Have you ever heard of Human Papillomavirus (HPV) vaccine? The awareness of HPV vaccine for college students in China based on meta-analysis

ABSTRACT

Objective: To evaluate the awareness of College Students (CSs) of HPV vaccine in China and provide evidence-based recommendations for HPV vaccine’s publicity and promotion.

Methods: Web of Science, PubMed, Science of Direct, EBSCO, China National Knowledge Infrastructure and Wanfang Data were searched. A random effects meta-analysis was conducted to determine pooled estimates of Awareness Rate (AR) for HPV vaccine.

Results: Of the 36 studies included, the estimated AR of HPV vaccine was 40.27% (95% CI: 30.86%, 50.06%) among Chinese CSs. The AR of HPV vaccine was stratified by factors as gender, major, area, city, survey time, and sampling method of the study. The pooled AR of HPV vaccine among CSs was as follows: 44.17% (95% CI: 31.65%, 57.09%) and 31.93% (95% CI: 13.25%, 54.30%) for females and males; 44.47% (95% CI: 29.90%, 59.55%) and 12.02% (95% CI: 7.69%, 17.15%) for medical-related and nonmedical majors; 44.47% (95% CI: 28.71–60.82%) and 41.16% (95% CI: 26.48–56.64%) for Eastern and Midwestern region; 48.86% (95% CI: 30.63–67.25%) and 33.19% (95% CI: 22.27–45.12%) for first-tier and second- and third-tier city; 29.67 (95% CI: 11.44–52.16%) and 38.81 (95% CI: 27.14–51.21%) for AR before and after HPV vaccine entered in China; 51.51% (95% CI: 32.21%, 70.53%) and 26.21% (95% CI: 17.41%, 36.10%) for nonrandom and random sampling.

Conclusion: This review indicates that awareness of HPV vaccine among CSs remains relatively low in China compared with European countries. Our findings may provide useful information to better understand the HPV vaccine awareness status among Chinese CSs.

KEYWORDS:

• Human papillomavirus vaccine
• HPV vaccine
• awareness rate
• meta-analysis

Introduction

Cervical cancer is one of the most common malignant tumors for women worldwide. The incidence and mortality rate of this cancer in China is the first place in female reproductive system malignant tumors, and ranks second in women aged 15–44 years old.¹ In 2018, China was the country with the highest estimated number of 106,000 incident cases of cervical cancer and the number of 48,000 deaths.² The continuous infection of High-Risk Human Papillomavirus (HR-HPV) was considered to have played an important role in the occurrence and development of cervical cancer. The World Health Organization (WHO) has recognized the importance of cervical cancer and other Human Papillomavirus (HPV) related diseases as global public health problems, and reiterated the recommendation that HPV vaccine should be included in the National Immunization Program (NIP).³

Since 2006, three types of HPV vaccines have been approved worldwide to effectively prevent abnormality caused by persistent HR-HPV infection, namely Cervarix® 4, Gardasil® 4 and Gardasil® 9. Therefore, WHO’s position paper on HPV vaccines suggested that the introduction of HPV vaccine should be part of the strategy to prevent cervical cancer and other HPV-related diseases, and HPV vaccination should be carried out in primary target population (women aged 9–14 years) and secondary target population (women aged 15 years and above).³ At present, HPV vaccine remains a non-immunization program vaccine in China, which follows the principle of informed, voluntary and self-funded vaccination. It is officially defined as the supplement to the NIP vaccine. In response to WHO’s global goal of eliminating cervical cancer, it is urgent to enhance people’s knowledge and awareness of HPV vaccine to improve its public coverage. The successful control and prevention of cervical cancer largely depend on the public’s basic cognition of vaccination.

College Students (CSs), generally between 18 and 25 years old, live a more independent and freer lifestyle and are highly susceptible to HPV infection because most of the first sexual behaviors occurred during college years.⁴ Meanwhile, this age group is highly coinciding with the recommended vaccination age of HPV vaccine in China. In addition, at the childbearing age, CSs will also affect the next generation based on their thoughts and attitudes to HPV vaccine.⁵ Hence, assessing the awareness and understanding of HPV vaccination among CSs is worthy of attention, which is conducive to successful reduction of potential infection of HPV and control of cervical cancer.

