Human papillomavirus (HPV) is a non-enveloped, double-stranded circular DNA virus with a genome size of approximately 8 kb. It belongs to the Papillomaviridae family and Alphapapillomavirus genus. As one of the most common sexually transmitted infections, HPV enters through minor abrasions in the skin or mucosa during sexual contact and infects basal epithelial cells (1). Approximately 70% of sexually active women will acquire an HPV infection during their lifetime (2). Fortunately, most cervical HPV infections—whether accompanied by cytological abnormalities or not—are cleared or suppressed by the cellular immune response within 1 to 2 years after initial exposure (3). However, persistent infection occurs in about 10% of cases, significantly increasing the risk of developing precancerous lesions (4). Not all HPV genotypes are carcinogenic. Low-risk HPV types (LR-HPVs) primarily cause benign genital warts and skin lesions, whereas high-risk HPVs (HR-HPVs) can lead to oropharyngeal cancers (affecting the oral cavity, tonsils, and throat) and various anogenital cancers, including cervical, anal, vulvar., vaginal, and penile cancers. Specifically, 15 genotypes—16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82—are classified as high-risk (HR), while 12 genotypes—6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108—are considered low-risk (LR) (5). The carcinogenic mechanism of HPV is primarily associated with two oncoproteins it encodes, E6 and E7. These two proteins work synergistically to promote cell proliferation, extend the cell life cycle, and prevent apoptosis. This ultimately leads to uncontrolled cell division and the accumulation of genetic damage (6). Persistent infection with high-risk HPV (HR-HPV) is strongly associated with the development of cervical cancer, accounting for approximately 98.7% of cases (7). Among these, HPV-16 and HPV-18 are the most carcinogenic types, responsible for about 70% of cervical cancer cases and 50% of cervical intraepithelial neoplasia grade 3 (CIN3) cases (8). In contrast, low-risk (LR) HPV-6 and HPV-11 cause approximately 90% of genital wart cases.

The HPV is a necessary but not sufficient cause of cervical cancer (2). Other significant co-factors include certain sexually transmitted infections (such as HIV and Chlamydia trachomatis), smoking, multiple childbirths, and long-term use of oral contraceptives (9). Globally, cervical cancer ranks as the fourth most common cancer and the fourth leading cause of cancer-related deaths among women globally, posing a major public health challenge. According to recent global statistics, there are approximately 604,000 new cases and 342,000 deaths annually, with the majority occurring in sub-Saharan Africa, Melanesia, South America, and Southeast Asia (10). Nearly 70% of the global cervical cancer burden is observed in less developed countries. As a developing country, China reports around 109,741 new cervical cancer cases and approximately 59,060 deaths each year, accounting for 18.2% of global new cases and 17.3% of global deaths, respectively (11). Cervical cancer is not only one of the most frequent and severe cancers among women in many developing regions, but its societal impact is further exacerbated by the relatively young average age at death—often during child-rearing years. Moreover, cases are frequently diagnosed at advanced stages due to inadequate or absent screening programs. Therefore, eliminating cervical cancer remains a critical global public health challenge.

Cervical cancer is a highly preventable and, if detected early, readily treatable disease. However, it remains a persistent major challenge in low- and middle-income countries that lack systematic screening and prevention programs. There is robust evidence that HPV vaccination is not only effective but also cost-effective (12–14). Nevertheless, various obstacles hinder the promotion and implementation of these measures across different countries (15). China, for instance, introduced the HPV vaccine relatively late and has not yet included it in the national immunization program. Data from 2021 show that the HPV vaccination rate among females nationwide was only 3%, with just 1.9% of girls aged 9–14 vaccinated (16). In response to the World Health Organization’s (WHO’s) global call to eliminate cervical cancer, many regions in China are implementing free HPV vaccination programs under the “Healthy China 2030” initiative. These efforts currently focus on specific groups, such as 13–14-year-old girls in Chengdu, with plans to gradually expand coverage. Despite this, economic and psychosocial factors continue to hinder broader vaccine uptake (16).

