A total of 967 female college students from two schools were surveyed between February and July 2020. Of these participants, 21 were excluded due to they had received HPV vaccination before the survey. In total, 946 eligible students were enrolled and then randomly divided into the control and the intervention group. More than half (56.2%, 532/946) of the enrolled students were in the intervention group and received online health education about HPV and HPV vaccines for seven days. Immediately after the intervention and one month later after the intervention, a total of 810 and 820 students completed the post-intervention questionnaire, respectively (Fig. 1).
Participants’ characteristics
The mean age of the participants was 18.99 years, and more than half (54.5%) majored in science. The majority of the participants were ethnic Han Chinese (93.0%). 75.5% had lived in urban areas for more than one year, and 69.6% of them had monthly living expenses between 1,000 and 2,000 Chinese Yuan (CNY). 35.7% of the students had parents with junior high school or below, 29.5% with senior high school, and 34.9% with a bachelor's degree or above. Furthermore, 79.0% of students had ever received sexual education or knowledge, and 35.1% of students reported having searched or consulted for HPV vaccines. The vast majority (98.2%) of the students had not had sex, and 84.8% were single. There was no statistically significant difference in general demographic characteristics between the intervention and control groups, except for receiving sexual education or knowledge before the survey (81.8% vs. 74.9%) (Table 1).
Table 1 Demographic characteristics of female college students
Variables
|
All, N (%)
|
Control group, n (%)
|
Intervention group, n (%)
|
p
|
Total participants
|
967 (100)
|
414 (43.8)
|
532 (56.2)
|
|
Research Site
|
|
|
|
|
Western
|
453 (46.8)
|
177 (42.8)
|
260 (48.9)
|
0.061
|
Central
|
514 (53.2)
|
237 (57.2)
|
272 (51.1)
|
|
Major
|
|
|
|
|
Liberal art
|
430 (44.5)
|
174 (42.0)
|
249 (46.8)
|
0.143
|
Science
|
537 (55.5)
|
240 (58.0)
|
283 (53.2)
|
|
Ethnic group
|
|
|
|
|
Han Chinese
|
899 (93.0)
|
390 (94.2)
|
490 (92.1)
|
0.209
|
Non-Han Chinese Minority
|
68 (7.0)
|
24 (5.8)
|
42 (7.9)
|
|
Permanent residence place (more than one year)
|
|
|
|
|
Urban
|
730 (75.5)
|
303 (73.2)
|
407 (76.5)
|
0.242
|
Rural
|
237 (24.5)
|
111 (26.8)
|
125 (23.5)
|
|
Education of parents
|
|
|
|
|
Junior high school or below
|
345 (35.7)
|
151 (36.5)
|
192 (36.1)
|
0.976
|
Senior high school
|
285 (29.5)
|
121 (29.2)
|
159 (29.9)
|
|
College and above
|
337 (34.9)
|
142 (34.3)
|
181 (34.0)
|
|
Living expenses per month (CNY*)
|
|
|
|
|
<1,000
|
201 (20.8)
|
84 (20.3)
|
116 (21.8)
|
0.851
|
1,000~2,000
|
674 (69.7)
|
293 (70.8)
|
369 (69.4)
|
|
>2,000
|
92 (9.5)
|
37 (8.9)
|
47 (8.8)
|
|
Received sexual education
|
|
|
|
|
Yes
|
764 (79.0)
|
310 (74.9)
|
435 (81.8)
|
0.010
|
No
|
203 (21.0)
|
104 (25.1)
|
97 (18.2)
|
|
Prior consultation regarding HPV vaccines
|
|
|
|
|
Yes
|
339 (35.1)
|
142 (34.3)
|
177 (33.3)
|
0.740
|
No
|
628 (64.9)
|
272 (65.7)
|
355 (66.7)
|
|
Previous sexual experience
|
|
|
|
|
Yes
|
17 (1.8)
|
8 (1.9)
|
9 (1.7)
|
0.782
|
No
|
950 (98.2)
|
406 (98.1)
|
523 (98.3)
|
|
Currently relationship
|
|
|
|
|
Yes
|
147 (15.2)
|
74 (17.9)
|
72 (13.5)
|
0.067
|
No
|
820 (84.8)
|
340 (82.1)
|
460 (86.5)
|
|
Except for the 21 students who had received HPV vaccine before the baseline survey, a total of 946 study subjects were randomly assigned into the intervention and control groups; *1 CNY=0.15 US dollar
Knowledge and awareness towards HPV and HPV vaccines before and after intervention
Table 2 showed that 63.8%, 66.3%, and 60.8% of the participants had heard of HPV, HPV-related diseases, and HPV vaccines, respectively, before the survey. Nearly 70% of the students knew that persistent HPV infection could lead to cervical cancer. However, knowledge of "HPV infection is almost asymptomatic," "HPV infection can be cured by antibiotics," and "HPV infection was very common" were relatively poor, with correct rates of 8.3%, 9.0% and 27.5%, respectively. There was no statistically significant difference in knowledge and awareness of HPV and HPV vaccine between the intervention and control group at baseline, except for correct perception of "persistent HPV infection may lead to cervical cancer" (65.7% vs. 72.9%) (P=0.016).
