Awareness and knowledge associated to Human papillomavirus infection among university students in Morocco: A cross-sectional study.

Worldwide, cervical cancer is a real health issue, however, gaps exist in the public's awareness of the causal role of Human papillomavirus (HPV) in the development of this disease. This study aims to determine the level of awareness, knowledge and the associated factors on HPV among university students in Morocco. A cross-sectional study was conducted with a descriptive and analytical aim, among students attending Ibn Zohr University, in Agadir, Morocco. An interview questionnaire was used to collect information about the participants: demographic data, awareness and level of knowledge on HPV infection, and awareness of cervical cancer. Logistic regression analyses were used to determine the associated factors with awareness and level of knowledge on HPV. A total of 479 students participated in this study (mean age 21.82 ± 2.091). Most participants n = 391 (81.6%) were aware of cervical cancer, while only n = 7 (1.5%) identified HPV as a sexually transmitted infection. Among students, 10.0% (n = 48) were aware of HPV but only half of them n = 23 (47.9%) confirmed that HPV is associated with cervical cancer, and n = 29 (60.4%) showed low knowledge on HPV. Multivariate analysis revealed that HPV awareness has a strong association with a higher level of education (OR 4.04; 95% CI: 1.92-8.52), and with being a biology student (OR 5.20; 95% CI: 2.12-12.73), while high HPV knowledge was only associated with the female gender (OR 3.76; 95% CI: 1.01-13.92). The data suggest that university students in Morocco did not show sufficient knowledge of HPV infection and its consequences. This supports that earlier incorporation of sexual health education programs, especially related to HPV and cervical cancer, must be implemented in the university to reduce the burden of HPV-associated diseases among the population at risk.

Introduction

The papillomavirus belongs to the family of papillomaviridae [1]. They co-evolved over millions of years with a diverse range of animal hosts as well as humans [2]. Human papillomavirus (HPV) is one of the most common causes of sexually transmitted infections (STIs), with the highest rates are found among young and sexually active men and women worldwide [3, 4]. HPVs constitute a group of more than 200 different types associated with benign and malignant neoplasms of the skin and mucosal membranes. Among them, forty different HPV types, known to infect the genital system. These HPV types are subdivided into low-risk types, which cause mainly genital warts; and high-risk types, which were reported to be responsible for almost all cases of cervical cancer (>99.7%) [5]. HPV 16 and HPV 18 are the most carcinogenic HPV types, causing approximately 70% of all cervical cancer cases. Three vaccines with a good safety profile were developed and were shown to be an effective primary prevention strategy against the most common HPV strains. Bivalent (HPV-16 and HPV-18), and quadrivalent (HPV16, 18, 6, and 11), and nonavalent vaccine(HPV 16, 18, 6, 11, 31, 33, 45, 52, and 58) [6]. HPVs were also shown to be associated with 30–60% of head-and-neck cancers, and cause different types of anogenital cancers [7]. Most HPV infections of the cervix are asymptomatic and are cleared within two years [8]. However, cervical cancer is mainly a consequence of the persistence of carcinogenic infections of HPV [9].

Cervical cancer is the fourth most frequently diagnosed cancer in women worldwide, with an estimated 604,000 new cases in 2020, representing 6.5% of all female cancers. It is the fourth leading cause of cancer death in women, with 342,000 deaths worldwide, according to the latest report from the International Agency for Research on Cancer (IARC) in 2020 [10]. This cancer occurs mostly in low and middle-income countries. The highest incidence rates have been recorded in Eastern Africa, while incidence rates are 7 to 10 times lower in North America, Australia/New Zealand, and Western Asia (40.1 per 100,000 in Eastern Africa vs 5.6 per 100,00 in Australia/New Zealand) in 2020 [10].

Cervical cancer is a major health issue in Morocco, with 2165 new cases were diagnosed in 2020. It also comes in the second position, after breast cancer is the leading cause of death by cancer in women, with 1199 death in 2020 [10].

The high frequency of cervical cancer, representing 7.2% of all the female cancers in the country, might be due either to the limited access to health care coverage especially in remote areas in the southern regions of the country or to poor awareness and knowledge about this illness as barriers to use preventive methods [11]. Despite these statistics, cervical cancer is one of the few preventable, and curable human cancer if detected earlier. It could be prevented by primary prevention (large vaccination programs), and secondary prevention approaches (early diagnosis by screening, and by implementing effective treatment programs). In addition, promising prevention strategies based on educational programs to improve knowledge of the pathogenesis of HPV and cervical cancer [12].

In Morocco, there is a lack of data on awareness and knowledge among the general public, on what causes cervical cancer. In this present study, we aim to investigate the level and the associated factors of awareness and knowledge on HPV among higher education students, attending Ibn Zohr University in Morocco, as young adults at risk of contracting HPV infection.

Materials and methods

The study setting and population sample

This cross-sectional study was conducted on the site of the faculty of sciences, Ibn Zohr University (IZU), in Agadir, Morocco, where the majority of the students were attending their curricula. A total of n = 479 participants were selected using a simple random selection process.