Since the HPV vaccine came into being, numerous papers related to knowledge, attitude, and practice tendencies on HPV vaccination in Chinese CSs have been published.^6–11 Most of them were cross-sectional designs in one region,^7–11 one organization,¹¹ or among females.^6–9 Besides, there have been previous systematic reviews and meta-analyses evaluating HPV awareness and knowledge in China. Meta-analyses conducted by Zhang¹² and Yu¹³ concluded that HPV vaccine awareness among Chinese population was low between 2006 and 2015, with AR of 15.95% (95% CI: 12.87%, 19.29%) and 17.13% (95% CI: 14.04%, 20.46%) respectively. However, both studies were performed before the vaccine entered mainland China and reviews of evaluating HPV vaccine awareness among CSs population after that are insufficient. The idea of this study aims to delve into the level of awareness toward HPV vaccine among CSs across the nation.

Materials and methods

Search strategy

A systematic literature search was conducted in the Web of Science, PubMed®, Science of Direct, EBSCO®, China National Knowledge Infrastructure (CNKI®) and Wanfang Data. The search was limited to original articles in English and Chinese, without limitations regarding the year of publication. The last search date was October 8, 2020. The research protocol was registered in the PROSPERO international prospective register of systematic reviews (CRD42020213364).

The search strategy (see Appendix A) consists of combined terms of HPV, human papillomavirus, vaccine, and vaccination. One author (G.Y.) screened all titles and abstracts. Full-text articles were obtained if the abstract fulfills the inclusion and exclusion criteria. Consequently, all full-text articles were reviewed by two researchers independently (G.Y. and Y.Z., or G.Y. and C.C.). Any disagreements between the researchers were resolved by discussion. In case of multiple articles published on the same study population, only the publication with the most relevant results was further evaluated. Additional studies including gray literature were identified by checking reference lists and by Google Scholar retrieval. Also, the reference lists of all the included studies were checked.

Selection criteria

For this review, studies reporting sample size and Awareness Rate (AR), or providing the data that could calculate the AR indirectly among CSs were eligible for inclusion in the meta-analysis. The selection criteria are shown in Table 1.

Table 1. Selection criteria

Inclusion criteria	1. Study design must be cross-sectional or observational;
	2. Study object must be or include Chinese college students;
	3. Study must report the sample size and AR, or provide the data that can calculate the AR;
	4. Literature type must be original article.
Exclusion criteria	1. Study unrelated to the awareness or knowledge about HPV vaccine, such as adverse reactions, clinical trials and so on;
	2. Study involving human intervention measures, such as propaganda and education during the vaccination process;
	4. Raw data that cannot be extracted or converted;
	5. Writing language is not Chinese or English.

After strict screening, 36 articles were selected ultimately, including 26 in Chinese and 10 in English. Although most of the included studies were published in China, the quality of all the chosen literature could be considered as adequate to considerable quality, because academic articles published in China are still subject to peer-review and academic publication process. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) flow chart of literature retrieval could be illustrated in Figure 1.

Figure 1. MOOSE flow chart of the review

*Results of retrieval for each database were as follows: Web of Science: 9,030; PubMed: 5,727; ScienceDirect: 2,373; EBSCO: 21,028; CNKI: 12,238; Wanfang: 7,632.

Data extraction

The following general information was extracted from the included articles by one author (G.Y.): first author, collection period, area, region, study participants and setting (i.e., source of participants), sample size, sampling method, and quality level. For the literature that the AR was not directly given, two researchers (C.C. and H.R.) independently calculated it, and those with consistent results were applied. If the results were inconsistent, the third evaluator (B.G.) will intervene, and the final result will be available after discussion depending on consensus. If necessary, we also contacted corresponding authors for additional information to ensure accuracy in the calculation.

We found that there were mainly two ways to ask questions about awareness of HPV vaccine in the included studies: (1) Do you know the HPV vaccine? (2) Have you ever heard of HPV vaccine? Accordingly, the answers to the above questions were YES, NO, and UNCLEAR respectively. If the respondent in the study answered YES, we considered he or she knew about HPV vaccine. If the respondent answered NO or UNCLEAR, we did not consider he or she knew about the HPV vaccine. The AR of HPV vaccine was extracted directly from the literature if it is reported in the study. Otherwise, the AR of HPV vaccine was calculated by dividing the number of people who were aware of the HPV vaccine with the overall sample size.