After the intervention, HPV and HPV vaccine knowledge level was significantly higher in the intervention group than that in the control group (P<0.001). However, the correct rates of "HPV infection is almost asymptomatic" (21.2%), and "antibiotics can cure HPV infection" (29.5%) remained low.
Table 2 Knowledge and awareness towards HPV/HPV vaccines between two groups before and immediately after the intervention
Items
|
Baseline
|
Post-intervention
|
Change percentage point (%)
|
All
N (%)
|
Control
n (%)
|
Intervention
n (%)
|
p
|
Control
n (%)
|
Intervention
n (%)
|
p
|
Heard of HPV
|
|
|
|
|
|
|
|
|
Yes
|
617 (63.8)
|
260 (62.8)
|
337 (63.3)
|
0.863
|
335 (89.1)
|
425 (97.9)
|
<0.001
|
34.6
|
No
|
350 (36.2)
|
154 (37.2)
|
195 (36.7)
|
|
41 (10.9)
|
9 (2.1)
|
|
|
Heard of HPV-related diseases (genital warts, cervical cancer, penile cancer)
|
|
|
|
Yes
|
641 (66.3)
|
275 (66.4)
|
347 (65.2)
|
0.700
|
290 (77.1)
|
410 (94.5)
|
<0.001
|
29.3
|
No
|
326 (33.7)
|
139 (33.6)
|
185 (34.8)
|
|
86 (22.9)
|
24 (5.5)
|
|
|
Heard of HPV vaccine
|
|
|
|
|
|
|
|
Yes
|
588 (60.8)
|
237 (57.2)
|
330 (62.0)
|
0.136
|
311 (82.7)
|
413 (95.2)
|
<0.001
|
33.2
|
No
|
379 (39.2)
|
177 (42.8)
|
202 (38.0)
|
|
65 (17.3)
|
21 (4.8)
|
|
|
Persistent HPV infection can cause cervical cancer
|
|
|
|
|
|
|
Yes
|
678 (70.1)
|
272 (65.7)
|
388 (72.9)
|
0.016
|
270 (71.8)
|
423 (97.5)
|
<0.001
|
24.6
|
No/Unknown
|
289 (29.9)
|
142 (34.3)
|
144 (27.1)
|
|
106 (28.2)
|
11 (2.5)
|
|
|
HPV is mainly transmitted through sexual contact
intercourse
|
|
|
|
|
|
|
Yes
|
516 (53.4)
|
205 (49.5)
|
301 (56.5)
|
0.031
|
197 (52.4)
|
348 (80.2)
|
<0.001
|
23.6
|
No/Unknown
|
451 (46.6)
|
209 (50.5)
|
231 (43.4)
|
|
179 (47.6)
|
86 (19.8)
|
|
|
Condoms can prevent HPV infection
infection
|
|
|
|
|
|
|
|
Yes
|
345 (35.7)
|
139 (33.6)
|
196 (36.8)
|
0.297
|
117 (31.1)
|
210 (48.4)
|
<0.001
|
11.6
|
No/Unknown
|
622 (64.3)
|
275 (66.4)
|
336 (63.2)
|
|
259 (68.9)
|
224 (51.6)
|
|
|
HPV infection is almost asymptomatic
|
|
|
|
|
Yes
|
80 (8.3)
|
38 (9.2)
|
41 (7.7)
|
0.417
|
38 (10.1)
|
92 (21.2)
|
<0.001
|
13.5
|
No/Unknown
|
887 (91.7)
|
376 (90.8)
|
491 (92.3)
|
|
338 (89.9)
|
342 (78.8)
|
|
|
HPV infection may result in oral cancer, anal cancer and genital warts
|
|
|
|
|
Yes
|
547 (56.6)
|
231 (55.8)
|
300 (56.4)
|
0.895
|
222 (59.0)
|
393 (90.6)
|
<0.001
|
34.2
|
No/Unknown
|
420 (43.4)
|
183 (44.2)
|
232 (43.6)
|
|
154 (41.0)
|
41 (9.4)
|
|
|
Most HPV infections can be cured by antibiotics
|
|
|
|
|
|
Yes
|
87 (9.0)
|
35 (8.5)
|
48 (9.0)
|
0.759
|
46 (12.2)
|
128 (29.5)
|
<0.001
|
20.5
|
No/Unknown
|
880 (91.0)
|
379 (91.5)
|
484 (91.0)
|
|
330 (87.8)
|
306 (70.5)
|
|
|
HPV infection is common
|
|
|
|
|
|
|
Yes
|
266 (27.5)
|
119 (28.7)
|
137 (25.8)
|
0.304
|
114 (30.3)
|
342 (78.8)
|
<0.001
|
53.0
|
No/Unknown
|
701 (72.5)
|
295 (71.3)
|
395 (74.2)
|
|
262 (69.7)
|
92 (21.2)
|
|
|
Ideal time for HPV vaccination is before sex debut
|
|
|
|
|
|
|
Yes
|
483 (49.9)
|
192 (46.4)
|
275 (51.7)
|
0.105
|
209 (55.6)
|
417 (96.1)
|
<0.001
|
44.4
|
No/Unknown