In the realm of screening, HPV testing allows for the screening interval to be extended to up to 5 years or longer, owing to its high sensitivity and stable negative predictive value. Therefore, the WHO recommends it as the primary screening method (15). Despite continuous improvements in China’s cervical cancer screening system, the coverage rate remains low. The screening rate for Chinese women aged 35–44 is only 43.4% (17), which falls far short of the WHO’s 70% target (18).

Cervical cancer is a malignant tumor that poses a serious threat to women’s health and lives globally. Effective control and prevention measures are imperative both worldwide and in China. Against this backdrop, HPV genotyping data in Chengdu region are extremely scarce. As the largest women and children’s medical center in southwestern China, CWCCH has a service network covering the entire Chengdu area and a wide range of patient sources. The prevalence of HPV diseases in this hospital is highly representative of the region. Therefore, this study is based on the HPV screening data of 51,556 women at this hospital, aiming to provide more targeted strategies for the prevention, treatment, and eventual elimination of cervical cancer and HPV-related diseases.

This cohort study, based on 51,556 female HPV screening cases in the Chengdu region from 2020 to 2024, comprehensively analyzed HPV genotype distribution, infection patterns, temporal trends, and age-specific characteristics. HPV prevalence demonstrates significant geographical variation, with a global estimated prevalence of 11.7% (20). The overall HPV prevalence in this study was 22.03%, showing a significant decrease compared to the historical data from our institution covering the eight-year period prior to 2020 (23.28%, n = 181,705; χ² = 35.065, p < 0.001) (21). However, trend analysis revealed an upward trend in the annual infection rate between 2020 and 2024, driven particularly by increases in high-risk genotypes such as HPV-16, HPV-31, HPV-51, HPV-52, HPV-56, HPV-68, and HPV-73.

Geographically, the prevalence rate found in this study was comparable to that of Zhejiang Province (22.3%) (22), which has a similar level of economic development (p > 0.05), but was significantly higher than the overall prevalence among Chinese women (17.70%) (23) and that in more economically developed cities such as Beijing (20.15%) (24), Shanghai (18.81%) (25), and Guangzhou (19.78%) (26) (all p < 0.05). These disparities may be attributed to a combination of geographical, socioeconomic, behavioral, and cultural factors. Furthermore, it is important to note that the timeframe of this study (2020–2024) spans the COVID-19 pandemic period. The lower infection rate observed in early 2020 may have been partly attributable to interruptions in women’s HPV screening behaviors and healthcare-seeking patterns due to isolation measures during the pandemic, while the upward trend in subsequent years may include a “catch-up screening” effect. The design of this study does not allow for quantification of this impact, which should be considered as an important contextual background when interpreting temporal trends. The design of this study does not allow for quantification of this impact, which should be considered as contextual background when interpreting temporal trends. As studies have found a strong correlation between HPV prevalence and cervical cancer disease burden (20), the high infection rate and the rising trend of specific HR genotypes in Chengdu constitute a significant public health warning and underscore the substantial challenges that remain in achieving the WHO’s 2030 cervical cancer elimination goal in this region.

This study found that the HPV infection rate among gynecological outpatients (25.46%) was significantly higher than that in individuals undergoing routine health examinations (13.97%) (p < 0.05). This finding is consistent with a report from Beijing (21.0% vs. 11.9%) (24), which can be attributed to the presence of genital tract infections or lesions in gynecological outpatients, whereas individuals in the general health screening population typically have normal genital tract conditions. Seasonal changes can influence disease distribution by affecting biological functions such as host susceptibility, metabolism, and inflammatory responses (27). This study is the first to observe a distinct seasonal variation in HPV infection rates: the rates in spring, summer, and autumn were significantly higher than in winter (p < 0.05), while no significant differences were observed among the first three seasons (p > 0.05). This finding differs from a study conducted in Zhejiang (22), which reported the highest HPV infection rates in winter and spring. The climatic differences during winter between the two regions may be one reason for this discrepancy: lower temperatures in Chengdu may partially inhibit virus survival and transmission. Currently, there is no strong biological evidence to support a clear seasonal pattern in HPV infection. Therefore, this finding should be considered preliminary, requiring further validation across different regions and study designs, and interpreted with caution.