Statistical analysis

Data were analyzed from October to November 2020 by four reviewers (G.Y., C.C., H.R., and B.G.) in accordance with MOOSE and A MeaSurement Tool to Assess systematic Reviews (AMSTAR) reporting guidelines.¹⁴ STATA (Version 15.1, Stata Corp, Texas, USA) software was used for meta-analysis. The score method was used for the Freeman-Tukey double arcsine transformation of the 95% confidence interval on the pooled estimates.¹⁵ Meanwhile, sources of heterogeneity (i.e., variation in the research results) were explored using subgroup analyses. I² statistic was used to describe the heterogeneity across the studies. Conventionally, when I² ≤ 50%, a fixed effects model was employed; when I² > 50%, a random effects model was used. Besides, potential publication bias was explored using funnel plots and Egger’s test.¹⁶ Sensitivity analysis was performed to evaluate the robustness of the findings. Two-sided p< .05 indicated statistical significance.

Methodological quality appraisal

Evaluation of the methodological quality was independently performed by two reviewers (M.Z. and C.C.), and inconsistencies were determined by the third reviewer (G.Y.) after discussion. The methodological quality of the studies included in this review was assessed using an 11-item checklist which was recommended by Agency for Healthcare Research and Quality (AHRQ) for cross-sectional study.¹⁷ An item would be scored 0 if it was answered NO or UNCLEAR; if it was answered YES, then the item scored 1. Article quality was assessed as follows: 0 to 3 points were defined as low quality, 4 to 7 points as moderate quality, and 8 to 11 points as high quality.

Results

Included literature feature

A total of 36 articles were included based on the inclusion and exclusion criteria. The total number of samples was 117,686. The sample size varied widely in different studies, ranging from 105 to 11,236. There were 12 articles on CSs, 6 on female CSs, 1 on male CSs, 2 on medical CSs, and 2 on non-medical CSs. Seventeen researches were conducted in Eastern region, five in Central region, eight in Western region, and three in whole nation. Geographic distribution feature of included studies is illustrated in Figure 2.

Figure 2. Geographic distribution feature of included studies

The characteristics of included articles are provided in Table 2 in detail. Most of the quality of the included articles attained medium scores, ranging from 3 to 8 points based on AHRQ scale, with an average of 6.47. The main loss items of quality evaluation are as follows: (1) Not describe any assessments undertaken for quality assurance purposes; (2) Not describe how confounding was assessed and/or controlled; (3) Not explain how missing data were handled in the analysis; (4) Not clear in the follow-up data.

Table 2. Research characteristics of included studies (n = 36)