|
484 (50.1)
|
222 (53.6)
|
257 (48.3)
|
|
167 (44.4)
|
17 (3.9)
|
|
|
Students' willingness to receive HPV vaccine and reasons for unwillingness before and after the intervention
At baseline, only 2.2% (21/967) of students had received HPV vaccines, and 33.0% (312/946) and 68.8% (651/946) were willing to be vaccinated or willing to encourage their friends to get vaccinated. After intervention, willingness to be vaccinated and willingness to encourage others to take HPV vaccines increased from 36.3% to 45.6% and 71.2% to 84.4%, in the intervention group, respectively. However, the number of vaccinated students remained low, with only 1.6% and 1.8% of students in the control and intervention group, respectively (Fig.2).
The high cost of vaccination (57.7%) and concerns about adverse events (56.0%) were the main reasons for reluctance to be vaccinated at baseline. After the intervention, students in the intervention group had significantly fewer concerns about adverse events (45.5% vs. 60.2%, P=0.001), safety and efficacy of the vaccine (26.8% vs. 42.9%, P<0.001) than the control group, but the high price remained the main factor for students to refuse HPV vaccination (Table 3).
Table 3 Reasons for unwillingness to receive HPV vaccine between intervention and control group before and after the intervention
Reasons for against HPV vaccination
|
Pre-intervention
|
Post-intervention
|
All (n, %)
|
Control group (n, %)
|
Intervention group (n, %)
|
p
|
Control group (n, %)
|
Intervention group (n, %)
|
p
|
Expense of vaccines
|
366 (57.7)
|
168 (56.9)
|
198 (58.4)
|
0.711
|
152 (58.7)
|
160 (68.1)
|
0.031
|
Possible adverse events of HPV vaccine
|
355 (56.0)
|
167 (56.6)
|
188 (55.5)
|
0.771
|
156 (60.2)
|
107 (45.5)
|
0.001
|
No sexual activity
|
243 (38.3)
|
112 (38.0)
|
131 (38.6)
|
0.861
|
93 (35.9)
|
95 (40.4)
|
0.302
|
Doubts on safety and efficacy of HPV vaccine
|
237 (37.4)
|
111 (37.6)
|
126 (37.2)
|
0.905
|
111 (42.9)
|
63 (26.8)
|
<0.001
|
Fear of needling pain
|
133 (21.0)
|
68 (23.1)
|
65 (19.2)
|
0.232
|
59 (22.8)
|
50 (21.3)
|
0.687
|
Vaccination is troublesome
|
130 (20.5)
|
51 (17.3)
|
79 (23.3)
|
0.061
|
40 (15.4)
|
46 (19.6)
|
0.227
|
Factors related to the intention of HPV vaccination
At baseline, five variables were found to be associated with the intention to receive HPV vaccination, as suggested by multivariable logistic regression analysis. Female students from Western China (AOR: 1.51, 95% CI: 1.13-2.02) and students with highly educated parents (AOR: 1.91, 95% CI: 1.34-2.73) were more likely to be vaccinated against HPV. In addition, students who had consulted regarding HPV vaccines (AOR: 1.75, 95% CI: 1.27-2.41), had previous sexual experience (AOR: 5.04, 95% CI: 1.56-16.32) and had heard of HPV vaccines (AOR: 1.94, 95% CI: 1.39-2.71) were more likely to take HPV vaccination. Six factors, including residence place, living expenses, sexual education history, current relationship, heard of HPV, and HPV-related disease, were excluded from the multivariable logistic regression model (Table 4).