The sample size was calculated based on a 5.0% error range, a 95% confidence interval (CI) for a total population of 7000 students in the faculty of sciences, university Ibn Zohr. With an anticipated proportion of knowledge and awareness on HPV deficiency of 50%. The calculation was carried on the website of the sample size calculator: OpenEpi. The minimal sample size required for the study was 365 persons [13].

The questionnaire

Data were collected during a face-to-face interview questionnaire. The questionnaire is a combination of items from published studies on the HPV awareness and knowledge, and from research in the literature [14, 15].

The questionnaire was divided into three main sections. The first section: was designed to collect the socio-demographic information of the participants (i.e., age, gender, marital status, employment status, geographic origin, level of study, and curriculum).

In the second section: participants were first asked to answer the following question (Q1): Do you know any sexually transmitted infections (STIs)? This was followed by a question with “Yes” or “No” response options (Q2): Have you ever heard of cervical cancer? To assess the students’ awareness of HPV infection, we asked them to answer another question with “Yes” or “No” response options (Q3): Have you ever heard of the human papillomavirus (HPV)?

Only the participants that responded “Yes” to the question above (Q3) were considered aware of HPV and were asked to complete section 3 related to knowledge on HPV infection. This section included five questions with Yes/No/Don’t know response options as follows: Is HPV infection symptomatic? (Q4); is HPV infection associated with any disease? (Q5); Is there any association between HPV and cervical cancer? (Q6); Do you think that HPV infection is the main cause of cervical cancer? (Q7); Do you know any prevention strategies against HPV infection? (Q8). We allocated one point for each correct answer, and zero for the incorrect or the “Don’t know” response. The total score was calculated by adding up all scores for the five questions (Q4 to Q8), and possible scores range from 0 to 5. The median score of five for knowledge on HPV was used to categories high and low knowledge.

The scores higher than the median (median = 2) were categories as “High knowledge”; while “Low knowledge” referred to scores equal or lower than the median [16]. The data were archived as digital files.

The statistical analysis

Descriptive statistics include frequencies and percentages for categorical variables, mean and standard deviation (SD) for continuous variables were calculated. Student test, Chi-square (χ2) and Fisher’s exact analyses were used to identify the associated sociodemographic variables to HPV awareness, knowledge on HPV, and cervical cancer awareness. P-values <0.05 were considered significant.

Odds ratio (OR), p-value and 95% confidence intervals (CI) were obtained using logistic regression models. Univariate and multivariate logistic regression analyses were used to determine the significant associations between the socio-demographic variables and awareness of HPV infection, and the level of knowledge on HPV infection. Variables that exhibited statistical significance at the 0.2 level in the univariate analysis were included in the multivariate analysis using a logistic regression model adjusted for potential confounders [17]. Statistical significance was defined as p-value < 0.05.

The collected data were analyzed using statistical analysis software (IBM SPSS statistics version 13.0, New York, NY).

Ethics approval and consideration

The objective of the study was fully explained to the participants before the data collection. An informed written consent was obtained from each participant. Participating in the survey was voluntary and anonymous. This research was fully approved by the Bioethics consultative commission of the Faculty of Sciences of Agadir (BECC-FSA Ref. No: FCR-CS-05/2021-0001).

Results

a) Sociodemographic characteristics of the participants

A total of n = 479 students were included in this study (the complete data were shown in S1 Table). The age of the population was comprised between 17 to 28 years, with a mean age at 21.82 ± 2.091. The male population was n = 243 (50.70%), and the female population was n = 236 (49.3%). The majority of the participants were full-time students n = 475 (99.20%), single n = 474 (99.00%), and came from urban areas n = 353 (73.7%). More than half of them n = 261 (54.50%) were pursuing their studies in biology curricula, and the undergraduate students accounted for n = 430 (89.80%) of all the participants (Table 1).

Table 1

Characteristics of the population in relation to the awareness of HPV infection and cervical cancer.

Variables	Number (%) n = 479	HPV Awareness n = 479Have you ever heard of HPV?			Cervical Cancer Awareness n = 479Have you ever heard of CC?
		Yes n(%)	No n(%)	p-value	Yes n(%)	No n(%)	p-value
Age (mean± SD)	21.82±2.09	22.81±2.23	21.71±2.04	0.860	21.86±2.14	21.61±1.82	0.176
17–21	213(44.5)	12 (5.6)	201 (94.4)	0.004*	167 (78.4)	46 (21.6)	0.103
22–28	266 (55.5)	36(13.5)	230 (86.5)		224 (84.2)	42 (15.8)
Gender
Men	243 (50.7)	23 (9.5)	220 (90.5)	0.681	181 (74.5)	62(25.5)	< 0.001*
Women	236 (49.3)	25 (10.6)	211 (89.4)		210(89.0)	26(11.0)
Marital status
Single	474 (99.00)	47 (9.9)	427(90.1)	0.412	386(81.4)	88(18.6)	0.590
Married	5 (1.00)	1 (20.0)	4 (80.0)		5 (100.0)	0 (0.0)
Employed
Yes	4 (0.8)	1 (25.0)	3 (75.0)	0.345	4 (100.0)	0 (0.0)	1.000
No	475 (99.20)	47 (9.9)	428(90.1)		387(81.5)	88(18.5)
Geographic origin
Urban	353 (73.70)	37(10.5)	316(89.5)	0.574	290(82.2)	63(17.8)	0.620
Rural	126 (26.30)	11 (8.7)	115(91.3)		101(80.2)	25(19.8)
Level of education
Undergraduate	430 (89.80)	31 (7.2)	399(92.8)	<0.001*	346(80.5)	84(19.5)	0.051
Graduate	49 (10.20)	17(34.7)	32 (65.3)		45 (91.8)	5 (8.2)
Curriculum
Non-biology	261 (54.50)	6 (2.8)	212(97.2)	<0.001*	163(74.8)	55(25.2)	< 0.001*
Biology	218 (45.50)	42(16.1)	219(83.9)		228(87.4)	33(12.6)

