|Year : 2020 | Volume
| Issue : 6 | Page : 2950-2957
Parental acceptance of human papillomavirus vaccination for adolescent girls in Lagos, Nigeria
Kabiru A Rabiu1, Taiwo G Alausa2, Fatimat M Akinlusi1, Nosimot O Davies3, Khadijah A Shittu2, Oluwarotimi Ireti Akinola1
1 Department of Obstetrics and Gynaecology, Lagos State University College of Medicine, Ikeja, Lagos State, Nigeria
2 Department of Obstetrics and Gynaecology, Lagos State University Teaching Hospital, Ikeja, Lagos State, Nigeria
3 Department of Haematology and Blood Transfusion, Lagos University College of Medicine, Idi-Araba, Lagos State, Nigeria
|Date of Submission||16-Jan-2020|
|Date of Decision||12-Mar-2020|
|Date of Acceptance||07-Apr-2020|
|Date of Web Publication||30-Jun-2020|
Dr. Kabiru A Rabiu
Department of Obstetrics and Gynaecology, Lagos State University College of Medicine, Ikeja, Lagos State
Source of Support: None, Conflict of Interest: None
Background and Aims: Human papillomavirus (HPV) vaccination is recommended for adolescent girls and would offer a long-term solution to cervical cancer especially in developing countries. However, parental perception and acceptance is a critical success factor. This study examined the degree of parental acceptance of HPV vaccination for adolescent secondary-school girls in Lagos, Nigeria. Materials and Methods: A descriptive cross-sectional survey of adolescent girls' parents was undertaken in two urban and two rural secondary schools in Lagos. Univariate and multivariate analysis were carried out using logistic regression to determine correlates of parental acceptance of HPV vaccine. Results: Of the 318 respondents, 45.9% had poor knowledge of cervical cancer and HPV infection, whereas 29.6% had good knowledge. Majority (54.7%) also had poor knowledge of HPV vaccine, whereas 26.7% had good knowledge. Most (72%) would vaccinate their daughters if vaccines were free, whereas only 35.5% would, if not free. Poor knowledge of cervical cancer and HPV infection significantly reduced the likelihood of vaccination even if free (adjusted odds ratio [OR] =0.48; 95% confidence interval [CI] =0.24–0.94; P = 0.0325), whereas good knowledge of HPV vaccines (adjusted OR = 6.11; 95% CI = 1.37–27.34; P = 0.018) and tertiary education in the mother (adjusted OR = 29.17; 95% CI = 3.98–214.08; P = 0.0009) increased the likelihood, if not free. Conclusion: HPV vaccination was acceptable to most parents only if offered free. Poor knowledge of cervical cancer, HPV infection, and vaccine may hinder acceptability. It is recommended that HPV vaccination is offered free through the National Programme on Immunization in Nigeria.
Keywords: Adolescents, cervical cancer, human papillomavirus vaccine, Nigeria, parental acceptance
|How to cite this article:|
Rabiu KA, Alausa TG, Akinlusi FM, Davies NO, Shittu KA, Akinola OI. Parental acceptance of human papillomavirus vaccination for adolescent girls in Lagos, Nigeria. J Family Med Prim Care 2020;9:2950-7
|How to cite this URL:|
Rabiu KA, Alausa TG, Akinlusi FM, Davies NO, Shittu KA, Akinola OI. Parental acceptance of human papillomavirus vaccination for adolescent girls in Lagos, Nigeria. J Family Med Prim Care [serial online] 2020 [cited 2021 Jan 16];9:2950-7. Available from: https://www.jfmpc.com/text.asp?2020/9/6/2950/287813
| Introduction|| |
With an estimated 570,000 cases and 311,000 deaths in 2018 worldwide, cervical cancer ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest regional incidences and mortality rates for cervical cancer are seen in Africa.
In Nigeria, cervical cancer is the most common female reproductive tract cancer and is only second to breast cancer as the most common cancer in women the country. In 2018, there were 14,983 new cases representing 21% of all female cancers and 10,403 died from the disease in the country.
Cervical cancer is caused by human papillomavirus (HPV) and HPV 16 and 18 are the high-risk strains, which are responsible for over 70% of cervical cancer.,,, Besides cervical cancer, HPV can also lead to cancer of the vulvar, penis, anus and oropharynx as well as genital warts.
