An analysis of infections incidence of multiple human papillomavirus (HPV) rising in cervical and genital samples

Background : Human papillomavirus (HPV) is associated with cervical cancer and genital condyloma, which is mainly transmitted through sexual contact.Cervical HPV infection in females and genital HPV infection in males can induce epithelial proliferation on both mucosal and cutaneous surfaces. HPV is divided into high-risk (HR) and low-risk (LR) types according to their oncogenic potential. The HR geneotypes are considered as etiological factors for invasive cervical cancer in females, and the LR geneotypes are correlated with hyperplastic lesions, including external genital warts, condyloma acuminata, and so on. The aim of this study was to investigate the prevalence of HPV infection and geneotype distribution among individuals in Xinjiang Province. Methods A total of 1094 patients the etiology and species with characteristic of cervical and genital warty surface which mainly come from CA in dermatology and STD outpatient service of People's Hospital of Xinjiang Uygur Autonomous Region.Using a method of real-time fluorescence quantitative PCR for the detection of human papilloma virus HPV 23 typing. Results The prevalence of HPV infection was 67.46%, the most common LR-HPV subtypes were HPV-6 (16.27%), HPV-11 (4.57%), HPV-42(1.19%) and HPV-43(1.19%), and HR-HPV subtypes were HPV-16 (1.65%) and HPV-58(0.91%). The prevalence of HPV infection with single subtype and multiple subtypes was 32.91% and 34.55%, respectively. Among the females infected with a single HPV subtype, 26.11% were infected with a HR-HPV subtype. Among the females infected with multiple HPV subtypes, 18.52% were infected with multiple HR-HR HPV subtypes. The prevalence and subtype distribution of HPV infection showedage differences ( P =0.012), and

Conclusion The prevalence of multiple infection was higher than singleinfection, and the prevalence varied significantly with age while had little association with race and gender.

Background
As a small double-stranded DNA virus, human papillomavirus (HPV) can lead to epithelial proliferation on both mucosal and cutaneous surfaces and is mainly transmitted through sexual contact. Approximately 75% of sexually active adults have been infected with HPV in their lifetime, and 54% of these infections are cleared within two years [1] . However, a small portion persist or progress to preneoplastic lesions and even to cancer [2] . Approximately 5% of all cancers are attributable to HPV infection around the world. More than 200 HPV subtypes have been identified, and 40 subtypes can infect the ano-genital region and cause anal cancer with persistent infection among them [3] . In addition, HPV infection is an acknowledged cause of cervical cancer [4][5] . HPV is divided into high-risk (HR) and low-risk (LR) types according to their oncogenic potential [6] . The HR subtypes, such as HPV-16,-18,-31,-33,-35 and − 82, infect human epithelial cells and are considered as etiological factors of invasive cervical cancer in females [7][8] , and HPV-16 and HPV-18 induce several cancers of the anogenital tract in males, including approximately 50% of penile cancers [9] . The LR subtypes, such as HPV- 6, -11, -42 and − 81, have less oncogenic risk and are associated with hyperplastic lesions, including external genital warts, condyloma acuminata, and so on [10][11] . However, some studies showed that infection with multiple HR-HPV and LR-HPV subtypes occurred in cervical and vulvar specimens with intraepithelial lesions [12][13] , and there were occasional reports of the presence of HR-HPV subtypes in vulvar specimens diagnosed as condyloma acuminatum [14] , and LR-HPV subtypes in highgrade cervical lesions, mainly HPV-6 and HPV-11, cause the majority of anogenital warts [15] .
As one of the most widespread sexually transmitted diseases induced by HPV [16][17] , condyloma acuminatum (CA) represents a momentous HPV disease burden around the world and brings about substantial healthcare costs. LU et al.
reported that among 3288 CA patients with HPV infection, 61.98% were infected with a single HPV subtype, and 38.02% were infected with multiple HPV subtypes [18] . There was an increased risk of anal cancer or cervical cancer for CA patients since they were more likely to acquire a HR-HPV subtype, such as 16, 18, 31 and 45 [19] , and these subtypes were closely asociated with cervical cancers.
Wentzensen et al. aslo reported that most of invasive cervical cancer was correlated with different HPV subtypes [20] . However, the role of multiple HPV genotypes in females with cervical and genital infection has been ignored in most of reported studies, there are limited estimates for the prevalence of multiple HPV genotypes.
And in the present study, there are only several reports associated with the epidemiological characteristics of HPV infection in Xinjiang of China, and most of them focus on individuals with HR-HPV infection rather than individuals with LR-HPV or multiple infection. The prevalence and genotype distribution of HPV infection vary substantially with respect to certain factors, such as age, region, and so on [21] . In this study, we investigated the prevalence of HPV infection and geneotype distribution in females in Xinjiang.

