Introduction
Cervical cancer ranks fourth among malignant tumours in women worldwide. The prevalence rate is increasing annually and has affected young people. In 2018, the World Health Organization (WHO) launched a call to accelerate the elimination of cervical cancer as a global public health problem. In recent years, regional differences have been observed in cervical cancer screening. Specifically, the screening coverage, testing methods and post-screening management differ among high-, middle- and low-income countries. This situation reflects complex factors related to the economic strength of the government, organised population-based programs, monitoring and quality assurance measures and female participation rates [
1‐
3]. In 2009, China launched a national public health program to curb cervical cancer [
4]. In comparison with high-income countries, cervical cancer prevention in China remains unsatisfactory. Adequate diagnosis, follow-up and management of positive results are needed for a more effective screening [
2]. The Chinese government’s current efforts to implement an organised population-based screening program and reasonable post-screening management will lead to more positive results [
5,
6].
Human papillomavirus (HPV) is a double-stranded DNA virus (without an envelope) of the papillomavirusidae [
7]. It is highly contagious and can infect the human epidermis and mucous membrane, leading to cervical intraepithelial lesions and cervical cancer [
8]. In terms of pathogenicity, HPV viruses can be classified as high- or low-risk types. The high-risk type is closely related to various cervical intraepithelial neoplasias, cervical cancers and other malignant lesions [
9]. By contrast, the low-risk type is mainly involved in multiple benign lesions of the external genital tract [
10].
Cervical cancer screening methods include conventional cytology, liquid-based cytology, visual inspection with acetic acid, nucleic acid testing and cytology based on Romanovsky-Giemsa staining. However, HPV nucleic acid testing, especially high-risk HPV, has shown greater advantages in improving the detection rate of cervical intraepithelial neoplasia (CIN) 2+ and reducing the incidence of cervical cancer [
11‐
13]. High-risk HPV is closely related to cervical cancer. Approximately 70% of cervical cancer and pre-cancerous lesions are associated with HPV16 and HPV18 [
14]. However, the predominant HPV genotypes may result in different outcomes at different stages of the disease [
15,
16]. HPV52 and HPV16 are dominant in CIN1, while HPV16 and HPV58 are found in CIN2/3 [
17]. Cervical cancer has been linked to persistent infection with high-risk HPV [
18,
19]. Therefore, regular HPV detection is a critical measure to prevent and treat HPV-related diseases. If HPV16 or HPV18 infection is detected, colposcopy is also required to obtain accurate diagnostic information [
20,
21].
The epidemiological characteristics of cervical cancer vary remarkably across different geographical locations. Approximately 90% of the world’s cervical cancer occurs in countries without effective HPV screening and vaccination [
22]. However, formal screening programs have benefited many countries, and cancer prevalence and mortality have decreased by more than half in the past 30 years [
22,
23]. Therefore, organised cervical cytology, pre-invasive disease treatment and vaccination are key measures to reduce the incidence of cervical cancer. High-priced HPV vaccines can protect against more HPV subtypes. However, due to limitations such as price and quantity, the optimal vaccination time should not be missed by blindly pursuing high-priced vaccines. Vaccine distribution should be effectively and rationally distributed according to HPV epidemiological characteristics in different regions. Information from (regular, large) HPV screening is needed to corroborate with the epidemiological results. However, limited studies have reported the characteristics of HPV infection in Putian City, Fujian Province in the past decade. Investigating the epidemiology of HPV in this region is of great help in choosing vaccines effectively. In this study, the results of large-scale female HPV high-risk infection screening in Putian City in the past 2 years were collected to explore the status of high-risk HPV infection and the distribution of genotypes in this region. Ultimately, this study aimed to provide a practical reference for the epidemiology, diagnosis, treatment and vaccination of cervical cancer in this region.
Materials and methods
Study population
The data for this study were obtained from the Chinese government’s public health program (“Cervical and Breast Cancer Screening Project”), under which regular tests are conducted every year. The present survey was conducted in Putian City, Fujian province. A total of 40,693 females who were screened for high-risk HPV at the Affiliated Hospital of Putian University from July 2020 to December 2021 were enrolled. The age range was 30–70 years (50.1 ± 7.9). The inclusion criteria are as follows: no history of hysterectomy or cervical surgery, no severe endocrine or autoimmune diseases, abstinence before the examination, no vaginal administration and non-pregnancy. The exclusion criteria are as follows: incomplete information, history of cervical conization and hysterectomy, history of cervical treatment in the last 3 months, acute reproductive tract inflammation, elimination of secondary re-examination data and exclusion of common gynaecological diseases (e.g., cervical cancer, ovarian cancer and uterine leiomyoma). All tests were performed with the informed consent of the enrolled women. This study was approved by the Ethics Committee of the Affiliated Hospital of Putian University (202224).
Specimen collection and HPV genotyping
Cervical samples were obtained from women by using a cytobrush according to the instructions, and the samples were used for genomic DNA extraction. The samples of cervical exfoliated cells were thoroughly vortexed and mixed. Then, 350 µl of liquid was absorbed into the nucleic acid extraction reagent. HPV DNA was extracted using a nucleic acid extractor. DNA (5 µl) was mixed well with amplification reagent (20 µl). After capping the amplification tube and quick centrifugation, the PCR amplification reaction was carried out via real-time fluorescence quantitative PCR. All procedures were performed strictly according to the kit’s instructions.