No.	First author	Collection period	Area	Region	Study participants and setting	Simple size	Sampling method	Quality level
1	Chang, IJ^Citation6	Aug. 2011–Nov. 2011	Nationwide	Nationwide	1146 employed women and 557 female undergraduate CSs	557	NR	Moderate
2	Wang, HH^Citation7	NR	Taiwan	East	150 female CSs, Taiwan	150	Convenience sampling	Moderate
3	Gu, C^Citation8	Jun. 2012	Changsha, Hunan	Central	117 female undergraduate CSs, Changsha, Hunan province	117	Convenience sampling	High
4	Leung, JTC^Citation9	NR	Hong Kong	East	195 female CSs, Hong Kong	195	Convenience sampling	Moderate
5	Zou, HC^Citation10	Jan. 2013	Jinan, Shandong	East	375 CSs, Jinan, Shandong province	351	NR	Moderate
6	Liu, YN^Citation11	Sept. 2018–Dec. 2018	Beijing	East	884 CSs in Peking University, Beijing	827	NR	Moderate
7	Li, M^Citation18	Dec. 2012–Mar. 2013	Beijing	East	383 parents for junior high school students and 409 CSs in general universities, Beijing	409	Convenience sampling	Moderate
8	Jiang, Y^Citation19	Jan. 2018	Chengdu, Sichuan	West	300 CSs in three comprehensive universities, Chengdu, Sichuan province	294	Convenience sampling	Moderate
9	Huang, H^Citation20	Nov. 2011–Dec. 2011	Chengdu, Sichuan	West	472 non-medical CSs, Chengdu, Sichuan province	470	Multistage random sampling	Moderate
10	Zhu, YR^Citation21	Aug. 2016	Changsha, Hunan	Central	325 CSs in medical university and general university, Changsha, Hunan province	309	Stratified cluster sampling	Moderate
11	Zhang, JR^Citation22	NR	Xi’an, Shanxi	West	310 CSs in Xi’an Jiaotong University, Xi’an, Shanxi province	252	Simple random sampling	Low
12	Xu, J^Citation23	NR	Xi’an, Shanxi	West	365 CSs in Xi’an International University, Xi’an, Shanxi province	353	Stratified cluster sampling	Moderate
13	Jia, XH^Citation24	May 2018–Aug. 2018	Ganzhou, Jiangxi	Central	2180 female CSs in Ganzhou, Jiangxi province	2091	Simple random sampling	Moderate
14	Zhao, H^Citation25	Oct. 2017–Dec. 2017	NR	NR	600 vocational female CSs	583	Stratified sampling	Moderate
15	Zhang, J^Citation26	Oct. 2017–Dec. 2017	Guangzhou, Guangdong	East	1300 CSs in five universities, Guangzhou, Guangdong province	1244	Cluster sampling	Moderate
16	Li, M^Citation27	NR	Liuzhou, Guangxi	West	583 CSs, Liuzhou, Guangxi province	583	NR	Low
17	Wei, ZS^Citation28	NR	Guangzhou, Guangdong	East	600 undergraduate CSs, Guangzhou, Guangdong province	579	Convenience sampling	Moderate
18	Yu, X^Citation29	Nov. 2018–Feb. 2019	Nanchang, Jiangxi	Central	1000 CSs in five universities, Nanchang, Jiangxi province	987	Convenience sampling	High
19	Liu, KY^Citation30	NR	Yinchuan, Ningxia	West	309 CSs in nursing major, Yinchuan, Ningxia province	309	Convenience sampling	Low
20	Yan, TF^Citation31	Sep. 2019–Oct. 2019	Urumqi, Xinjiang	West	500 female CSs in medical college, Urumqi, Xinjiang province	485	Cluster sampling	Moderate
21	Liu, YH^Citation32	NR	NR	NR	805 female CSs	805	Convenience sampling	Moderate
22	Song, QQ^Citation33	Feb. 2017–Apr. 2017	Xiamen, Fujian	East	1760 CSs in six universities, Xiamen, Fujian province	1760	Stratified sampling	Moderate
23	Li, YF^Citation34	Mar. 2018–Jun. 2018	Xiamen, Fujian	East	1342 male CSs in five universities, Xiamen, Fujian province	1209	Convenience sampling	High
24	Lu, J^Citation35	Sept. 2014–Mar. 2015	Shanghai	East	878 CSs in three universities, Shanghai	810	Stratified cluster sampling	Moderate
25	Pan, D^Citation36	Feb. 2017–Mar. 2018	Taizhou, Zhejiang	East	86 civil servants, 811 college students and 220 medical staff, Taizhou, Zhejiang province	811	Stratified cluster sampling	Moderate
26	Pan, D^Citation37	Jan. 2018–Aug. 2019	Taizhou, Zhejiang	East	11236 female CSs, Taizhou, Zhejiang province	11236	Cluster sampling	Moderate
27	Yang, J^Citation38	Oct. 2015	Xi’an, Shanxi	West	2131 female CSs in six nonmedical universities, Xi’an, Shanxi province	2096	Cluster sampling	Moderate
28	Ma, D^Citation39	NR	NR	NR	260 medical CSs	258	NR	Moderate
29	Jiang, SF^Citation40	NR	Zhejiang	East	105 CSs, Ningbo and Taizhou, Zhejiang province	105	Convenience sampling	Low
30	Zeng, XM^Citation41	NR	Guangzhou, Guangdong	East	2574 undergraduate CSs in Sun Yat sen University, Guangzhou, Guangdong province	2004	NR	Moderate
31	Fu, SL^Citation42	May 2009–May 2012	Nationwide	Nationwide	11235 female residents, 758 medical staff, 762 civil servants, 2198 parents of junior high school students and 3015 CSs	3015	Convenience sampling	High
32	Wang, SM^Citation43	Nov. 2011–May 2012	Nationwide	Nationwide	3497 CSs	3295	Stratified sampling	Moderate
33	Liu, A^Citation44	May 2013–Dec. 2013	Hong Kong	East	1022 undergraduate medical CSs, Hong Kong	781	NR	Moderate
34	Chiang, VCL^Citation45	Apr. 2015–Sept. 2015	Hong Kong	East	520 CSs, Hong Kong	437	Convenience sampling	High
35	Choi, EPH^Citation46	Jul. 2014–Nov. 2015	Hong Kong	East	888 CSs in four major universities, Hong Kong	888	Convenience sampling	Moderate
36	Ouyang, LC^Citation47	Oct. 2018–Dec. 2019	Wuhan, Hubei	Central	364 female medical CSs in Jianghan university, Wuhan, Hubei province	364	Convenience sampling	Moderate

NR: Not Reported.