Approved HPV vaccines protect against cervical cancer and are recommended for adolescent girls before sexual debut. Three vaccines that prevent infection with diseases-causing are available: Cervarix, Gardasil, and Gardasil 9. All three vaccines prevent infection with HPV types 16 and 18. Gardasil also prevents infection with HPV types 6 and 11, which causes 90% of genital warts. Gardasil 9 prevents infection with the same four HPV types plus five additional cancer-causing types (31, 33, 45, 52, and 58) that together account for 10%–20% of cervical cancers. Developing countries that have high cervical rates yet lack comprehensive screening may benefit from the vaccines. In Nigeria, only Cervarix and Gardasil are available for the prevention of cervical cancer.
Decision about children's treatment and preventive health care are largely made by their parents. In a study examining perception of the HPV vaccination among female university students in Hong Kong, parents are noted to be decisive in preventing young women from receiving the vaccination.
Acceptance of childhood vaccination by parents is critical. Although HPV vaccination is acceptable to most people surveyed, most acceptability data have emanated from North America and Europe, which may not be applicable elsewhere. There is paucity of data regarding parental acceptance of HPV vaccination in developing countries.
Since the introduction of Cervarix and Gardasil in Nigeria in 2011, the federal government is yet to adopt a national strategy that will ensure equitable access to HPV vaccination. Few studies in the country have assessed parental willingness toward HPV vaccination. No published studies however have used a representative sample of parents from a whole state. This study was therefore carried out to determine factors affecting parental acceptance of HPV vaccination for adolescent secondary-school girls in Lagos State, Nigeria.
We hope that the information obtained will drive public health response most especially at the primary care facilities, which are usually the first facilities visited by patients in the formal health sector and are responsible for implementation of immunization programs in the country. The public health department works with primary care providers at the local government levels to ensure adequate access to vaccines and provision of qualitative preventive health-care services to the community.
| Subjects and Methods|| |
This was a descriptive cross-sectional survey.
The study was carried out in Lagos State, Nigeria with an estimated population of 22,883,047 inhabitants in 2013. The state has 20 local government areas (LGAs) or zones, 12 of which are urban and 8 rural. The state has 328 public junior secondary schools and 313 public senior secondary schools as at 2013 and these and these are fairly evenly distributed across the local governments. The state also has many privately owned junior and senior secondary schools.
The list of all secondary schools in Lagos State was obtained from the ministry of education. The 20 LGAs were divided into the urban group and the rural group. Two LGAs were then chosen from each group by simple random sampling (balloting). A school was then chosen from each of the four chosen LGAs by balloting. In total, two urban and two rural secondary schools were chosen.
The instrument for data collection was a pretested questionnaire put together based on adaptation and literature review on the subject. The questionnaire included questions concerning the sociodemographic characteristics of the respondents, their knowledge of HPV, cervical cancer and HPV vaccines, and their willingness to vaccinate their daughters. The selected schools were visited during the parent–teachers association meetings. The purpose of the study was explained to the parents and those who gave their consent were given the questionnaire to study and fill.
After completing the questionnaire, the respondents were educated about cervical cancer, HPV infection, and its prevention by vaccination and the available vaccines. Confidentiality was maintained by not including their names in the questionnaire in order to elicit the correct responses. The questionnaires were retrieved on the same day.
Data processing and analysis
The authors appraised the responses and categorized the open-ended questions and answers. They were specifically assessed to determine their knowledge of cervical cancer, HPV infection, and HPV vaccination.
The data were entered into the computer and analyzed using the Epi-Info 3.5.3 statistical software of the Centre for Disease Control and Prevention, Atlanta, Georgia, USA to generate descriptive statistics. Crude odds ratio (cOR) and 95% confidence interval (CI) for hypothesized factors affecting willingness of parents to vaccinate their daughters were determined using logistic regression. Variables that were significant at P value <0.05 were then considered for the multivariate logistic regression mode to determine adjusted OR and independent factors determining willingness of parents to vaccinate their daughters.