n = number of participants. % percentage. HPV = Human Papillomavirus. CC = Cervical Cancer.

*Statistical significance

b) The awareness of the population related to HPV infection and its association with cervical cancer

The results showed that the acquired immune deficiency syndrome (AIDS) is the most cited sexually transmitted infection (STI) among all the STIs mentioned by the students (Q1). Among the respondents n = 459 (95.80%) mentioned AIDS in the first place, followed by syphilis n = 83 (17.30%), and hepatitis B which was mentioned by only n = 32 (6.70%) of the students. Other STIs have been mentioned such as herpes n = 4 (0.80%), Chlamydia spp. n = 3 (0.60%) and n = 1 Trichomonas spp. (0.20%). Regarding Human papillomavirus (HPV) infection, we found that only 7 students (1.50%) knew that HPV infection is an STI.

Students were also asked if they knew about cervical cancer (Q2). Surprisingly, the vast majority of them have already heard about cervical cancer (81.6%, 391 out of 479), and significant differences were reported between the group who have heard about cervical cancer and the group who haven’t heard about it, in relation to: gender (p< 0.001) and curriculum (p< 0.001) (Table 1). However, only n = 48 (10.0%) replied to have already heard about HPV (Q3). These students were aware of HPV infection. Differences in HPV awareness group by age (p = 0.004), level of education (p = 0.000) and curriculum (p = 0.000) were significant (Table 1).

C) The knowledge of the population related to HPV infection and its association with cervical cancer

The results showed that among the students who previously have heard about HPV infection, n = 29 (60.4%) knew that HPV infection is asymptomatic (Q4). Only 22 out of 48 students (45.8%) knew that HPV infection can be associated with other diseases (Q5). The link between HPV and cervical cancer was confirmed by n = 23 (47.9%) of the participants (Q6). More than half n = 26 (54.2%) responded that infection with HPV is the leading cause for the development of cervical cancer (Q7). Finally, the majority of the students n = 33 (68.8%) were unable to suggest any prevention strategy against the HPV infection (Q8). Regarding the knowledge about HPV infection, the participants could be divided into two groups: Low knowledge group n = 29 (60.4%) and high knowledge group n = 19 (49.6%) (Table 2).

Table 2

Characteristics of the population in correlation with the knowledge related to HPV and cervical cancer.

Variables	Number (%) n = 479	Knowledge on HPV n = 48
		Low n(%) n = 29	High n(%) n = 19
Age
Mean ± SD	21.82 ± 2.091	22.69±2.34	23±2.10
17–21	213 (44.50)	7 (58.3)	5 (41.7)
22–28	266 (55.50)	22 (61.1)	14 (38.9)
Gender
Men	243 (50.70)	18 (78.3)	5 (21.7)
Women	236 (49.30)	11 (44.0)	14 (56.0)
Marital status
Single	474 (99.00)	29 (61.7)	18 (38.3)
Married	5 (1.00)	0 (0.0)	1 (100.0)
Employed
Yes	4 (0.8)	0 (0.0)	1 (100.0)
No	475 (99.20)	29 (61.7)	18 (38.3)
Geographic origin
Urban	353 (73.70)	21 (56.8)	16 (43.2)
Rural	126 (26.30)	8 (72.7)	3 (27.3)
Level of education
Undergraduate	430 (89.80)	22 (71.0)	9 (29.0)
Graduate	49 (10.20)	7 (41.2)	10 (58.8)
Curriculum
Non-biology	261 (54.50)	23 (54.8)	19 (45.2)
Biology	218 (45.50)	6 (100.0)	0 (0.0)

n = number of participants. % percentage. HPV = Human Papillomavirus. CC = Cervical Cancer. *Statistical significance.

D) Factors affecting the awareness and the knowledge associated to HPV infection

To investigate the association between the awareness about HPV infection and some key features of the population, we performed univariate logistic regression statistical analyses (S2 Table).

This analysis showed that HPV awareness correlated positively with the age of the participants, their curriculum, and their level of study.

The awareness about HPV infection was higher in the population of the students aged between 22 and 28 years, compared to those aged between 17 and 21 years old (13.5% vs 5.6%) (OR = 2.62; 95% CI = [1.32–5.17]; p = 0.005). In addition, graduate students were more likely to be aware of HPV infection compared to undergraduate students (OR 6.83; 95% CI = [3.42–13.66] p <0.001). Students with a biology curriculum knew more about HPV compared to non-biology curriculum students (16.1% vs 2.8%) (OR = 6.77; 95% CI = [2.82–16.27]; p <0.001). To confirm these results, we entered the most significant variables into a multivariate model. This model showed that the high level of education (OR = 4.04; 95% CI = [1.92–8.52]; p = 0.001), and the nature of the curriculum (OR = 4.92; 95% CI = [2.12–12.73]; p = 0.001) remained significantly associated factors with HPV awareness (Table 3).