Table 4 Factors associated with willingness to be vaccinated with HPV vaccines among female college students at baseline
Variables
|
Total, n
|
Willing to vaccinate, n (%)
|
OR (95% CI)
|
AOR (95% CI)
|
p
|
Research Site
|
|
|
|
|
|
Central
|
509
|
138 (27.1)
|
1.00
|
1.00
|
|
Western
|
437
|
174 (39.8)
|
1.78 (1.35-2.34)
|
1.51 (1.13-2.02)
|
0.006
|
Permanent residence place (>one year)
|
|
|
|
|
|
Rural
|
236
|
56 (23.7)
|
1.00
|
|
|
Urban
|
710
|
256 (36.1)
|
1.81 (1.29-2.54)
|
|
|
Education of parents
|
|
|
|
|
|
Junior high school or below
|
343
|
82 (23.9)
|
1.00
|
1.00
|
0.001
|
Senior high school
|
280
|
86 (30.7)
|
1.41 (0.99-2.01)
|
1.20 (0.83-1.74)
|
0.331
|
College and above
|
323
|
144 (44.6)
|
2.56 (1.84-3.57)
|
1.91 (1.34-2.73)
|
<0.001
|
Living expenses per month (CNY*)
|
|
|
|
|
|
<1,000
|
200
|
48 (24.0)
|
1.00
|
|
|
1,000~2,000
|
662
|
221 (33.4)
|
1.59 (1.10-2.28)
|
|
|
>2,000
|
84
|
43 (51.2)
|
3.32 (1.94-5.68)
|
|
|
Received sexual education
|
|
|
|
|
|
No
|
201
|
48 (23.9)
|
1.00
|
|
|
Yes
|
745
|
264 (35.4)
|
1.75 (1.22-2.50)
|
|
|
Prior consultation regarding HPV vaccines
|
|
|
|
|
|
No
|
627
|
159 (25.4)
|
1.00
|
1.00
|
|
Yes
|
319
|
153 (48.0)
|
2.71 (2.04-3.60)
|
1.75 (1.27-2.41)
|
0.001
|
Previous sexual experience
|
|
|
|
|
|
No
|
929
|
299 (32.2)
|
1.00
|
1.00
|
|
Yes
|
17
|
13 (76.5)
|
6.85 (2.21-21.18)
|
5.04 (1.56-16.32)
|
0.007
|
Currently relationship
|
|
|
|
|
|
No
|
800
|
251 (31.4)
|
1.00
|
|
|
Yes
|
146
|
61 (41.8)
|
1.57 (1.09-2.25)
|
|
|
Heard of HPV
|
|
|
|
|
|
No
|
349
|
74 (21.2)
|
1.00
|
|
|
Yes
|
597
|
238 (39.9)
|
2.46 (1.82-3.34)
|
|
|
Heard of HPV-related disease
|
|
|
|
|
|
No
|
324
|
77 (23.8)
|
1.00
|
|
|
Yes
|
622
|
235 (37.8)
|
1.95 (1.44-2.64)
|
|
|
Heard of HPV vaccine
|
|
|
|
|
|
No
|
379
|
76 (20.1)
|
1.00
|
1.00
|
|
Yes
|
567
|
236 (41.6)
|
2.84 (2.10-3.84)
|
1.94 (1.39-2.71)
|
<0.001
|
*1 CNY=0.15 US dollar; OR, odds ratio; AOR, adjusted odds ratio; CIs: confidence intervals.