Full combined effect value

A heterogeneity test was carried out on 36 included articles, and the results reflected that there is a large heterogeneity among the researches, with I² statistic = 99.74% and p < .001. Hence, random effects model was conducted in the meta-analysis. The pooled AR in 36 articles was 40.27% (95% CI: 30.86%, 50.06%) and forest plot of meta-analysis is shown in Figure 3.

Figure 3. Forest plot of meta-analysis among 36 studies, random effects model

Subgroup analysis

In this review, subgroup analysis was employed to explore the heterogeneity by stratification as follows: (1) gender, (2) major, (3) area, (4) city, (5) survey time, and (6) sampling method. Subgroup analysis revealed a marked disparity in AR among CSs in China regarding gender, major, city, survey time and sampling method. The results in subgroup analysis are shown in Table 3.

Table 3. Subgroup meta-analysis of AR among CSs in China

Group		Reference	AR(%)	95% CI	I^2(%)	P
Total		36	40.27	30.86–50.06	99.74	.00
Gender	Male	10	31.93	13.25–54.30	99.59	.00
	Female	20	44.17	31.65–57.09	99.67	.00
Major	Medical-related	8	44.47	29.90–59.55	98.85	.00
	Non-medical	6	12.02	7.69–17.15	97.22	.00
Area	Eastern	17	44.47	28.71–60.82	99.81	.00
	Midwestern	13	41.16	26.48–56.64	99.51	.00
City	First-tier city	19	48.86	30.63–67.25	99.77	.00
	Second and third-tier city	11	33.19	22.27–45.12	99.55	.00
Time	Before 2016	12	29.67	11.44–52.16	99.85	.00
	After 2016	13	38.81	27.14–51.21	99.64	.00
Method	Random sampling	14	26.21	17.41–36.10	99.60	.00
	Nonrandom sampling	15	51.51	32.21–70.53	99.73	.00

Sensitivity analysis

According to the results of literature quality evaluation, the meta-analysis was conducted again after 4 articles^11,27,30,40 with relatively low quality were excluded. The results showed that the combined value of AR in the remaining 32 articles was 37.25% (95% CI: 27.68–47.31%), which was similar to the original result by 40.29% (95% CI: 30.86–50.06%), and the combined effect value after elimination basically showed little distinction. The results of sensitivity analysis appeared reliable and robust in this meta-analysis.

Publication bias analysis

Publication bias in studies was assessed in this review. The funnel plot is shown in Figure 4 by Begg’s test. We can clearly see that the distribution was dispersed, with most of researches in the underside of the funnel plot. Meanwhile, the results calculated by Egger linear regression (p = .008) also indicated that there was a significant publication bias in the meta-analysis.

Figure 4. Begg’s funnel plot of 36 studies

r means effect size (i.e., awareness rate), s.e. means standard error of effect size r.

Discussion

What is Chinese college students’ awareness level toward HPV vaccine?

It is crucial to enhance the public’s awareness of HPV vaccine as an effort to expand the scope of immunization because awareness is an essential step in vaccination. This study demonstrated an estimated value of the AR of HPV vaccine among CSs in China. The results showed that 40.27% (95% CI: 30.86%, 50.06%) of Chinese CSs had heard of HPV vaccine, which is lower than those in Italy (69.9%),⁴⁸ but higher than those in India (36.8%),⁴⁹ Turkey (26.6%)⁵⁰ and Thailand (25.3%).⁵¹ It is reasonable to infer that there may be a higher percentage of general population ignorant of the vaccine, given that over half of the highly educated group does not know about HPV vaccine. Apparently, if the target group is unaware of HPV vaccine’s existence, the vaccination is far from a reality. The awareness of HPV vaccine among CSs group in China, compared with other developed countries,^52–54 is still weak. This indicates that delivery of HPV vaccination education to CSs in China needs to be reevaluated and valued by authorities. Besides, the literature review showed that there were few studies related to male CSs and North-eastern regions on the awareness of HPV vaccine, which indicates that the aforementioned areas should be prioritized in future research.