Table 3

Multivariate logistic regression analysis to examine the factors associated with HPV awareness and knowledge.

Variables	HPV Awareness		HPV Knowledge
	Multivariate analysis		Multivariate analysis
	aOR (CI 95%)	p-value	aOR (CI 95%)	p-value
Age categories
17–21	1	0.096	-	-
22–28	1.85 (0.89–3.83)
Gender
Men	-	-	1	0.047*
Women			3.76 (1.01–13.92)
Level of education
Undergraduate	1	< 0.001*	1	0.145
Graduate	4.04 (1.92–8.52)		2.65 (0.71–9.81)
Curriculum
Non-biology	1	< 0.001*	-	-
Biology	5.20 (2.12–12.73)

%percentage. HPV = Human Papillomavirus, CI = Confidence interval. aOR = Adjusted Odds ratio.

1: Reference category.

*Statistical significance

The univariate logistic regression analysis revealed that knowledge about HPV was associated significantly with the gender and the level of study (S2 Table). Females were more likely to have higher knowledge about HPV compared to males (56.0% vs 21.7%) (OR = 4.58; 95% CI = [1.29–16.26]; p = 0.019). Education level had a positive effect on the knowledge related to HPV, graduate students were more likely to have better knowledge of HPV compared to undergraduate students (OR = 3.49; 95% CI = [1.01–12.05]; p = 0.048). The multivariate analysis showed that only gender remained significantly associated factor with HPV knowledge (OR = 3.76; 95% CI = [1.01–13.92]; p = 0.047) (Table 3).

Discussion

Very limited reports investigated the awareness of STIs, particularly the HPV infection and its association with cervical cancer among higher education students in Morocco, despite this part of the population was the most concerned by such issues.

As a first approach to assess the awareness of HPV infection, the students were asked to indicate which STIs they already knew. This question was mainly asked to find out if the students can identify HPV infection among STIs. We showed that the majority of students have little knowledge concerning STIs. In addition, very few of them knew that HPV infection is STI (1.50%). However, a high proportion of them (95.8%) were aware that AIDS is STI. AIDS was the best known STI, which might be the result of the massive educative programs through the media, schools, and health professionals which enhanced awareness of the general population about it. Similarly, it was reported in Egypt that 95.9% of the students knew about AIDS, but they showed a poor knowledge about sexual health issues [18]. By contrast, students in the UK had a higher level of knowledge about STIs [19]. This might be explained by the effect of cultural differences and religious sensitivities between countries, which limited considerably sexual education and awareness among students. Among the students, 81.6% were aware of cervical cancer. This awareness was lower than the 94.2% obtained in the study conducted in the Netherlands, however, higher than the 56.4% reported among students in Nigeria and 33.3% in South Africa (33%) [20-22]. The existence of effective educational programs to raise awareness of cervical cancer in the European countries might explain the high level of awareness compared to the African countries.

In this study, only 10.0% of the students reported having heard about HPV and showed a poor level of HPV knowledge. This result was lower than a study conducted among Moroccan students (33.7%), but they also showed a poor level of HPV knowledge [15]. This disparity in HPV awareness in the same country can be explained by the fact that students in southern Morocco live in areas with fewer healthcare facilities. Such low HPV awareness has also been reported by several studies, among university students in Nigeria (17.7%), Portugal (55.4%), Malaysia (21.7%), in The Netherlands (17.7%), among female medical students in Ethiopia (50.6%), and they all showed a low level of HPV knowledge [20, 21, 23–25]. Contrary to this finding, a study carried out in the USA reported that (78.0%) had heard of HPV and showed a relatively high HPV knowledge [26]. Besides that, our finding associated more HPV awareness with being a biology student and having high educational attainment. The study conducted in Morocco, the authors agreed that education level had a positive effect on HPV awareness [15]. A similar finding was reported by a study in India where biology students have shown more awareness towards HPV when compared to non-biology students [14]. A significant association was found between being a health science student and having heard about HPV in the study conducted in Portugal [23]. This had been also agreed by a study in the Netherlands where medical students were more aware of HPV than non-medical students [20]. These results suggest a misunderstanding or lack of sexual health background among non-biology students which explains why they showed low HPV awareness compared to biology students. It also seems plausible that students with high educational levels have more chances to hear about HPV than those with lower educational levels. We might find a positive correlation between the age and their level of education. However, it remains questionable at what extent age can be regarded as an independent risk factor functioning as confounder in the awareness-level of education relationship.

Our finding also revealed that women showed better knowledge about HPV infection than men did, which is consistent with the finding reported by researchers in Portugal [23]. The poor HPV knowledge among men highlights that they are less knowledgeable about sexual health issues than women. Indeed, it is very important to intensify HPV knowledge among all the students, especially men because they participate in the transmission and the acquisition of HPV infection.