The Lagos State University Teaching Hospital Research and Ethics Committee gave approval for the study.
| Results|| |
The sociodemographic characteristics of the respondents are shown in [Table 1]. Of the 318 parents surveyed, 20.1% were males and 79.9% were females.
Parental knowledge of cervical cancer and HPV infection is depicted in [Table 2]. Approximately half (45.9%) had poor knowledge of cervical cancer and HPV infection, whereas 78 (24.5%) and 94 (29.6%) had fair and good knowledge, respectively.
[Table 3] assesses the respondent's knowledge of HPV vaccine. The majority (54.7%) had poor knowledge, whereas 18.6% and 26.7% had fair and good knowledge, respectively.
Two hundred and twenty-nine (72%) expressed willingness to vaccinate their daughters if the vaccine were free, whereas 89 (28%) will not vaccinate their daughters even if the vaccines were offered free.
Only 113 (35.5%) of the respondents were willing to vaccinate their daughters if the vaccine comes at a cost, whereas 205 (64.5%) were not willing.
[Table 4] shows univariate analysis of the factors affecting willingness to vaccinate daughters if the vaccine is offered free. Gender of parents, age of parents, educational status of father, occupational status of father, and location of school were not significant factors affecting willingness to vaccinate if free. Tertiary level of education in mother (cOR = 8.31; 95% CI = 3.39–20.38; P= 0.0000), skilled occupational status in the mother (cOR = 8.99; 95% CI = 3.20–25.22; P= 0.0000), good knowledge of cervical cancer and HPV (cOR = 6.14; 95% CI = 2.18–17.27; P= 0.0006) and good knowledge of HPV vaccine (cOR = 3.80; 95% CI = 1.44–10.02; P= 0.0070) significantly increased the likelihood to vaccinate if offered free. Poor Knowledge of cervical cancer and HPV (cOR = 0.44; 95% CI = 0.24–0.81; P= 0.0081) reduced the likelihood if offered free.
|Table 4: Univariate analysis of factors affecting willingness to vaccinate daughters if vaccine is free|
Click here to view
[Table 5] shows the univariate analysis of factors affecting willingness to vaccinate daughters if vaccine is not free. Tertiary level of education in the mother (cOR = 67.41; 95% CI = 15.25–297.97; P= 0.0000), skilled occupation in the mother (cOR = 11.55; 95% CI = 5.55–24.04; P= 0.0000), skilled occupation in the father (cOR = 4.10; 95% CI = 2.31–7.28; P= 0.0000), Urban setting (cOR = 4.48; 95% CI = 2.73–7.37; P= 0.0000), good knowledge of cervical cancer and HPV (cOR = 19.82; 95% CI = 8.99–43.70; P= 0.0000) and gook knowledge of HPV vaccine (cOR = 20.31; 95% CI = 7.18–57.2; P= 0.0000) increased the likelihood for vaccination. Factors that decreased the likelihood of vaccination if the vaccine is not free are poor knowledge of cervical cancer and HPV (cOR = 0.24; 95% CI = 0.11–0.53; P= 0.0000) and poor knowledge of the HPV vaccine (cOR = 0.05; 95% CI = 0.02–1.13; P= 0.0000). After entering the factors significant at a P value of <0.05 into a multiple logistic regression model for multivariate analysis [Table 6], the only factor that remained that remained significant as an independent determinant of willingness to vaccinate when vaccine is free is poor knowledge of cervical cancer and HPV which reduced the likelihood of accepting vaccination by almost half (aOR = 0.47; 95% CI = 0.24–0.94; P= 0.0325). Concerning willingness to vaccinate if the vaccine comes at a cost, tertiary level of education in the mother increased the likelihood about 29 fold (aOR = 29.17; 95% CI = 3.98–214.08; P= 0.0009), whereas good knowledge of HPV vaccine increased the likelihood of acceptance about 6 fold (aOR = 6.11; 95% CI = 1.36–27.43; P= 0.0180). Poor knowledge of HPV vaccine decreased the likelihood of vaccination if the vaccine comes at a cost (aOR = 0.13; 95% CI = 0.03–0.48; P= 0.0022).
|Table 5: Univariate analysis of factors affecting willingness to vaccinate daughters if vaccine is not free|
Click here to view
|Table 6: Multivariate logistic regression analysis of significant factors affecting willingness to vaccinate daughters|
Click here to view
| Discussion|| |
To better understand how HPV vaccination may be implemented in Nigeria, we wanted to investigate parental acceptance toward HPV vaccination and as HPV vaccine was not included in the national vaccination program when the study was conducted, we wanted to explore not only the willingness to vaccinate, but also the willingness to pay for the vaccine.
