Cervical cancer (CC) is the fourth most common cancer among women globally (1). Globally in 2020, there were an estimated 604 127 CC cases and 341 831 deaths, with a corresponding age-standardized incidence of 13.3 cases per 100 000 women-years (95% CI 13.3–13.3) and mortality rate of 7.2 deaths per 100 000 women-years (95% CI 7.2–7.3) (2). CC is a global public health problem, with a particularly high burden in many low-income and middle-income countries (2), and is the most frequent gynecological cancer in developing countries (3). CC is also the leading cause of cancer-related deaths among women in low- and middle-income countries. Each year, China accounts for about 1/5 of the world’s CC incidence and deaths (4, 5). Moreover, the incidence and mortality of CC have shown an upward trend in recent years in China (6, 7). It has been one of the major threats to women’s health (6). Persistent high-risk human papillomavirus (HPV) infection is strongly and consistently associated with high-grade cervical intraepithelial neoplasia (CIN) acquisition and is considered essential for the progression of CC (8). Therefore, the study on CIN and CC is significant and deserves more attention.

In the early stages, CC is often asymptomatic; as CC progresses, nonspecific symptoms such as vaginitis and cervicitis may develop (9). Previous studies showed that persistent genital high-risk human papillomavirus (HPV) infection was the leading cause of CC (9). Okunade reported that about 99.7% of CC cases were caused by persistent genital high-risk human papillomavirus (HPV) infection (10). To reduce the incidence and mortality of CC, HPV screening and HPV vaccines for CC are becoming more and more widely used (11–13).

In 2009, the National Health Commission of the People’s Republic of China began to implement China’s National Cervical Cancer Screening Program in Rural Areas in some selected counties, which provides free screening for rural women aged 15-64 years and to encourage early diagnosis, detection, prevention, and treatment of CC (14, 15). In 2012, Hunan Province began implementing the Hunan Provincial Cervical Cancer Screening Program in Rural Areas (HPCCSPRA) in all counties, providing free CC HPV screening, diagnosis, and treatment for rural women aged 35-64.

Although there have been some studies on CC screening, diagnosis, and treatment (3, 16, 17), to the best of our knowledge, there are fewer studies on the incidence and distribution of CIN and CC based on long-term, large-sample population data, especially in Hunan Province, China.

Hunan Province is located in south-central China and covers a population of about 65 million. In this study, we conducted a systematic study using data from the HPCCSPRA (2020-2023) to describe the incidence and distribution of CIN and CC for rural women aged 35-64. This information may be useful for clinical counseling and early diagnosis of CC.

Overall, we have described the incidence and distribution of CIN and CC among rural women aged 35-64. To the best of our knowledge, previous studies rarely address this issue. The study was clinically relevant, and our findings may be useful for clinical counseling and early diagnosis of CC.

First, we have reported the incidence of CIN and CC for rural women aged 35-64. To the best of our knowledge, few studies have reported the incidence of CIN and CC for rural women aged 35-64 years based on a large population, including in China. Some studies have reported the overall incidence of CC, or the incidence of CIN, for women aged 35-64. For example, Gu et al. reported that the CC incidence was 0.28‰ for the total population aged 35-64 years in China (2000-2015) (24), and the CC incidence for women aged 35-64 years was about 0.56‰ (half of the total). It is consistent with the CC incidence reported in this study. Zhao et al. reported that the CC incidence was 26.54/100000, and the HSIL incidence was 223.89/100000 for women aged 35-64 years in rural areas in China (2018) (19); Shen et al. reported that the incidence of HSIL and CC was 395.6/100000 for women aged 35-64 years in Beijing City, China (2014-2015) (25); Lu et al. reported that the incidence of LSIL, HSIL, and CC was 1.89%, 0.60% and 0.03%, respectively, for women in minority area, Guangxi Province, China (2012-2019) (26); Shahmoradi et al. reported that the CC incidence among US women aged 35-64 years was from 14.38/100000 to 25.51/100000 (2001-2019) (27); Cleveland et al. reported that AIS incidence for women aged 40-64 years was about 2.4/100000 to 3.4/100000 (US, 2008-2015) (28). There are significant differences between these studies and the present study. On the one hand, it may be associated with differences in economic and medical conditions in different areas, which may affect CC screening and diagnosis rates (29). On the other hand, some previous studies were limited in study data, such as the study populations were from several hospitals, from small areas, or over a shorter period. To the best of our knowledge, no study has reported the incidence of CIN and CC in Hunan Province based on province-wide data. In addition, we have reported the incidence of CIN and CC by stages. It is of great significance for public health.

Second, among LSIL, HSIL, AIS, EICC, and ICC, there were significant differences in the proportion of previous pelvic examination and abnormal present pelvic examination, with a relatively low proportion of previous pelvic examination in EICC and ICC and a relatively high proportion of abnormal present pelvic examination in AIS, EICC, and ICC. It suggests that the more severe the CC, the more common the associated abnormal pelvic examinations are, but the lower the proportion of pelvic examinations. Moreover, it also suggests that women suffering from CC may be associated with a lack of pelvic examination. Previous studies support these findings (30). In this study, among LSIL, HSIL, AIS, EICC, and ICC, there was no significant difference in the proportion of vaginitis and uterine fibroid. At the same time, there were significant differences in the proportion of cervicitis and cervical polyp. The proportion of cervicitis was relatively high in AIS, EICC, and ICC, and the proportion of cervical polyps was relatively high in AIS. Overall, fewer studies address the above issues.