This study identified the most prevalent HR-HPV genotypes in the Chengdu region as HPV-52, HPV-16, HPV-58, HPV-51, and HPV-39. Compared to the genotype distribution from our institution 8 years ago (52, 16, 58, 53, 51) (21), four genotypes (52, 16, 58, 51) remained consistent, with only genotype 39 replacing 53, reflecting minor shifts within an overall stable local HPV genotype distribution. Horizontal comparison revealed that the dominant genotype profile in this study was completely consistent with findings from Beijing (52, 16, 58, 51, 39) (24), but differed from the large-scale data across 29 provinces in China (52, 16, 53, 58, 51) (28), as well as studies from Shanghai (52, 16, 58, 53, 39) (25), Guangzhou (52, 58, 16, 51, 39) (26), and Zhejiang (52, 58, CP8304, 16, 51) (22). Comprehensive analysis indicates that HPV-16, HPV-52, and HPV-58 are the dominant viral strains nationwide (21–26, 28). This study further confirms that HPV-52 and HPV-58 are particularly common genotypes in the Asian region. These prevalence disparities reflect both regional epidemiological variations and potential differences in the sensitivity and types of HPV detection kits used for specific genotypes (29).

In terms of carcinogenic risk, HPV-16 carries the highest risk, followed by HPV-18, while other Alpha-9 species members (such as 31, 33, 35, 52, 58) are classified as medium-risk (30). A large-scale study focusing on Chinese patients with invasive cervical cancer (ICC) revealed that the top five HPV types are 16 (62.5%), 18 (12.4%), 58 (8.6%), 52 (5.7%), and 33 (4.6%) (31). The genotype prevalence ranking in our study indicates that HPV-16, 52, and 58 not only have high prevalence rates but also strong carcinogenicity; whereas HPV-18, 31, 33, and 35, despite their relatively lower prevalence, also pose high carcinogenic risks. It is noteworthy that beyond HPV-16 and 18, HPV-52 and 58 collectively account for 13.3% of cervical cancer cases in China (31). Cervical cancer risk is determined by both the specific HPV types involved and insufficient screening coverage. The 33.06% detection rate (4,937 genotype-positive cases) of HPV-16, 52, and 58 identified in this study highlights the crucial importance of implementing targeted vaccination and systematic screening as fundamental strategies for cervical cancer control.

Among the five vaccines currently approved in China (21), only Gardasil® 9 covers types 16, 52, and 58 simultaneously. Promisingly, domestic vaccine development is progressing rapidly: two Shanghai-based institutes have vaccines in clinical trial stages—a non-avalent vaccine (covering types 6, 11, 16, 18, 31, 33, 45, 52, 58) and a quadrivalent vaccine (targeting 16, 18, 52, 58) (32). These candidate vaccines will better meet the protection needs of women in China and other Asian regions, as types 52 and 58 are predominant circulating strains in this area. In summary, among the currently available vaccines, Gardasil® 9 can prevent the three most common HR genotypes (HPV-52, HPV-16, and HPV-58) in this region, and its protective scope is significantly superior to the quadrivalent vaccine, which only covers types 16, 18, 6, and 11. Therefore, Gardasil®9 is currently the option that best aligns with the specific preventive needs of the female population in Chengdu, China.