Gender

In this review, we found that most of the studies on the knowledge, attitude, and practice of HPV vaccine were conducted among women, and few involved men. And AR of female CSs (44.17%, 95% CI: 31.65%, 57.09%) was higher than male group (31.93%, 95% CI: 13.25%, 54.30%). There is a high probability that HPV vaccine is generally regarded as cervical cancer vaccine by the public in China, which seems to have nothing to do with men. In fact, boys can play an important role in directing their partners or elders to get vaccinated, especially in the CSs group. Meanwhile, the knowledge of HPV vaccination in male group can improve personal hygiene and habits to a certain extent and indirectly reduce HPV infection rate in females, given the truth that men are the primary transmission vector of HPV to women.⁴⁶ Besides, HPV is responsible for malignancies in men too, including malignant tumors of the anus, penis, oral cavity, and oropharynx. What needed to be clear is that HPV vaccination is also beneficial to boys. Many countries worldwide (US, UK, Australia, etc.) have included boys in National Vaccination Programs to eliminate HPV-related diseases and save lives. Although concurrent efforts to vaccinate both males and females could provide a more effective way to reduce the prevalence of HPV infections in the population,⁴⁶ male groups have not yet been included in the target population for HPV vaccination in China, owing to production capacity of the vaccine and vaccination regulations. Nevertheless, it is still necessary for men to promote their awareness of this vaccine because only mutual cognition of this virus and its vaccination could lead to the decrease in the incidence of HPV-related STIs (Sexually Transmitted Infections) and cervical cancer.

Major

A total of 36 studies concerning Chinese CSs showed that there was a big gap of AR between medical-related majors (44.47%, 95% CI, 29.90%, 59.55%) and non-medical related majors (12.02%, 95% CI, 7.69%, 17.15%). This is consistent with the results of a Turkish study.⁵⁵ After all, medical-related majors refer to clinical medicine, nursing, medical imaging, pharmacy, and health management. Students of these majors will learn more about professional knowledge on campus, who act as primary information popularizers and play a critical role in wide spreading of awareness among citizens. Thus, it is reasonable to reckon it urgent, because more than half of the medical-related CSs do not know this kind of vaccine. The relevant knowledge and assessment of HPV could be added in the compulsory or optional courses for medical-related students to increase their cognition of HPV and vaccination. It is helpful to better convey vaccination knowledge to the general population in their future practice.

Region

Two categories, namely area and city, were used to discuss the influence of region on HPV awareness in this study. AR in Eastern region (44.47%, 95% CI: 28.71–60.82%) was slightly higher than that of Midwestern region (41.16%, 95% CI: 26.48–56.64%). At the same time, according to the sample cities included in the literature, two types of cities (first-tier and second- and third-tier cities) were categorized based on political status, economic strength, city size, and regional influence. AR in second- and third-tier cities (33.19%, 95% CI: 22.27–45.12%) was lower than that in first-tier cities (48.86%, 95% CI: 30.63–67.25%). It is obvious that the classification results from cities showed more disparities than areas. The reason for this variation is not entirely clear but it is indicative of gaps in state or municipal policies and strategies regarding publicity of HPV immunization-related knowledge, since the central administration has no compulsory regulations in terms of promotion and publicity of the non-immunization program vaccine. Compared with second-and third-tier cities, residents in first-tier cities have both a relatively higher educational and health consciousness level, and are willing to accept new things. This may account for the discrepancy in AR of HPV vaccine among different types of cities.

Time

It has been demonstrated that immunization awareness has been improved since HPV vaccine came into mainland China (Cervarix® 4 and Gardasil® 4 were approved and licensed in July 2016 and May 2017, and Gardasil® 9 in April 2018), yet CSs in China still have limited knowledge about the HPV vaccination. After all, HPV vaccine is still a new thing in China compared with developed countries. The result seems to be similar in this study. Our findings indicated that AR of CSs regarding HPV vaccine was 29.67% (95% CI: 11.44%, 52.16%) before 2016, and 38.81% (95% CI: 27.14–51.21%) after 2016. Although the awareness of HPV vaccine of CSs has increased after its access to the market, it is still far from sufficient compared with the countries that have incorporated the vaccine in NIP.^56–58 This may be owing to insufficient publicity and avoidance of mentioning reproductive organs in traditional Chinese culture. It should be noted that there are still nearly 60% of Chinese CSs who don’t know about HPV vaccine at all after its entry into mainland market. This may reflect the lag of policy propaganda to some extent.

Sampling method

Nonrandom sampling, such as convenience sampling, is more convenient and flexible and favored by researchers in cross-sectional study. Yet we found that there was a significant variance between random (26.21%, 95% CI: 17.41%, 36.10%) and nonrandom (51.51%, 95% CI: 32.21%, 70.53%) sampling about AR of HPV vaccine in this study. As we know, there may be some shortcomings about nonrandom sampling such as small sample size and insufficient representativeness, which may lead to greater heterogeneity in the combined results of meta-analysis even if subgroup analysis is carried out. Meanwhile, nonrandom sampling may increase the positive rate due to the subjectivity of sample selection. This enlightens us to choose random sampling method as far as possible in future observational research, so as to ensure the scientific and random selection process of research objects.