This present study highlights a poor awareness and knowledge towards STIs in particular HPV infections among university students. Those students who were supposed to be the most knowledgeable showed a big gap in the understanding of their sexual health. Our findings suggest the urgent need for well-designed educational interventions and university campaigns to improve HPV, STIs, and cervical cancer awareness. Targeting higher education students as future educators, parents, and community members will guarantee the next generations with more awareness towards HPV and its negative outcomes.

Conclusion

In the current study, we showed that, the majority of the students 391 out of 479 have heard of cervical cancer, but only 23 out of 479 students were aware that HPV infection is associated with the development of cervical cancer.

Indeed, we found that the most significant factors associated with better awareness about HPV were respectively: (i) the high level of education; (ii) the attendance to curricula related to biological science, while the only associated factor with high knowledge on HPV was the female gender.

Accordingly, we believe that the early incorporation of sexually communicable diseases teaching programs in higher education in Morocco will improve the awareness of young educated people, and reduce the burden of HPV associated diseases among this population at risk.

Study data n = 479 participants.

(XLSX)

Click here for additional data file.

Logistic regression analysis: Detailed univariate and multivariate analysis of the data.

(DOCX)

Click here for additional data file.

25 Jan 2022

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Reviewer #1: The manuscript is well written and has potential.

However, a few typographical and technical errors have been noted in the attached document.

Some highlights to address:

1. Please clearly state your sample size

2. Maintain one style of citation

Good job

Reviewer #2: The manuscript provides a logical flow from the introduction to the study objectives and conclusion.

The manuscript is well presented and written in standard comprehensible English. However, it can still benefit from structural rearrangement of some of the sentences to make readability easier, especially the result and discussion section.

It was mentioned that the study data is available without restriction but information on where and how it could be accessed was not provided.

The section on material and methods: More clarity should be provided abut the mode of questionnaire administration. How was this done? (self-administration, facilitated or online assessment). This need to be clear. The section on the questionnaire could probably focused more on the description of the questionnaire and approach to the response which are more useful for replicability rather than on specific content of the questionaire

Reviewer #3: Thanks dear authors. The topic and findings are revelant. Kindly find my comments for improvment and question that need clarification.

1. Title:

Knowledge and Awareness toward Human Papillomavirus and Cervical Cancer(CC): A Cross-sectional Study Among University Students in Morocco. This does not suggest that you will find the factors associated with awarness and knowelege about HPV and CC.

2. Introduction:

To what extent are university students at risk for HPV related infections such as cervical cancer? This information can justfy your research if included in the introduction.

3. Methods section:

how do calculate the sample size of 479 students and allocate in to faculities and lebow? Describe the smaple size determination and prcudure.

The way you describe measurement of knowledge in your research is intersting. However, the cut of poit 3 correct answers needs a reference or justification?

4. Results:

The presentation of your result shall be according to your objectives. for example

a) describe sociademographic and reproductive charactrestics of your participants

b) their awarness about HPV and CC

C) Their knowledge about HPV andCC

D) Factors affecting their knowledge

So tabel 1 need to be split

Why class year is not recoreded?as long as awarness of the first year and graduating class student won't be the same

On table2: the AOR foe age and level of study are mispolaced. correct them. again the insteady of writting ref, use 1

In table2: the uni and multivariate analusis result should be presented separately if you must report. For me Univariate is not needed. The p- value and confidence interval should be reported in the multivariate analysis.You need to presnt also ont only about HPV but also CC. In general table 2 can not be interpretued correctly, there are missing elemests. i.e the CI sould be consistent with the response of the outcome variable. This needs revision

5 Discussion: is good

6. references

Replace references older than 2017 for article or 2002 for books with recent onces

Reviewer #4: Critical review of the manuscript titled

”Knowledge and Awareness toward Human Papillomavirus and Cervical Cancer: A Cross-sectional Study Among University Students in Morocco”

submitted to PLOS ONE

The authors report the results of a questionnaire survey on awareness and knowledge of HPV infection, cervical cancer and their relationship, conducted among university students in Agadir, Morocco. The topic is an important public health issue but the coverage of the study is very limited, the study population is not representative even for the students at the university and the development of the questionnaire is unclear.

Major comments

1) “The participants were selected using a simple random selection process. However, the population of students targeted was mainly those attending courses in the Faculty of Sciences.” (page 4, lines 20-21). The two sentences contradict each other. The source population is unclear; therefore, the study population seems to be not representative for any population group.

2) “This was followed by an open-ended question with “Yes” or “No” response options…” (page 5, lines 6-7). A question with Yes/No options is not an open-ended question.

3) The development of the survey tool is not explained. Is it a standardized questionnaire? Was it pilot tested? Were questions from other surveys adopted? How was the cut-off level of knowledge determined?

4) Why was age dichotomized and not handled as a continuous variable? This approach introduced loss of information.

5) How could it happen that fewer participants knew the association between HPV and cervical cancer than those who knew that HPV is its leading cause? It seems a contradiction.

6) Age essentially correlates with the level of education; therefore, it is questionable whether age can be regarded as an independent risk factor functioning as confounder in the awareness-level of education relationship.