Nigeria has one of the highest cervical cancer incidences worldwide. A study in Ghana, Nigeria, and South Africa isolated HPV types 16 and 18 in 68.4% of women with invasive cervical cancer suggesting that HPV vaccine could have a large impact.
Many prior effects at cervical cancer screening in Nigeria have largely been ineffective due to limited cytology and treatment services, lack of knowledge about cervical cancer and its screening and implementation and cost barriers. However, successful universal immunization programs do exist using various strategies such as the Expanded Programme for Immunization (EPI). HPV vaccination may thus be a uniquely effective intervention for the prevention of cervical cancer in the country.
Our study revealed that almost half of the participants had poor knowledge of cervical cancer and HPV, its causative agent with only 29.6% showing good knowledge. A study assessing mothers papillomavirus knowledge and willingness to vaccinate their adolescent daughters in Shomolu LGA of Lagos State, Nigeria reported that majority of the mothers were aware of cervical cancer, but only few were aware of HPV and had little knowledge of its link to cervical cancer. This poor knowledge of cervical cancer and its causative agent HPV is not surprising as most previous studies in the country have reported poor knowledge of cervical cancer. Only 25.3% of women attending anti-retroviral clinic in Lagos, Nigeria in 2011 had ever heard of cervical cancer. In 2004, also in Lagos, Nigeria, 81.7% of 139 patients with advanced cervical cancer had never heard of the disease.
A study evaluating HPV vaccine acceptability among women in a semi-urban region of Kisumu, Kenya also reported that only 15% of the women had heard of cervical cancer. In Sakarya Province, Turkey, 88.1% of mothers had no information about HPV and 73.3% did not know how the infection was transmitted. A recent study assessing parental knowledge and perception of HPV and cervical cancer prevention in Rural Central Java, Indonesia also reported that most parents had no knowledge of HPV or the causal link between HPV and cervical cancer.
Our study also showed that most of the respondents had poor knowledge of the HPV vaccine. Most studies from developing countries also showed poor knowledge of HPV vaccines among parents.,,
In Nigeria, the HPV vaccine was launched and inaugurated by the federal government in 2011 and since then, has been administered by private facilities. The relatively poor knowledge of the vaccine in Nigeria since its inauguration shows that little has been carried out to create awareness about it and much work is needed in this area. Awareness can be created with the development of health promotion and educational strategies for the public especially through the primary health care facilities which are closer to the people in the community. Considering the high burden of cervical cancer in Nigeria, creating awareness on HPV vaccination will be a step in the right direction. Successful education of the general populace will require continued education about the preventable nature of cervical cancer, the need for continued screening despite vaccination, cost of vaccines and details of vaccine efficacy and its effects.
Despite the poor knowledge of cervical cancer, HPV, and HPV vaccine, 72% of the parents were willing to vaccinate their daughters if the vaccine is offered free. This figure is less than those reported in some local studies. In Shomolu local government in Lagos, Nigeria, 88.9% of mothers were willing to vaccinate their adolescent daughters, whereas 88.6% of reproductive aged women in Ibadan, Southwestern Nigeria were willing to vaccinate their daughters., A recent study from Abakaliki South-eastern Nigeria also reported that 89.1% of mothers were willing to vaccinate their adolescent daughters. It is however worthy of note that higher acceptance rates were reported in some other African countries. A much higher rate of 94% was reported from Ghana, whereas 95% was reported from Kenya., The observed difference may not be unconnected with the fact that these countries have better routine immunization coverage rates than Nigeria according to the Global Alliance for Vaccines and Immunization (GAVI) assessment indicators. The 2011 World Health Organization/UNICEF estimates for Diphtheria, Pertusis, and Tetanus-3 (DPT3) vaccination coverage showed that Ghana had a national coverage of 91%, whereas Kenya had a coverage of 88%. The reported coverage for Nigeria was 66%.
