Cervical cancer, the world’s fourth most common cancer, is becoming a concerning public health problem and accounts for 40.1% of new global cases of cancer in eastern Asia (Sung et al., 2021). China, the largest developing country, reported 109,741 new cases of cervical cancer and 59,060 cervical cancer-related deaths in 2020 (Cao et al., 2021).

Human papillomavirus (HPV) is a small, nonenveloped double-stranded DNA virus. More than 200 genotypes have been identified, of which approximately 40 genotypes infect the genital tract (Bzhalava et al., 2015; Luo et al., 2020). Most HPV infections are transient and can be eradicated by the immune system. Persistent infection induces cervical lesions. Based on pathogenicity, HPVs are divided into a low-risk category, which includes HPVs that can lead to cervical low-grade squamous intraepithelial lesions (LSILs), and a high-risk category, which includes HPVs that are strong carcinogenic factors that can induce cervical high-grade squamous intraepithelial lesions (HSIL) and invasive squamous cell carcinoma (SCC). More than 90% of HSIL and SCCs are HPV-associated. Therefore, HPV vaccination has been provided to prevent cervical lesions.

Accordingly, the 2-valent vaccine against HPV16/18 and 4-valent vaccine against HPV6/11/16/18 provide 70% protection against cervical cancer. The protection rate increases to 90% in persons who receive the 9-valent vaccine targeting HPV6/11/16/18/31/33/45/52/58 (Yan et al., 2021). However, vaccine appointments are not easy, especially for the 9-valent vaccine, and there are strict age limitations in China. It is worth noting that HPV vaccines play a prophylactic but not therapeutic role in cervical epithelial lesions and that their adverse effects should not be ignored (Morimoto et al., 2015). Additionally, the geographical distributions of HPV genotypes vary from region to region. Although HPV16 is generally considered highly carcinogenic and the most prevalent genotype responsible for more than 50% of cervical cancers in most regions of the world (Bletsa et al., 2021), some eastern Asian countries, such as Korea, Japan and China, have demonstrated higher prevalence rates of HPV58 and HPV52 in women (Asato et al., 2004; Nah et al., 2017; Zhang et al., 2018).

Therefore, investigating and understanding the prevalence of HPV genotypes and their related cervical lesions in a specific region is of great importance for formulating public health strategies and guiding the application of the HPV vaccine. The first study on the prevalence of HPV in the Hengyang district demonstrated that the infection rate between April 2010 and March 2012 was 22.6% (Li et al., 2013). During 2012–2018, the overall positive rate was 18.71% (Luo et al., 2021). However, the correlation between HPV prevalence and cervical morphology in Hunan Province had not been intensively studied. The gynaecology department of the First Affiliated Hospital of University of South China, the largest medical institution in southern Hunan Province, performs HPV genotype detection in approximately 20,000 people per year. This retrospective investigation reviewed HPV detection results, the prevalence of genotypes and the characteristics of HPV-associated morphologic abnormalities to provide useful references for the detection, prevention and control of related cervical lesions in southern Hunan Province.

Action toward achieving the global elimination of cervical cancer has been proposed by the World Health Organization (WHO) since 2018 (Kumar et al., 2019). Free screening for cervical cancer and breast cancer has been offered to rural women in China since 2009. At the beginning of 2022, urban women were also enrolled in the programme. As a sensitive method, HPV testing is usually used in combination with cytology for screening for cervical lesions (Hamers et al., 2022).

The fact that the HPV prevalence varies considerably on the basis of geography and population has prompted many investigations into regional epidemical strategies. Disparities also exist within countries.