Minor comments

1) The aim of the study is not clearly phrased in the Abstract.

2) “Logistic regression analyses were to determine...” (page 2, line 8). Insert “used”.

3) “…higher level of study…” (page 2, line 14 and at several other places). I suggest using “level of education” throughout.

4) “University student” (Keywords) should not be capitalized.

5) “Bivalent (HPV-16 and HPV-18), and quadrivalent (HPV-16, HPV-18, HPV-6, and HPV-11), and nonavalent vaccine targets the same HPV types as the quadrivalent vaccine as well as types (31, 33, 45, 52, and 58) [8,9].” (page 3, lines 12-14). The sentence is incorrectly phrased.

6) “…for categorical variables. Mean and…” (page 5, line 21) should be “…for categorical variables, mean and…”.

7) “adjusted by potential confounders” (page 6, line 4) should be “adjusted for potential confounders”.

8) “[Table 1]” (page 7, line 8) should be “(Table 1).

9) Asterisk should rather be used to highlight significance in Table 1.

10) There is no point to report p value if CI95% is reported in Table 2.

11) “…(50.6%) among female medical students in Ethiopia [29],…” (page 12, line 5) should be “…among female medical students in Ethiopia (50.6%) [29],…”.

12) “…women showed good knowledge…” (page 12, line 18) should be “…women showed better knowledge…”.

Summary

The manuscript discusses an important public health topic but the study setting is very limited, not representative, and the development of the survey instrument is unclear. Under these circumstances, the results cannot lead to solid scientific conclusions.

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Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

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Submitted filename: Manuscript.docx

Click here for additional data file.

25 Feb 2022

Dear Muhammad Tarek Abdel Ghafar,

I would like to thank you and the reviewers for the useful comments on our article. I now have edited the manuscript to address the concerns raised by the reviewers. Accordingly, please find below the response, point by point.

I hope that the manuscript, in its actual form, meets the standards for publication in PLOS ONE.

I am looking forward to hearing from you soon,

Sincerely yours,

EL MANSOURI Nezha.

Academic editor:

Point 1:

Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Corrected. We hopefully have no divergences from the style requirements now.

Point 2:

Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed).

We amended the ethics statements to emphasize that all participants gave written consent, line 136-137 (Simple Markup track changes).

An informed written consent was obtained from each participant when they agreed to be included in this study. The ethics statement was also amended in the submission form.

Point 3:

We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Thank you for the remark.

I would like to let you know that the box referring to “the additional data availability information” was ticked by mistake during the submission online. We removed this tick mark. Instead, all relevant data are now available in the manuscript and in the supporting information files.

Reviewer #1

The manuscript is well written and has potential. However, a few typographical and technical errors have been noted in the attached document.

All highlighted typographical and technical errors have been corrected. We thank the reviewer for helping us.

Some highlights to address:

Point 1:

Please clearly state your sample size

Amended, we added the following sentence in line 92 (Simple markup track changes): A total of n= 479 participants were selected using a simple random selection process.

Point 2:

Maintain one style of citation

Amended.

Reviewer #2

Point 1:

The manuscript is well presented and written in standard comprehensible English. However, it can still benefit from structural rearrangement of some of the sentences to make readability easier, especially the result and discussion section.

Amended.

Point 2:

It was mentioned that the study data is available without restriction but information on where and how it could be accessed was not provided.

We have sent the study data (Excel file) as a supporting information file.

The section on material and methods:

Point 3:

More clarity should be provided about the mode of questionnaire administration. How was this done? (self-administration, facilitated or online assessment). This need to be clear. The section on the questionnaire could probably focused more on the description of the questionnaire and approach to the response which are more useful for replicability rather than on specific content of the questionnaire.

The administration of the questionnaire was a face-to-face interview questionnaire done by our team members, who also helped in clarifying questions for the students. We added a sentence in the manuscript that emphasize the type of questionnaire and how it was implemented on line 99 (simple markup track changes).

Reviewer #3

Point 1:

Title: Knowledge and Awareness toward Human Papillomavirus and Cervical Cancer (CC): A Cross-sectional Study Among University Students in Morocco. This does not suggest that you will find the factors associated with awareness and knowledge about HPV and CC.

Thank you for your comment. We have changed the title to reflect more the study objectives.

Corrected title: “Human Papillomavirus knowledge, awareness and associated factors: A cross-sectional study among university students in Morocco.”

Point 2:

Introduction: To what extent are university students at risk for HPV related infections such as cervical cancer? This information can justify your research if included in the introduction.

Cervical cancer is a consequence of the persistence of HPV infection which is the most common sexually transmitted infection worldwide. The highest rates of HPV infection are found among young and sexually active men and women. It was also shown that HPV infection prevalence decreased with increasing age from a peak prevalence in younger women (≤25 years of age) (Smith JS et al., Age-Specific Prevalence of Infection with Human Papillomavirus in Females: A Global Review. J Adolesc Heal. 2008 43:5–25). Students at the university are young adults and at the age of sexual activity, and the probability of contracting HPV infection during this period is high. We have added this information in the introduction on lines 52-53 and 87 (simple markup track changes).

