This is one of the few nationwide investigations of high- and low-risk HPV in a large-scale screen of the Chinese population. Because of regional differences, the population composition, and the sampling periods, the reported prevalence varies from study to study, but the most the heavily burdened HPV regions are Sub-Saharan Africa (24.0 %), Eastern Europe (21.4 %), Latin America (16.1 %), and Southeastern Asia (14 %) [25]. In this present survey, the overall hrHPV-positive rate was 21.07 % (95 % Cl 20.83–21.31 %), which increased in levels within HPV-heavy-burden countries and was higher than the average global level.

It is possible that the variable HPV prevalence in China occurs because of the large Chinese population and its territories. Meanwhile, economic conditions, cultural habits, and population migrations have affected Chinese lifestyles and health [11, 15, 26]. Based on population-based screening results that have been previously reported, the overall prevalence of hrHPV varies from 9.9–27.5 % in China [15]. The highest infection rate is in Shanxi, a region with a heavy burden of cervical cancer in China. By contrast, the lowest infection rate was detected in Beijing, the capital of China with prosperous economic and more robust healthcare system. The infection rates in other regions were ~15–20 %, and a pool analysis that included 17 populations from 9 regions showed that the positive rate of hrHPV infection was 17.7 % [27]. Together, the overall hrHPV-positive rate in this present study was found to have increased slightly.

Compared with region-based data, the rates obtained in this present study were higher than those previously reported for Shanghai [28, 29], Shenyang [28], Guangdong [30, 31], and Hangzhou [32] (Additional file 1: Table S5). Additionally, some newly studied regions in this present survey showed high hrHPV incidences, for example HaiKou (31.94 %) and Chongqing (27.29 %), and several cities in the North, including Jinan, Jilin, and Tianjin. These data showed that hrHPV infection is becoming more serious, as the infection rate is increasing in many regions, and some of those regions may soon reach the level of a heavy burden of infection. Notably, great advances in screening strategy and laboratory methods could also have partially contributed to the increased prevalence.

Regarding the hrHPV prevalence in different age groups, a meta-analysis conducted by Bruni et al. [25] showed a bimodal age distribution, with the peak of HPV infection occurring within a younger age group (just after beginning sexual relations). Globally, the lower prevalence of infection in the middle age group was accompanied by a gradual reduction in the incidence in developing countries or a second peak in developed countries [25]. The trend wherein hrHPV infection shows high rates in younger groups and low rates in middle age groups reflects the natural history of HPV infection. Young females are sensitive to HPV soon after beginning of sexual activity because of immature immune protection. Nevertheless, most cases of HPV infection are usually temporary, so in 70 % and 91 % of women infected with HPV, the virus could be cleared within one or two years, respectively [33]. The slight increase in the HPV infection rate in older females might reflect the viral persistence or reactivation of latent HPV, likely because of the physiological and immunological disorders that can result from hormone fluctuations during the menopausal transition [34]. In this study, the general age distribution showed a first peak of hrHPV in the age group of 15-year-old patients (30.55 %), then gradually decreasing in middle age, which is consistent with data from Bruni et al. [25]. However, the hrHPV infection rate was significantly increased in 50–60-year-old individuals compared with women in their 40s, which is a similar trend that has been observed in most developed countries. The prosperous economy in most major cities could influence the culture and sexual behavior of Chinese individuals [15]. Nonetheless, the exact mechanisms for the increase in HPV prevalence still remain unclear.

Data concerning the distribution of HPV genotypes is important for both vaccine development and HPV-based screening design, particularly for selecting the testing spectrum of HPV genotypes [35] and detecting multiple HPV infections. It is a prerequisite for the genotyping assays in cervical cancer screening programs. However, few HPV devices have been cleared by the FDA, including the Roche Cobas 4800, which also provides limited genotyping data [36]. Therefore, the Tellgenplex™ HPV DNA Test, an established genotyping method [23], was performed in this survey. By following CAP (College of American Pathologists) principles, the validation of Tellgenplex™ HPV DNA Test were conducted compare to HCII in the molecular biology lab of KingMed, and the correlations that we detected were found to be (coincident rate = 90.5 %, Kappa = 0.88).