Although details of the negative population were not available in this study, if we regard LSIL as the reference, some previous studies were consistent with this study. For example, Long et al. reported that severe cervical inflammation was positively related to HSIL (31). Zhang et al. reported that cervical inflammation was a risk factor for cervical lesions (32). Zhao et al. reported that concurrent reproductive tract infections (such as cervicitis and cervical erosion) were risk factors for CC (33). Levy et al. reported an increased incidence of atypical squamous cells of undetermined significance, and atypical glandular cells not otherwise specified pap diagnoses were found in women with benign polyps on biopsy (34). Kucukyıldız et al. reported that endocervical polyps may be more common in patients with high-risk HPV infections (35). However, some previous studies were inconsistent with this study. For example, Brusselaers et al. found a causal link between vaginal dysbiosis and CC along the oncogenic human papillomavirus acquisition, persistence, and cervicovaginal dysplasia development pathway (36). Tao et al. reported that risk factors for HSIL included both Trichomonas vaginalis infection and cervical inflammation (37). The inconsistent results described above may be related to various factors (30, 38), such as different economic and medical conditions. Our findings suggest that there may be a correlation, perhaps a causal relationship, between CIN and CC and a broad range of abnormal pelvic examinations. It deserves in-depth research. Our findings may be useful for future in-depth studies.

Third, previous studies showed that almost all CCs are associated with HPV infection (10). In this study, we have presented the 13 high-risk HPV types for CIN and CC in detail, which have rarely been addressed in previous studies. HPV16 and HPV 18 were the most common high-risk types for all stages except for HSIL, and the more severe the CC, the higher the proportion of HPV16. It is consistent with previous studies (39, 40). However, there were significant differences in HPV types and proportions between this study and previous studies. For example, Muñoz et al. reported that HPV45 (4.4%) and HPV31 (3.4%) were common high-risk types (11 studies in nine countries, from 1985 to 1997) (40). Yang et al. reported that the most common high-risk HPV types were HPV52 (22.02%), HPV58 (12.79%) and HPV16 (12.60%) in LSIL; HPV16 (28.31%), HPV52 (20.63%), and HPV58 (17.73%) in HSIL; HPV16 (37.17%), HPV52 (13.77%), and HPV18 (8.39%) in EICC and ICC (Guangzhou City, China, 2015-2021) (41). Zhang et al. reported that the most common high-risk HPV types were HPV52 (20.31%), HPV16 (16.81%), HPV58 (14.44%), HPV18 (6.44%), and HPV53 (5.76%) in CIN1 (LSIL); HPV16 (45.69%), HPV58 (15.50%), HPV52 (11.74%), HPV33 (9.35%), and HPV31 (4.34%) in CIN2/3 (HSIL) (China, 2000-2019) (42). Cleveland et al. reported that HPV16 was the most frequently detected high-risk type in both AIS (57%) and CIN3 (58%), whereas HPV18 was the second most common high-risk type in AIS (38%) and less common in CIN3 (5%) (US, 2008-2015) (28). It is inconsistent with this study. These differences may be related partly to the fact that detailed HPV types were not reported in many cases, especially in LSIL and HSIL. It may lead to difficulties in comparing this study with other studies. It is a shortcoming in this study. However, due to the large sample size and comprehensive presentation of various HPV types in this study, this remains an important reference, for example, for vaccine research (43).

Fourth, compared to LSIL, the proportion of EICC and ICC was relatively high in women aged 55-64; the proportion of AIS, EICC, and ICC was relatively low in women with university and above. Details of the negative population were unavailable in this study. If we regard LSIL as the reference, we would get the following findings: the proportion of severe CC was relatively high in the older age groups and relatively low in women with high education levels. It is consistent with previous studies (26, 32, 37, 44, 45). The proportion of severe CC was relatively high in the older age groups, possibly associated with several factors. On the one hand, in the early stages, CC is often asymptomatic, resulting in most women not being screened or examined (9, 46). When severe CC appears, it often develops over a long time. On the other hand, women’s economic conditions, medical conditions, and health knowledge increase with age, increasing CC screening rates (4, 29, 47, 48). Compared to older women, younger women may lack systematic screening and pelvic examination. The proportion of severe CC was relatively low in highly educated people, which may be mainly associated with better health knowledge and economic conditions. Health knowledge is one of the main factors in CC screening; a higher level of education and confidence that any potential symptom would be identified were associated with increased awareness (47–50). Education level is associated with economic conditions, which may have an important impact on CC screening, diagnosis, and treatment (29, 51). Women with high education levels may access earlier screening and diagnosis of CC, reducing the proportion of severe CC.

Some things could be improved in this study. First, due to data limitations, some demographic characteristics, such as economic conditions and ethnic groups, were not included in this study. In addition, there is no detailed information on the medical cost of CIN and CC. Second, detailed HPV types were not reported in many patients, especially in LSIL and HSIL, which may lead to difficulties in comparing this study with other studies. Third, this study focused on the pelvic examination and epidemiology of patients. Due to the lack of detailed information on the negative population, we could not conduct some analyses, such as calculating the incidence of CIN and CC by age and education level and analyzing risk factors for CIN and CC. Fourth, all the patients in this study were women with high-risk HPV. However, although almost all CINs and CCs are associated with high-risk HPV, there are still some that may not be associated with high-risk HPV. Therefore, the incidence of CIN and CC may be slightly underestimated.

Despite some limitations, this study is still of great significance. On the one hand, this study involved many people and covered a wide area, which was well representative. On the other hand, the research limitations pointed out above also provided directions for further in-depth research, and our findings may be useful for future in-depth studies.

We have described the incidence and distribution of CIN and CC among rural women aged 35-64. These findings were clinically relevant and were useful for clinical counseling and early diagnosis of CC.