The overall HPV infection rate in our study was 14.59%, which was lower than those in Guizhou (16.95), Sichuan (23.84%), Fujian (20.57%), Guangdong (19.81%), Shanghai (17.92%), Shandong (28.4%), Liaoning (16.1%), Henan (19.7%), and Jiangsu (26.92%) but higher than those in Xinjiang (14.02%) and Yunnan (12.9%; Li et al., 2016, 2020; Sun et al., 2017; Zhao et al., 2018; Chen et al., 2019; Jiang et al., 2019; Wang et al., 2019, 2022; Zhang et al., 2019, 2020; Luo et al., 2020). Compared to previous study, the HPV positive rate decreased significantly, which may be due to increasing health awareness led to increase participation in cervical screen (Luo et al., 2021). The distribution of the age-specific HPV infection rate presented a bimodal pattern, which was in accordance with the results of the majority of previous studies. The <20 years age group had the highest infection rate, possibly because new sexual behaviour increases the risk of virus exposure and an undeveloped immune system has an insufficient capability for virus clearance (Bergqvist et al., 2021; Yan et al., 2021). The 60–69 years age group had the second highest HPV infection rate. The reason could be a decreased ability to clear recent infection due to age-related immune senescence and persistent infections in older women from earlier exposures (Kang et al., 2014). Notably, the numbers of participants aged <20 and ≥60 were significantly less than those in the other groups. In fact, only a small minority of women under the age of 20 reported sexual behaviour. Fewer elderly women aged 60 years or older received HPV testing in the clinic, possibly because of reluctance due to an insufficient understanding or a lack of symptoms (He and He, 2020). Consistent with previous study (Yang et al., 2022), the current study shows that women with college education or from urban areas had lower risk of HPV infection. Higher education and convenient urban medical service may improve the health attention and practice of the population.

Single-type HPV infection and high-risk HPV infection in our study were the most common types of infections. The most common genotype worldwide is HPV16 (Crow, 2012), similar to that in northernmost China (Jiang et al., 2019; Zhang et al., 2020; Wang et al., 2022). However, the most prevalent genotype in southernmost China is HPV52 (Li et al., 2016, 2020; Chen et al., 2019; Zhang et al., 2019; Luo et al., 2020). In the south of Hunan province, the most common genotype has been changed from HPV 16 to HPV 52 (Li et al., 2013; Luo et al., 2021). Regardless of whether HPV16 or 52 ranks first, the top three genotypes in China are HPV16, 52 and 58 (Li et al., 2016, 2020; Sun et al., 2017; Zhang et al., 2018, 2019, 2020; Chen et al., 2019; Jiang et al., 2019; Wang et al., 2019, 2022; Luo et al., 2020). As the second most carcinogenic genotype in the world, HPV18 ranks only fourth in some Chinese areas or is not even in the top five in other provinces (Li et al., 2016; Zhang et al., 2018). Moreover, HPV53 is the fourth or fifth most prevalent genotype in most areas of China (Sun et al., 2017; Chen et al., 2019, 2021; Jiang et al., 2019; Wang et al., 2019, 2022; Zhang et al., 2019, 2020; Li et al., 2020; Luo et al., 2020), and is the most prevalent genotype among healthy women in other Asian countries (Ouh et al., 2018). Our study also demonstrated that HPV81 was the most common low-risk type, with the same overwhelming advantage in other Chinese provinces (Zhao et al., 2018; Chen et al., 2019; Zhang et al., 2019; Luo et al., 2020; Yan et al., 2021).

The multiple-infection rate in HPV-positive patients in the different age groups also showed a bimodal distribution. The peak occurred in the <20 years group, and the second highest rate was observed in the 60–69 years group, similar to the distribution of the age-specific HPV infection rate and likely explained by the same reasons (Li et al., 2020). Patients with multiple HPV infections had a longer duration of HPV infection and an increased risk of cervical lesions compared to patients with a single HPV infection (Kim et al., 2021). High-risk HPVs were also the predominant genotypes in coinfections. Among the top 10 dual infections, HPV82 was the only low-risk genotype. However, the oncogenic potential of each HPV genotype under coinfection conditions could not be assessed accurately because interactions and competition between the genotypes were unclear (Bernard et al., 2013).