Point 3:

Methods section: how do calculate the sample size of 479 students and allocate in to faculities and lebow? Describe the sample size determination and prcudure.

We have added information on the manuscript to clarify the sample size calculation, lines 93-97 (simple markup track changes). As follow:

The size of the sample was calculated based on a 5.0% error range, a 95% confidence interval (CI) for a total population of 7000 students in the faculty of sciences, university Ibn Zohr. With an anticipated proportion of knowledge and awareness on HPV deficiency of 50%. The sample size was calculated using the website OpenEpi https://www.openepi.com/Menu/OE_Menu.htm. The minimal sample size required for the study was 365 persons.

The way you describe measurement of knowledge in your research is interesting. However, the cut of point 3 correct answers needs a reference or justification?

We have added information in the manuscript to clarify the cut of point 3, on lines 115-121 (simple markup track changes), as follow:

We allocated one point for each correct answer, and zero for the incorrect or the “Don’t know” responses. The total score was calculated by adding up all scores for the five questions (Q4 to Q8), and possible scores range from 0 to 5. The scores higher than the median (median=2) (Higher or equal than 3 correct answers) were designated as categories of “High knowledge”. By contrast, “Low knowledge” referred to scores equal or lower than the median or (Lower than 3 correct answers) (Tusimin M et al. Sociodemographic determinants of knowledge and attitude in the primary prevention of cervical cancer among University Tunku Abdul Rahman (UTAR) students in Malaysia: Preliminary study of HPV vaccination. BMC Public Health. 2019;19(1):1–6).

Point 4:

Results: The presentation of your result shall be according to your objectives. For example:

a) describe sociodemographic and reproductive characteristics of your participants

b) their awareness about HPV and CC

C) Their knowledge about HPV and CC

D) Factors affecting their knowledge

So table 1 need to be split

We thank the reviewer for the constructive feedback. All the suggested changes in the results section structure and table 1 have been made. Table 1 is split into Tables 1 and 2, on pages 7 and 8 respectively.

However, regarding point (c), our work was mainly focused on what causes CC, instead of the knowledge toward CC.

Why class year is not recorded? as long as awareness of the first year and graduating class student won't be the same

We did record class year for each student during the data collection as follow: 1st year, 2nd year, 3rd year and masters, and then we considered (1st year, 2nd year, 3rdyear = undergraduate and masters= graduate). Indeed, logistic regression is the type of analysis to use when we work with binary data. Therefore, we categorized all the independent variables in our study into two groups. We omitted this details in the manuscript in order to keep the independent variable (Level of education) dichotomous.

On table2: the OR for age and level of study are misplaced. correct them. again the instead of writing ref, use 1

Corrected.

In table2: the uni and multivariate analysis result should be presented separately if you must report. For me Univariate is not needed. The p- value and confidence interval should be reported in the multivariate analysis. You need to present also ont only about HPV but also CC. In general table 2 cannot be interpreted correctly, there are missing elements. i.e the CI should be consistent with the response of the outcome variable. This needs revision.

As required above, we have modified the table accordingly (Table 2 is now Table 3 on page 10).

References: Replace references older than 2017 for article or 2002 for books with recent ones

As required, the references were updated in the introduction section.

Reviewer #4

Major comments

Point 1:

“The participants were selected using a simple random selection process. However, the population of students targeted was mainly those attending courses in the Faculty of Sciences.” (page 4, lines 20-21). The two sentences contradict each other. The source population is unclear; therefore, the study population seems to be not representative for any population group.

Thank you for your comment. We have corrected this in the manuscript on line 90-92 as follow:

- This cross-sectional study was conducted on the site of the faculty of sciences, Ibn Zohr University (IZU), in Agadir, Morocco, where the majority of the students were attending their curricula. A total of n= 479 participants were included using a simple random selection process.

- The choice of the population: In fact, university students are young adults and at the age of sexual activity, making them at high risk of contracting HPV infection.

Point 2:

“This was followed by an open-ended question with “Yes” or “No” response options…” (page 5, lines 6-7). A question with Yes/No options is not an open-ended question.

Corrected in the manuscript on lines 106, 108 and 112 (Simple markup track changes).

Point 3:

The development of the survey tool is not explained. Is it a standardized questionnaire? Was it pilot tested? Were questions from other surveys adopted?

The questionnaire is a combination of items adapted from previously published studies below:

- Zouheir Y et al., Knowledge of Human Papillomavirus and Acceptability to Vaccinate in Adolescents and Young Adults of the Moroccan Population.

J Pediatr Adolesc Gynecol. 2016;29(3):292–8;

- Rashid S et al., Knowledge, awareness and attitude on HPV, HPV vaccine and cervical cancer among the college students in India.

PLoS One. 2016;11(11):1–11.)

We added this modifications in the manuscript on lines: 99-101.

How was the cut-off level of knowledge determined?