Consistent with the data generated by some Chinese population-specific investigations, HPV16, HPV52, and HPV58 were found to be the dominant hrHPV types [37, 38]. Compared with the data of Wu et al. [28], a population-based investigation from five regions (Beijing, Shanghai, Xinjiang, Henan, and Shangxi) in China, the infection rates of HPV16 (4.82 %), HPV52 (4.52 %), and HPV58 (2.74 %) were all higher than in the HPV16 (2.9 %), HPV52 (1.7 %), and HPV58 (1.5 %) strains obtained in this present study. Regarding the proportion of these three genotypes, except for HPV52 (16.9 % and 11.9 %, P = 0.006), which is higher than that reported in the present study, there were no significant differences detected in the proportion of HPV16 (20.2 % and 18.02 %, P = 0.245) or HPV58 (10.8 % and 10.23 %, P = 0.686). The proportion of HPV16 in this survey was even lower than that among the normal cytology samples reported by Guan et al. and Bruni et al. (20.4 % and 22.5 %, respectively) [25, 39]. Notably, HPV52 and HPV58 accounted for 27.13 % of infections, which is markedly higher than the global rate of 14.37 % [39]. Although both HPV52 and HPV58 were all common among Asian populations, the significance of the two genotypes remains unknown. Zhao et al. [40] reported that HPV52 infections are more common among healthy individuals, whereas HPV58 has been linked to cervical cancer. Some studies conducted in the South and West regions of China, which only included CIN or cancer samples, indicated that HPV58 is more prevalent than HPV52 [18, 30, 41, 42]. HPV18, apart from HPV16, is also important for cervical carcinogenesis [43]. However, in our present study, it was the seventh most common infection, and the infection rate (1.48 %) was in line with the study of Wu et al. (P = 0.871) [28]. These findings indicated that in addition to HPV16 and HPV18, the HPV vaccine in China should also include the HPV52 and HPV58 genotypes.

In addition to carcinogenesis, many benign cutaneous warts, mucosal lesions, and low-grade cervical intraepithelial lesions generate a considerable health burden that is associated with lrHPV infection [44]. Specifically, HPV6 and HPV11 cause 90 % of genital warts, over 95 % of recurrent respiratory papillomatosis cases, and ~10 % of early cervical lesions [45]. The infection can become more serious in immune-compromised individuals [44]. In our present survey, the incidence of HPV6 (4.01 %) infection was inconsistent with the results of Bruni et al. [25], who showed that HPV6 was most frequent among Americans (2.9 %) and was less frequent in Asian individuals (0.2 %), followed by HPV11 and HPV61.

Characterization of the prevalence of multiple HPV infections might be important for understanding its effects on cervical carcinogenesis. Herrero et al. [10] reported that women infected with HPV16 alone were at a similar or higher risk for cervical cancer than those infected with both HPV16 and another HPV type. Lee et al. [46] reported an association between infection with multiple HPV types and an increased risk of cervical cancer. In a recent study, Schmitt et al. [47] confirmed that co-infection would increase the duration of infection. Furthermore, patients with multiple high viral loads showed a 4- to 6-fold increased risk of cervical precancerous cytological lesions compared with patients with single high viral loads. In this present study, 434 hrHPV-positive samples (4.5 %) were multiple-infections. The incidence was in the same range (3.5–5.3 %) as was previously reported in China [37], but was higher than the global average (3.2 %) [25]. Furthermore, the rate of infection (14.19 %) was lower than reported for both domestic (25.8 %) [28] and international (20 %) [25] populations. The most common combinations of two types were HPV16 + HPV52 (26 cases) and HPV52 + HPV58 (14 cases), and the genotypes HPV52 and HPV58 were more likely to be involved in co-infections. Regarding region-specific surveillance, some geographical features were observed. For example, in Shanghai, a city with a large internal population, the situation was close to the world average regarding HPV prevalence, genotypic distribution, and multiple infections.

This present study confirmed the high overall incidence of HPV in China and strongly argues for the necessity of developing national population-based screening programs. However, the appropriate management of this HPV screening program for a large number of women with HPV-positive specimens and the absence of cytological evidence of cervical pre-cancer or cancer remains a major concern [48]. HPV genotyping could be an option to stratify the HPV-positive women. Furthermore, a stainable HPV detection and close follow-up program for hrHPV carrier women should be implemented. Thus, more cost-effective techniques, such as the Cervista™ HR HPV test, COBAS HPV test, and some other genotyping platforms, might be good alternatives for molecular detection of HPV [49].