ThinPrep cytologic test (TCT)
Specimens that were positive for HPV genotyping were directly used for TCT. Two experienced cytopathologists independently diagnosed the liquid cytology specimens. A third cell pathologist reviewed the sample when the diagnosis of the two cytopathologists differed. According to Bethesda’s system, cytological results were classified into negative for intraepithelial lesion and malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) [
24].
Statistical analysis
Data were analysed using GraphPad Prism 7.0 software. An interval of 95% confidence (95% CI) was calculated for HPV prevalence. The χ2 test was applied to compare the infection rate of different age groups and the infection rate of high-risk genotypes according to additional TCT classifications. Differences were considered statistically significant if the difference was P < 0.05.
Discussion
Malignant tumours of the female reproductive tract are prevalent in developing countries [
25]. Since the introduction of cervical cancer screening in China in 2009, the incidence and mortality of cervical cancer in Chinese women have decreased. However, the prevention and treatment of cervical cancer in China has not obtained promising results, and cervical cancer has become prevalent in young people [
26,
27]. Globally, young women (< 25 years of age) are prone to peak HPV infection rates, whereas a second peak in older women has been observed in regions such as China, East Africa and Latin America [
28‐
30]. A second peak in invasive cancers used to be seen (in the UK) in the early 1990s, but this has largely disappeared as screening has detected and treated much of the CIN in younger women. There was still a small rise in 60–70 year old women [
31]. HPV infection plays an essential role in the development and occurrence of cervical cancer. However, the HPV infection rate varies among different countries and regions [
32], which may be related to the geographical location, living environment and living habits of the resident population [
33,
34].
This study was a large-scale HPV screening study among women in the region, and the results were closely related to the unique research population. Results showed that the overall HPV infection rate in the regular screening population was 9.6%, which was significantly lower than the HPV infection rate in women who visited the gynaecology department of hospitals [
35,
36]. Although the hospital (gynaecology) patients were a selected group and were therefore likely to have a higher overall rate of HPV positive testing, the trends with age were the same in both the general population and the hospital population [
33,
37,
38]. These conditions may be related to the lack of detection and treatment of HPV infection and precancer at an earlier age. Associations were observed among HPV infection and education, smoking, social behaviours and rurality [
24,
39]. In the present study, the infection rate of high-risk HPV in women was also consistent with this characteristic. The infection rate people aged 50–70 years was higher than the overall infection rate, suggesting that middle-aged and older women had a high risk of HPV infection. The infection rates of high-risk HPV52, HPV58 and HPV16 increased with age, and HPV52 was the genotype with the highest infection rate, consistent with Taiwan and southern China [
38,
40] but different from the United States [
41]. The infection rate of HPV16 only ranked third in the present study.
Notably, the 60–70 year age group had the highest HPV infection rate, and compared with the previous groups, the single infection rate was the lowest, while the multiple infection rates were the highest. This condition may be related to decreased body immunity and the reactivation of menopausal latent HPV [
42,
43]. Multiple infections in 60–70 group might represent more than one episode of infection as well as a multiple infection. Women in this group are likely to show persistent HPV infection [
25,
44] and have a high risk of cervical cancer. Therefore, it comprehensive and regular cervical screening should be strengthened for HPV-positive middle-aged and older women [
22,
44,
45].
This study also deeply analysed the relationship between cervical cytology and HPV infection. The results showed that with the increase in age group, the risk of malignant transformation of cervical cells (≥ ASC-US) in HPV-positive people gradually increased, thus confirming the high risk of cervical cancer in middle-aged and older women. Interestingly, the proportion of high-risk genotypes differed in different stages of cervical cytological abnormalities. For example, HPV16 ranked first in HSIL and only ranked third in non-HSIL. The HPV52 phenotype was opposite to that of HPV16. HPV16, HPV52 and HPV58 were the top three types of CIN in China [
17]. This study suggested that the infection rates of HPV16, HPV52 and HPV58 were closely related to the severity of cervical cytology, which was consistent with previous views [
17]. The results of this study have specific auxiliary reference value for clinicians to evaluate the progression of cervical cancer.
This study retrospectively analysed the characteristics of high-risk HPV infection, genotype distribution and cervical cytology in 40,693 women in Putian, but this study has some shortcomings. First, the data were derived from the screening results in the past 2 years, and long-term dynamic observations are lacking. Moreover, considering the limited sample size, the results might not accurately reflect the epidemiological characteristics of HPV in the whole region. Therefore, in a follow-up study, the sample size will be expanded, and the monitoring time will be extended. Second, the HPV detection kit could detect 14 high-risk genotypes. Although it contained the standard typing of the Asian population, not enough types of typing were used, and a risk of missed detection was involved. Third, the women included in this study were aged 30–70. However, a few investigations have focused on HPV infection in people under 30 years old, especially those under 20 years old, which is not conducive to the epidemiological study of HPV in the whole female population.
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