It is imperative to note that that only 35.5% of the parents were willing to vaccinate their daughters if the vaccine came at a cost. This finding is similar to what was reported in Kenya, another developing country where only 25% of the parents were willing to pay more than 1.32 US dollar for the complete series. In Sweden, up to 63% of parents were willing to vaccinate their Children even if the vaccine comes at a cost. Also, in rural Central Java, Indonesia, most parents were supportive of vaccinating their children against HPV even at a fee. This lack of willingness of most parents in Lagos, Nigeria to pay for the vaccine highlights the importance of international agencies in assisting with the cost of HPV vaccine in developing countries so that if possible, the vaccine can be offered free because sustaining free HPV vaccination by the governments might be a difficult policy to implement due to competing health challenges.
Recently, the GAVI Alliance has offered a subsidy for developing countries that meets its eligibility criteria. The GAVI Alliance uses two criteria to determine eligibility for vaccination support, including HPV vaccination: (1) a DPT3 threshold of 70% national coverage and (2) a pilot demonstration of the ability to deliver a complete multi-dose series of vaccines to at least 50% of the target vaccination cohort in an average sized district in a county. Nigeria does not meet the DPT3 threshold of 70% national coverage. It is therefore important that policy makers and stake holders come together to fashion out feasible and sustainable policy to fund the vaccination program in the country.
Our study went on to explore factors influencing willingness of parents to vaccinate their daughters if the vaccine is offered free and also when it comes at a cost. Most previous studies did not investigate association between cervical cancer and HPV knowledge and parental acceptance for HPV vaccination. Our study however showed that knowledge of cervical cancer and HPV is a significant correlate for HPV vaccine acceptance with poor knowledge reducing the probability of vaccine acceptance by almost 50%. Also, in Ibadan, South West Nigeria, knowing that cervical cancer is preventable is significantly associated with willingness to allow HPV vaccination to children.
Our study also revealed that tertiary level of education in the mother increased the probability of vaccine acceptance almost 30-fold. It is likely that these women with tertiary level of education have better knowledge of cervical cancer and its prevention than those who are less well educated. A study in Israel showed that the more aware an individual is about the dangers in contracting HPV, the higher the interest shown in preventive measures.
Several studies have also shown that parents who knew that vaccination was a safe and effective way to prevent disease were more likely to vaccinate their children against HPV., It was therefore not surprising that this study showed that parents who had good knowledge of HPV vaccine were more likely to vaccinate their daughters even when they have to pay for it, whereas poor knowledge decreased the probability.
The study was limited by the fact that there might have been some recall bias in answering some of the questions by the respondents. The study however showed that HPV vaccination for adolescent secondary school girls was acceptable to most parents in Lagos, Nigeria only if offered free as majority were not willing to pay for the vaccine and this is not likely to be different in other parts of the country.
Poor knowledge of cervical cancer, HPV infection and HPV vaccines may hinder acceptability. Educational programs to improve parental knowledge are required. It is imperative that policy makers and stake holders in the country come together to fashion out feasible and sustainable policy to fund HPV vaccination in the country so that it can be incorporated free into the National Programme on Immunization.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bray F, Ferley J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global Cancer Statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
Tristam A, Finander A. Human papillomavirus (including vaccines). Obstet Gynaecol Reprod Med 2007;17:324-9.
Walboomers JMM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, et al.
Human papillary virus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-9.
Lowly DR, Schiller JT. Reducing HPV associated cancer globally. Cancer Prev Res (Phila) 2012;5:18-23.
Waheed MT, Gottschamel J, Hassan SW, Lossi AG. Plant-derived vaccines: An approach for affordable vaccines against cervical cancer. Hum Vaccines Immunother 2012;8:403-6.
Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human papillomavirus vaccination for adults: Updated recommendations of the Advisory Committee on Immunization Practice. MMWR Morb Mortal Wkly Rep 2019;68:698-702.
Bello FA, Enabor OO, Adewole IF. Human papilloma virus vaccination for control of cervical cancer: A challenge for developing countries. Afr J Reprod Health 2011;15:25-30.