Why have so few Chinese college students heard of the HPV vaccine?

In China, inoculation is an essential part of the Basic Public Health Services (BPHS) of the country and is subject to annual evaluation by the local health administration, such as vaccination status and archives establishment. According to Vaccine Administration Act issued in 2019, vaccines are generally divided into two types, that is, the immunization program vaccine (i.e., vaccinated obligatorily by the government for free, included in NIP) and the non-immunization program vaccine (i.e., vaccinated voluntarily at one’s own expense). However, only the vaccines included in NIP were written into evaluation plan. Therefore, the coverage of non-immunization program vaccines such as HPV vaccine is not regulated and required by the official sectors. Naturally, this leads to divergent policies regarding HPV vaccination in different cities and regions in mainland China. The publicity and promotion of this kind of vaccine gradually become the independent behavior of vaccination institutions for extra service income. Also, residents can only understand the knowledge and vaccination procedures of HPV vaccine through self-cognition or limited publicity channels according to their own needs. There may be obstacles in the equalization of delivery about public vaccination knowledge without administrative intervention. This calls for stricter enforcement of legislation aimed at boosting awareness of HPV vaccination, as well as frequent evaluation of HPV immunization programs.

Besides, in terms of health education for CSs including essential infectious disease education, the central education authority has not enacted specific rules on the curriculum of training for CSs, such as inclusion of health teaching and other related lessons. This also partly explains why most CSs know HPV vaccine online and on TV, rather than in classroom.⁴⁵ In order to better understand the circumstance of vaccination knowledge imparted to CSs on campus, a cross-sectional survey (by G. Yin, Y. Zhang, C. Chen, M. Zhang, unpublished work) was conducted in Wuhan University and Hubei University in November 2020. The results showed that among 321 valid questionnaires (111 males and 210 females), 82.55% CSs reported that the school did not set up health education-related courses. 86.60% CSs have not taken health education-related courses and 92.83% CSs have never participated in activities relevant to HPV vaccination on campus such as lecture, exhibition and roadshow. Key items and frequencies of the questionnaire are shown in Table 4. The survey revealed that the publicity and promotion of HPV vaccination in Chinese universities were inadequate and incomplete. Chinese CSs have a significant demand for HPV-related knowledge. Deficiencies in campus education regarding the delivery of HPV vaccination knowledge for common CSs were still prominent. Therefore, it is urgent to augment public awareness of HPV vaccines to boost its coverage.

Table 4. Health education status of HPV vaccine in Chinese CSs on campus

Item	Yes (%)	No (%)
Does your school offer health-related courses?	56 (17.45)	265 (82.55)
Have you ever chosen health-related courses?	43 (13.40)	278 (86.60)
Has your teacher taught you about HPV vaccine-related knowledge?	98 (30.53)	223 (69.47)
Have you talked about HPV vaccine with your friends?	112 (34.89)	209 (65.11)
Have you ever attended activities on campus related to HPV vaccine awareness?	23 (7.17)	298 (92.83)

Recommendations

In light of Knowledge-Attitude-Behavior theory, influence on individual’s health behavior is first through information reception, followed by the expectation of attitude change and subsequent desired behavior changes.⁵⁹ Therefore, sufficient knowledge acquisition for individuals is an essential component of the immunization process.

First, it is of great importance that the Chinese government should exert its leadership role and integrate various social resources by encouraging closer ties between key stakeholders,⁶⁰ including vaccine manufacturers, those in healthcare sector, and academia in order to incorporate HPV vaccine into NIP as soon as possible, or at least conduct inoculation in priority groups with the right age like CSs. This is consistent with the recommendations of The Plan for the Elimination of Cervical Cancer proposed by WHO.⁶¹ Meanwhile, some effective measures such as necessary legislation should be taken by the Central Health Administration and CDC to avoid information asymmetry in promotion and delivery of HPV vaccine between cities and regions which may lead to unfairness in BPHS.

Second, as the responsible agency for vaccination¹ of residents, immunization-related health knowledge could be disseminated by CDC, community health service centers and town hospitals, which are acceptable for citizens, particularly CSs. Possible ways are WeChat subscription, official Tiktok, and other online platforms. Besides, health officials and professionals are recommended to promote information quality construction to improve the standards of HPV immunization messages online, since high quality and audience-friendly online messages are important for the cognition and acceptance of HPV vaccine among the public.⁶²

Third, it is suggested that timely, active and targeted education is crucial to improve the awareness level of HPV vaccine among CSs on campus. Related studies indicated that educational interventions to increase HPV awareness and vaccination may help to boost vaccination rate.⁶³ Chang’s study found that a short period of educational intervention can significantly improve the public awareness of HPV vaccine. After one-hour health lecture education, the acceptability of HPV vaccine among college students can be increased from 73% to 82%.⁶ Therefore, targeted intervention measures such as health courses, lecture education, leaflets and posters could be actively taken to achieve the goal of primary prevention of cervical cancer on campus.