This study revealed a typical bimodal age-specific distribution of HPV infection rates. The first peak occurred in the ≤20 years age group, with a prevalence rate as high as 49.35%; subsequently, the infection rate gradually declined and stabilized during middle age; and a second, smaller peak emerged in the ≥61 years age group, with a prevalence rate of 30.79%. This bimodal pattern is consistent with the findings of numerous global studies (20–26). The first peak among young women often occurs shortly after sexual debut (around age 15) (33) and is primarily associated with factors such as an immature immune system and relatively high sexual activity (20). It is noteworthy that most infections at this stage are transient; approximately 80–90% are cleared by the body’s immune system within 1 to 2 years (34). To effectively address this early infection peak, completing vaccination before female sexual debut has been proven to be the most cost-effective key strategy – as existing vaccines cannot treat established infections or lesions, and cross-protection effects in vaccinated populations are limited, preemptive prevention is particularly important. A cohort study covering 179 countries and 58 million 12-year-old girls confirmed that vaccination could prevent 690,000 cases of cervical cancer and 420,000 deaths in their lifetime, with a cost per disability-adjusted life year (DALY) averted lower than the per capita GDP, demonstrating favorable health economic benefits (14). A further US study based on health insurance data also showed significantly reduced incidence of genital warts, cervical cytological abnormalities, and high-grade cervical intraepithelial neoplasia (CIN) among vaccinated females aged 14–19 (35), strongly validating the practical effectiveness of this strategy.

To effectively address the second infection peak in middle-aged and older women, it is crucial to continuously promote regular cervical cancer screening. Given that the HPV infection rate in this study stabilized around age 30, and persistent infection is a major risk factor for cervical cancer in women of this age group (36), screening can not only reduce precancerous lesions and clear persistent infections but may also prevent subsequent infections through an antigen presentation effect (37). The WHO’s Cervical Cancer Elimination Strategy sets a 2030 target of achieving 70% high-performance screening coverage for women at ages 35 and 45, and providing treatment for 90% of identified precancerous lesions (18). However, current screening coverage remains suboptimal, particularly in low- and middle-income countries – a global study covering 202 countries showed that two-thirds of women aged 30 to 49 have never been screened for cervical cancer, and these regions also bear the highest disease burden (9). In terms of screening strategy, the HPV genotyping-based approach holds significant value. Research indicates that HPV genotyping can enable approximately 13.2% of those screened to qualify for an accelerated treatment pathway (38), and it is comparable in safety to the traditional multiple-visit colposcopy follow-up model while requiring fewer screening visits, making it particularly suitable for resource-limited settings (39). Furthermore, in response to the observed resurgence in infection rates among women aged ≥61 years identified in this study, it is essential to emphasize the importance of continuous screening until age 65, stopping only after meeting specific exit criteria (30). Effective screening and treatment are expected to significantly reduce the HPV-related disease burden in this age group (36).

In summary, to comprehensively address the dual-peak challenge of HPV infection, it is necessary to promote adolescent vaccination to control the first peak while simultaneously strengthening screening coverage and standardization across all age groups – particularly among middle-aged and older women – to establish a dual prevention system of “vaccination and regular screening.” With the widespread adoption of HPV vaccination and the promotion of HPV-based screening strategies, cervical cancer has the potential to become a rare disease in the coming decades (40).

Of the 11,360 HPV-positive cases in this study, single infections were predominant (76.47%), while multiple infections accounted for 23.53%. This distribution pattern is highly consistent with previous studies, which typically report single infection rates ranging from 70 to 80% and multiple infection rates between 20 and 30% (21–26). Further analysis revealed that mixed high-risk and low-risk (HR + LR) infections accounted for 12.29% of all HR infections (including single HR infections and HR mixed infections) and 39.40% of all LR infections (including single LR infections and LR mixed infections). These findings have clear clinical implications: assuming all HR types have carcinogenic potential and all LR types primarily cause genital warts, clinicians managing a cervical cancer patient have a probability of approximately 12.29% of detecting a concurrent low-risk HPV infection. More importantly, conversely, when diagnosing a patient with genital warts, there is a significantly higher probability of approximately 39.40% of concurrently detecting a HR HPV infection. Therefore, it is strongly recommended that clinicians perform HPV genotyping before and after treating patients with genital warts (particularly prior to procedures such as excision) to accurately identify and assess potential mixed infections with HR types, thereby enabling more comprehensive risk evaluation and patient management.