Siu JY. Perceptions of barrier to vaccinating daughter sagainst human papillomavirus (HPV) among mothers in Hong Kong. BMC Womens Health 2014;14:73.
Brewer NT, Fazekas KI. Predictors of HPV vaccine acceptability: A theory-informed systematic review. Prev Med 2007;45:107-14.
Jedy-Agba E, Curado MP, Ogunbiyi O, Oga E, Fabowale T, Igbinoba F, et al.
Cancer incidence in Nigeria: A report from population-based cancer registries. Cancer Epidemiol 2012;36:e271-8.
Denny L, Adewole I, Anorlu R, Dreyer G, Moodley M, Smith T, et al.
Human papillomavirus prevalence and type distribution in invasive cervical cancer in sub-saharan Africa. Int J Cancer 2014;134:1389-98.
Ezenwa BN, Balogun MR, Okafor JP. Mothers human papilloma virus knowledge and willingness to vaccinate their adolescent daughters in Lagos, Nigeria. Int J Womens Health 2013;5:371-7.
Rabiu KA, Akinbami AA, Adewunmi AA, Akinola OI, Wright KO. The need to incorporate routine cervical cancer counselling and screening in the management of HIV positive patient in Nigeria. Asian Pac J Cancer Prev 2011;12:1211-4.
Anorlu RI, Orakwue CO, Oyeneyin L. Abudu OO. Late presentation of patients with cervical cancer to a tertiary hospital in Lagos: What is responsible? Eur J Gynaecol Oncol 2004;25:729-32.
Becker-Dreps S, Otieno WA, Brewer NT, Agot K, Smith JS. HPV vaccine acceptability among Kenyan women. Vaccine 2010;28:4864-7.
Kose D, Erkorkmaz U, Cinar N, Altinkaynak S. Mothers knowledge and attitude about HPV vaccination to prevent cervical cancer. Asian Pac J Cancer Prev 2014;15:7236-66.
Spagnoletti BRM, Bennett LR, Wahdi AE, Wilopo SA, Keenan CA. A qualitative study of parental knowledge and perceptions of human papillomavirus and cervical cancer prevention in rural central Java, Indonesia: Understanding community readiness for prevention intervensions. Asian Pac J Cancer Prev 2019;20:2429-34.
Morhason-Bello IO, Wallis S, Adedokun BO, Adewole IF. Willingness of reproductive-aged women in a Nigerian community to accept human papillomavirus vaccination for their children. J Obstet Gynaecol Res 2015;41:1621-9.
Azuogu BN, Umeokonkwo CD, Azuogu VC, Onwe OE, Okedo-Alex IN, Egbuji CC. Appraisal of willingness to vaccinate daughters with human papilloma virus vaccine and cervical cancer screening uptake among mothers of adolescent students in Abakaliki, Nigeria. Niger J Clin Pract 2019;22:1286-91.
] [Full text]
Coleman MA, Levison J, Sangi-Haghpeyker H. HPV vaccine acceptability in Ghana, West Africa. Vaccine 2011;29:3945-50.
Perlman S, Wamai RG, Bain PA, Welty T, Welty E, Ogembo JG. Knowledge and awareness of HPaccine and acceptability to vaccinate in sub-Saharan Africa: A systematic review. PLoS One 2014;9:e90912.
Dahlstrom LA, Tran TN, Lundholm C, Young C, Sundstrom K, Sparen P. Attitudes to HPV vaccination among parents of children aged 12-15 years- A population based survey in Sweden. Int J Cancer 2010;126:500-7.
GAVI injects new life into HPV vaccine rollout. Lancet 2013;381:1688.
Wigle J, Coast E, Watson-Jones D. Human papillomavirus (HPV) vaccine implementation in low and middle income countries (LMICs): Health system experiences and prospects. Vaccine 2013;31:3811-7.
Ben Natan M, Aharon O, Palickshvili S, Gurman V. Attitude of Israeli mothers with vaccination of their daughters against human papilloma virus. J Paediatr Nurs 2011;26:70-7.
Marlow LA, Waller J, Wardle J. Parental attitudes to pre-pubertal HPV vaccination. Vaccine 2007;25:1945-52.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]