Cytology screening in patients with a high-risk HPV genotype is the conventional method (Rebolj et al., 2022). The distribution of different cervical cytology results in each HPV genotype group, especially the high-risk genotypes, is helpful in evaluation of the risk of morphological changes. Our investigation showed that HPV16, 52 and 58 accounted for the top three genotypes resulting in cervical cytopathologic abnormalities, which was in accordance with data from other studies (Luo et al., 2020; Yan et al., 2021). Compared to the other genotypes, HPV16 was the major species in the ASC-H, HSIL and SCC cytology samples. Similar to other observations, HPV52 was the dominant genotype in cases with negative cytology and ASC-US (Li et al., 2020; Yan et al., 2021). Some HSIL were related to uncommon genotypes, such as HPV31 and HPV33. Approximately 16.67% of 126 patients with HPV33 had HSIL. In contrast, HSIL occurred in only 18 (approximately 9.52%) HPV18-positive cases. Colposcopy is recommended for women with HPV16/18, even if NILM is absent according to the American Society for Colposcopy and Cervical Pathology (ASCCP; Perkins et al., 2021). Based on our study, it is also appropriate to perform colposcopy screening in women with HPV52/58/31/33 in China.

The distribution of different pathological results for each genotype was similar to the distribution of cytopathological results. HPV16, 58, and 52 were also the major genotypes in women with histological abnormalities. Relative risk analysis demonstrated that women infected with HPV16, 31, 33, and 58 had an increased risk of HSIL compared with the other genotypes, which supports the above recommendation for additional colposcopy examinations in the population in China (Long et al., 2018; Yan et al., 2021). In our study, HPV16 and 18 were also the top two oncogenic genotypes associated with cervical cancer, consistent with the results of a previous study (Yan et al., 2021).

According to the guidelines from the American Cancer Society, HPV testing in combination with cytology or cytology alone should be phased out once full access to primary HPV examination for cervical cancer screening is available without barriers (Fontham et al., 2020). Therefore, HPV testing and prevention will play a more important role in epidemiological management in different regions. HPV16/18 were detected in 75.89% of cervical cancer samples in our study, suggesting that approximately 70% of cervical carcinomas could be prevented by bivalent or quadrivalent HPV vaccination (Gonzalez-Bosquet et al., 2020). Moreover, only 24 cases, accounting for 4.51% of cervical cancer patients, were found to be caused by high-risk genotypes not covered by the 9-valent vaccine. China and other 193 countries made the commitment to make sure that 90% of girls will be fully vaccinated by the age of 15 years in 2030 (Xia et al., 2020). However, the application of this vaccine is limited by low availability of imported vaccine and a long vaccination process (Yan et al., 2021). Although China has not integrated HPV vaccination into State immune programme, some provinces such as Fujian, Zhejiang and Guangdong have implemented free administration of domestic bivalent vaccine for girls under 15 years old since 2022. As a populous developing country, China’s national campaign on HPV vaccination is restricted by shortage of vaccine supply and high price of imported vaccine. Therefore, the development of sufficient and inexpensive domestic preventive HPV vaccines covering HPV16, 18, 31, 33, 39, 51, 52, 53, and 58 should be accelerated to achieved the goal.

The major limitation of our study was the fact that participants were enrolled from a single institution and not by randomized sampling of the population; therefore, the results might not be representative of all women in southern Hunan Province. In addition, some HPV-positive patients were lost to follow-up (e.g., attended other hospitals for morphological examination) and thus were not included in the morphological study, which resulted in a selection bias.

This study analysed the prevalence of HPV and the age-specific HPV genotype distribution during 2017–2020 in southern Hunan Province. Moreover, the relationships between HPV genotypes and cervical morphological lesions were also analysed. Overall, HPV prevalence was 14.59% showing a decreased trend compared to previous study in the region. Bimodal distribution of age-specific HPV infection rate demonstrated females aged ≤20 or >60 years were susceptible to HPV. Significantly, HPV 52, 16 and 58 were main genotypes occurred in cervical abnormalities. Additionally, Infection of HPV 31, 33, 39, 51, and 53 should not be ignored in the follow-up management. Our study provides epidemiological data for the development of domestic HPV vaccines and future national campaign on HPV vaccination.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Ethics Committee of the First Affiliated Hospital of University of South China. Written informed consent from the participants’ legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.

ZL designed the study and drafted the manuscript. HL performed the HPV analyses. JZ, RH, and QZ collected and reviewed the data. FY performed the statistical analysis and reviewed the manuscript. All authors contributed to the article and approved the submitted version.

This work was supported by The First Affiliated Hospital, Hengyang Medical School, University of South China.

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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