We have added information in the manuscript to clarify the cut of point 3, on lines 115-121, (simple markup track changes), as follow:

We allocated one point for each correct answer, and zero for the incorrect or the “Don’t know” responses. The total score was calculated by adding up all scores for the five questions (Q4 to Q8). The possible scores range is from 0 to 5. The scores higher than the median (median=2; Higher or equal than 3 correct answers) were considered as categories of “High knowledge”. By contrast, “Low knowledge” referred to scores equal or lower than the median or (Lower than 3 correct answers) (Tusimin M et al. Sociodemographic determinants of knowledge and attitude in the primary prevention of cervical cancer among University Tunku Abdul Rahman (UTAR) students in Malaysia: Preliminary study of HPV vaccination. BMC Public Health. 2019;19(1):1–6)).

Point 4:

Why was age dichotomized and not handled as a continuous variable? This approach introduced loss of information.

Corrected. The independent t-test was performed when we added age as a continuous variable (Table 1 and Table 2.). However, in the logistic regression analysis age was dichotomised based on the mean to facilitate the analysis (Table 3).

Point 5:

How could it happen that fewer participants knew the association between HPV and cervical cancer than those who knew that HPV is its leading cause? It seems a contradiction.

The present study reveals that 60.4% of the students who have heard about HPV infection, did show a low knowledge about the virus itself. Those students, through their responses, showed that there is a gap in their understanding of this infection and of its consequences (i.e. association between HPV and CC). In addition, due to the nature of the answers proposed (i.e. Yes/ No/ Don’t know) we might have overestimated the level of knowledge of our surveyed population. This may constitute one of the limitations of this study. Indeed, open questions are needed to avoid influencing the answers given by the participants.

Point 6:

Age essentially correlates with the level of education; therefore, it is questionable whether age can be regarded as an independent risk factor functioning as confounder in the awareness-level of education relationship.

We agree that level of education correlate with age; this has been emphasized in the discussion section, on lines 247-250 (Simple markup track changes).

Minor comments

We thank the reviewer for spotting these errors and for their constructive feedback. All the suggested minor comments have been corrected and highlighted in the manuscript (red font).

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

14 Mar 2022

27 Apr 2022

Dear Muhammad Tarek Abdel Ghafar,

I would like to thank you and the reviewers for the useful comments on our manuscript. I now have edited the manuscript to address the concerns raised by the reviewers. Accordingly, please find below the response, point by point.

I hope that the manuscript in its actual form meets the standards for publication in PLOS ONE.

I am looking forward to hearing from you soon,

Sincerely yours,

EL MANSOURI Nezha.

Academic editor:

Please review your reference list to ensure that it is complete and correct.

Amended. Thank you.

we have completed the missing information for each reference. We replaced the reference number [13] on lines 307-309 ( (simple markup track changes) : OpenEpi:Sample Size for X-Sectional,Cohort,and Clinical Trials [Internet]. [cited 2022 Feb 21]. Available from: http://www.openepi.com/SampleSize/SSCohort.htm, with Sullivan KM, Dean A, Minn MS. OpenEpi: A web-based epidemiologic and statistical calculator for public health. Public Health Reports. 2009; 124(3): 471–474. doi: 10.1177/003335490912400320

Reviewer #2

Need for a minor correction at Line 105. A reference to a "Yes" or "No" question is not open ended.

Amended. Thank you.

Reviewer #3

Point 1

Knowledge comes after awareness.

Amended

Corrected title: “Awareness and knowledge associated to Human Papillomavirus infection among university students in Morocco: A cross-sectional study”.

Point 3

Analysing the associated factors for awareness and knowledge is just repetition.

In the present study awareness and knowledge related to HPV infection were investigated separately, as well as the associated factors. Awareness on HPV was investigated using a Yes or No question “Have you ever heard of Human Papillomavirus (HPV)? This question was asked to the whole population included in this study. By contrast, the knowledge related to HPV infection was investigated exclusively among students that responded “Yes” to the previous question (i.e. Have you ever heard of Human Papillomavirus?)

Point 3

The tabular presentation needs correction.

The logical order of presentation should be according to your objectives.

First description of study participants, then knowledge, then the factors. The others are not relevant. Try to describe what is the level of knowledge about HPV/CC and the associated factors.

We investigated the level of knowledge related to HPV infection and the factors that might be associated. However, the adopted questionnaire did not investigate specifically the level of knowledge related to cervical cancer. Indeed, our investigation focused on awareness and knowledge related only to HPV infection and the factors that might be associated.

The Chi Square is not important. you already categorise your dependent variable knowledge as high and low. So, you can use logistic regression.

Amended on lines 212-214 (simple markup track changes), and in table 2.

Thank you.

Submitted filename: Response to Reviewers.docx

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12 Jun 2022

23 Jun 2022

Academic editor:

Please cite the supplementary tables within the text.

Amended, we cited the supplementary tables on lines 142-143, 187 and 200 (simple markup track changes).

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

27 Jun 2022

Awareness and knowledge associated to Human Papillomavirus infection among university students in Morocco: A cross-sectional study

PONE-D-21-38027R3

Dear Dr. EL MANSOURI,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Muhammad Tarek Abdel Ghafar, M.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

30 Jun 2022

PONE-D-21-38027R3

Awareness and knowledge associated to Human Papillomavirus infection among university students in Morocco: A cross-sectional study

Dear Dr. EL MANSOURI:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

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on behalf of

Prof Muhammad Tarek Abdel Ghafar

Academic Editor

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