The occurrence of single or multiple HPV infections in women and their associated risks is a complex issue involving multiple factors. On one hand, viral factors are evident: different HPV subtypes can infect the cervical mucosa through shared pathways, and the inherent infectivity of each genotype varies—this study confirms that certain high-risk types (e.g., HPV-52 and HPV-16) dominate in both single and multiple infections. On the other hand, host factors are critical, as an individual’s immune status and genetic susceptibility determine their risk of infection with specific HPV types (41). Furthermore, epidemiological studies indicate that the probability of multiple infections is higher among young, sexually active women with multiple sexual partners, and their subsequent risk of developing related diseases is significantly increased (42). Regarding carcinogenic risk, there is still no consensus in the academic community. Some studies have shown that, compared to single infection, multiple infections can increase the risk of cervical cancer by up to 11.9 times and are considered an important risk factor for high-grade cervical intraepithelial neoplasia (CIN2+) (43, 44). However, other viewpoints suggest that the severity of lesions depends primarily on the inherent carcinogenic potential of the high-risk types involved, rather than on the number of types infected (45). It is worth noting that potential biological interactions among different HPV types in multiple infections, as well as differences in the host immune microenvironment, may contribute to the inconsistency in research conclusions. In summary, whether there is an essential difference in carcinogenic risk between single and multiple HPV infections still requires further investigation and validation through more refined molecular epidemiological studies and long-term follow-up data.

This study has several limitations. First, as a retrospective analysis conducted at a single medical center with participants primarily consisting of women seeking healthcare services, potential selection bias exists, and caution is warranted when generalizing the findings to the general female population in Chengdu. Second, the lack of key behavioral data (e.g., detailed sexual history) and HPV vaccination history limited further in-depth attribution analysis of the observed infection patterns and trends. Furthermore, this study did not correlate HPV infection status with cervical cytological or histopathological outcomes, thus precluding assessment of the association between various infection statuses and the subsequent risk of developing clinical lesions.

In this study, although the overall HPV prevalence rate (22.03%) showed a significant decrease compared to historical data from 2013 to 2020 (23.28%; χ² = 35.065, p < 0.001), a continuous rebounding trend has been observed since 2020. HPV-52, HPV-16, and HPV-58 were identified as the three predominant high-risk genotypes, dominating the regional HPV epidemiology. A distinctive bimodal age distribution was characterized by a first peak in adolescents and young women aged ≤20 years (49.35%) and a second peak in older women aged ≥61 years (30.79%). Notably, this study is the first in this region to identify significant seasonal variation, with significantly higher HPV prevalence rates in spring, summer, and autumn than in winter. The study revealed that a substantial proportion (39.40%) of LR-HPV infections were actually HR-LR mixed infections. This finding strongly suggests that comprehensive HPV genotyping for patients with genital warts—particularly prior to procedures such as excision—is crucial for clinicians to identify potential high-risk type co-infections, thereby enabling more accurate risk stratification and follow-up management. To address the first infection peak in young women, priority should be given to promoting the 9-valent vaccine covering HPV-16/52/58, especially before sexual debut. To effectively reduce the second infection peak in older women, it is essential to strengthen systematic cervical cancer screening for middle-aged women and maintain screening until at least 65 years of age in accordance with international guidelines. This study has several limitations, including its single-center retrospective design, lack of vaccination and sexual behavior data, and failure to integrate cytological or histopathological results to assess disease progression risk. To effectively reduce the cervical cancer burden in Chengdu and similar regions, a dual strategy combining precision vaccination with strengthened screening across all age groups must be implemented.