35 years old. Although the prevalence was high in younger women, the age-specific HPV infection prevalence declines as the age increase. The presence of hr HPV irrespective of genotypes is highly correlated with cervical cell abnormalities. Genotype heterogeneity is observed suggesting the importance of periodic geospatial genotyping surveillance for vaccine effectiveness.

The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Institutional Health Research Ethics Review Committee (IHRERC) of the College of Health and Medical Sciences, Haramaya University, Ethiopia and the Armauer Hansen Research Institute Ethics Committee. The patients/participants provided their written informed consent to participate in this study.

AS, AdM, AnM, BS, RH, and AbA participated in proposal development, data collection, laboratory works, data analysis, and manuscript writing. TG conducted clinical examination, sample collection, and supervision of midwives during sample collection. AdA and AB participated in the cytological examination. DA participated in nucleic acid extraction, laboratory protocol review, HPV detection, and HPV genotyping. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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