Conclusion

HPV vaccine was a proven method that could effectively prevent the infection of HR-HPV in humans. Cultivating knowledge and awareness among youngsters, especially CSs, may effectively enhance the uptake of HPV vaccine so as to minimize the incidence of HPV-related STIs and cervical cancer. This up-to-date meta-analysis reviews the basic awareness of CSs toward HPV vaccine, which may provide evidence-based suggestions for further promotion of the vaccination coverage. Our study reveals that Chinese CSs’ awareness of HPV vaccine remains suboptimal compared with that of European countries. In response to weak awareness, corresponding measures need to be properly proposed and implemented in a common effort by the health administration, vaccination institution and campus to increase HPV vaccination awareness in CSs.

Strengths and limitations

There have been previous systematic reviews and meta-analyses evaluating HPV awareness and knowledge in China of different population samples, but ours is the most up-to-date review that pays close attention to college students, the primary target group for HPV vaccine. However, there still are some limitations in the review. First, although strict selection and quality assessment were conducted in the included articles, heterogeneity among studies was high owing to the number of studies included and various study populations. Second, the articles included were cross-sectional studies, which inevitably have inherent shortcomings of cross-sectional design. Third, the search strategy excluded articles written in languages other than English and Chinese, whereby relevant results may have been missed. Fourth, although some of the included studies were published in Chinese peer-reviewed academic journals, this may still create some possible bias in the analysis.

Author contributions

G.Y. and M.Z. designed study. G.Y., Y.Z. and C.C. conducted the literature search and review. G.Y., C.C., H.R. and B.G. reviewed citations and extracted data. G.Y. and Y.Z. analysed the data. G.Y. and Y.Z. wrote and edited manuscript. M.Z. supervised review. All authors critically revised for important intellectual content.

Disclosure of potential conflicts of interest

The author declared no competing interests with respect to the research.

Acknowledgments

Thanks are due to Ms. Yuting Liao from Beijing Foreign Studies University for valuable discussion.

Additional information

Funding

This study was supported by Overseas Returnees Science Foundation of Heilongjiang [grant number: LC2011C41], and Sichuan Philosophy & Social Science Project [grant number: YF13-Y11]. The funding body has no role in the manuscript writing and publication.

Notes

1. According to the National Basic Public Health Services Standard in China, vaccine inoculation is a part of Basic Public Health Services (BPHS) item. Hence, vaccination institutions or vaccinations agency are generally regarded as health institutions with vaccination qualification, including local CDC, community health service centers and town hospitals. The vast majority of vaccination institutions are primary medical institutions, while large public hospitals generally do not undertake the responsibility of inoculation.

Appendix A.

Search strategy

The last search date was October 8, 2020.

1. Web of Science, WOS

Table

Search number	Results	Query
#3	9,030	#2 AND #1
#2	241,862	TI = (vaccine OR vaccination)
#1	45,953	TI = (HPV OR human papillomavirus)

2. PubMed

Query: (“vaccine”[Title] OR “vaccination”[Title]) AND (“HPV”[Title] OR “human papillomavirus”[Title])

Results: 5,727

3. Science of Direct, SOD

Query: Title: (HPV OR human papillomavirus) AND (vaccine OR vaccination)

Results: 2,373

4. EBSCO

Query: TI (HPV OR human papillomavirus) AND TI (vaccine OR vaccination)

Results: 21,028

5. China National Knowledge Infrastructure, CNKI

Query: (TI = ‘HPV’ OR TI = ‘human papillomavirus’ OR TI = ‘人乳头瘤病毒’) AND (TI = ‘疫苗’ OR TI = ‘接种’ OR TI = ‘免疫’ OR TI = ‘vaccine’ OR TI = ‘vaccination’)

Results: 12,238

6. Wanfang Data

Query: (题名:(HPV) OR 题名:(human papillomavirus) OR 题名:(人乳头瘤病毒)) AND (题名:(疫苗) OR 题名:(接种) OR 题名:(免疫) OR 题名:(vaccine) OR 题名:(vaccination))

Results: 7,632