Study population
This was a hospital-based study, which was permitted by the Ethical Committee of   (Table 1).   (Fig. 1A). The five most prevalent HPV subtypes were HPV-6, -11, -16, -42 and − 43 in Han, and HPV-6, -11, -53, -16 and − 58 in enthnic minorities (Fig. 1B). Among males, 52.49% were infected with a single HPV subtype and 47.51% with multiple HPV subtypes. Among females, 42.60% were infected with a single HPV subtype and 57.40% with multiple HPV subtypes. Among Han, 48.15% were infected with a single HPV subtype and 51.85% with multiple HPV subtypes, and 52.14% were infected with a single HPV subtype and 47.86% were infected with multiple HPV subtypes (Table 3).

Discussion
Investigations on the prevalence and subtype distribution of HPV infection in Xinjiang are seldom, especially in individuals infected with multiple HPV subtypes.
CA represents a momentous HPV disease burden around the world, which is associated with anal cancer, cervical cancer, penile cancer, vulva cancerand other genital cancers [22] . The samples in our study were mainly from patients with CA.
Many investigations have demonstrated that HPV infection is more widespread than expected, particularly in individuals infected with multiple HPV subtypes. The prevalence and genotype distribution of HPV infection are significantly different in different regions. Investigating these differences will be helpful for the prevention and treatment of HPV infection and development of HPV vaccine.
In this study, we investigated the prevalence and subtype distribution of HPV infection in cervical and genital samples in Xinjiang. The prevalence of HPV infection was 67.46%. Among them, 36.04% were infected with a single low-risk single subtype, 12.74% with a single high-risk single subtype, and 51.22% with multiple subtypes. These results showed thatthe prevalence of HPV infection with multiple subtypes was higher than that with a single subtype, which was consistent with previous studies [23] . It has been reported that HPV infection with multiple subtypes has greatly increased from 4-15.7% during the past two decades. Lee et al. [24] demonstrated that the risk of cervical cancer induced by HPV infection with multiple subtypes was higher than that induced by HPV infection with a single subtype. Ho et al. [25] believed that HPV infection with multiple subtype can induce persistent infection to a greater extent, while persistent infection is more likely to induce cervical cancer.
The distribution of HPV subtypes also exhibited regional differences. Recent studies have showed that the HR subtypes, including HPV-16, -18, -35, -45, -58 and − 59, were closely associated with cervical cancer, and the LR types, including HPV-6 and − 11, were main cause of genital condynoma [26][27] . In our study, the most common HPV subtypes were HPV-6,-11,-16,-42,-43 and − 58 in Xinjiang, which demonstrated a different genotype distribution compared with other regions. Certainly, this study was not a random sampling investigation based on the entire population in Xinjiang, which was a main limitation. Studies show that CA patients have increased risk of genital cancer except for cervical cancer in females [28] , and males infected by HPV were at risk of genital warts [29] . In this study, there were no differences in the prevalence and genotype distribution of HPV infection between Han and other ethnicities in Xinjiang. However, the differences were found among different ethnic groups in Yunnan Province [30] ,it was perhaps because Yunnan Province had more diversified nationalities than Xinjiang where ethnics were mainly Uygur.
Additionally, the distribution of HPV subtypes also exhibited age-related differences.
The peak prevalence of HPV infection was observed in the age group of 20-29 years, followed by the age group of 30-39 and 40-49 years in our study. Previous investigations have shown that high HPV prevalence was observed in the age group of below 20 years in Europe and the United States [31] , and in the age group of 30-44 years in India [32] , while in the age group of 40-49 yearsin China [33] which was possibly associated with relatively weak immunity in the elderly. In conclusion, HPV-6, HPV-11,HPV-16, HPV-43, HPV-42 and HPV-58 were the primary subtypes in females with HPV infection in Xinjiang, the prevalence of multiple infection was higher than singleinfection, and the prevalence varied significantly with age while had little association with race and gender. years old from their parents or guardians in this study.

Consent for publication
Informed consent was obtained from all individual participants included in the study, and once accepted, we all can consent for publication.

Availability of data and materials
All relevant data are within the paper. The data underlying this study are available and researchers may submit data requests to the the corresponding author on reasonable request.

Competing Interests
The authors declare that they have no competing interests.