Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Human papillomavirus prevalence and type distribution among women attending routine gynecological examinations in Saudi Arabia

  • Abdulaziz AlObaid1,
  • Ismail A Al-Badawi2Email author,
  • Hanan Al-Kadri3,
  • Kusuma Gopala4,
  • Walid Kandeil5,
  • Wim Quint6,
  • Murad Al-Aker2, 7 and
  • Rodrigo DeAntonio5
BMC Infectious Diseases201414:643

https://doi.org/10.1186/s12879-014-0643-8

Received: 22 April 2014

Accepted: 19 November 2014

Published: 14 December 2014

Abstract

Background

Cervical cancer (CC) is caused by persistent infection with high-risk (HR) human papillomavirus (HPV) types. In Saudi Arabia which has a population of 6.5 million women over the age of 15 years, approximately 152 new cases of CC are diagnosed and 55 women die from the disease annually. Nevertheless current epidemiological data for HPV in this population are limited. This study evaluated the prevalence and type distribution of HPV and documented the awareness of HPV infection and health-related behavior among Saudi and non-Saudi women attending routine examination.

Methods

This was an observational, epidemiological cross-sectional study conducted between April 2010 and December 2011 at three hospitals in Saudi Arabia. Cervical samples from women aged ≥15 years, who were attending routine gynecological examinations were collected and tested for HPV-DNA by polymerase chain reaction and typed using the SPF10 DEIA/LiPA25 system. Two questionnaires on health-related behavior and awareness of HPV infection were completed.

Results

A total of 417 women, mean age (standard deviation) 41.9 (±10.4) years, were included in the final analysis, of whom 77% (321/417) were Saudi nationals. HPV-DNA was detected in 9.8% women (41/417, 95% confidence interval [CI]: 7.1-13.1). The prevalence of any HR-HPV by age was: 25–34 years: 3.0%; 35–44 years: 4.5%; 45–54 years: 3.2%; >55 years: 10.9%. The most prevalent HR-HPV-types were: HPV-68/73 (5 cases); HPV-18 (4 cases); HPV-16 (3 cases). The most prevalent low risk (LR) types were HPV-6 (4 cases); HPV-42, HPV-53 and HPV-54 (2 cases each). The prevalence of HPV was higher among non-Saudi nationals vs. Saudi nationals (16.7% vs. 7.8%, P = 0.0234). No statistically significant risk factors were identified: 32.2% (101/314) women were aware of HPV and 89.9% (285/317) showed an interest in HPV vaccination.

Conclusion

The overall prevalence of HPV was 9.8% in Saudi Arabia, but was higher in women over 55 years, as well as in non-Saudi nationals. These data provide a reference for public health authorities and may also help in determining future policies for the prevention of CC.

Clinical trial registration

NCT01213459

Keywords

Human papillomavirus Saudi Arabia Epidemiology

Background

Cervical cancer (CC) is the third most frequent cancer in women throughout the world and was associated with an estimated 530,000 new cases and 275,000 deaths in 2008 [1]. The global age standardized incidence rate for CC is 15.2 per 100,000 population [2]. Saudi Arabia has a population of 6.5 million women over the age of 15 years [3]. Based on the available data, around 152 women are diagnosed with CC and 55 die from the disease annually, corresponding to the 11th most frequent cancer among women of all ages in this population [3]. However, as not all CC cases are reported in Saudi Arabia, there is a concern that the real incidence of CC may be somewhat higher.

It is known that CC is caused by persistent infection with high-risk (HR) human papillomavirus (HPV) types [4],[5], of which HPV-16 and HPV-18 are responsible for approximately 70% of the overall cases [6]. Two HPV vaccines are currently licensed in many countries: a bivalent vaccine (Cervarix®, GlaxoSmithKline, Belgium) and a quadrivalent vaccine (Gardasil®, Merck and Co., Inc., Whitehouse Station, New Jersey), both of which are well-tolerated and have good efficacy profiles [7]-[14]. The introduction of these vaccines provides an opportunity to reduce CC, but the introduction of such a preventive measure, requires baseline data on national epidemiology and prevalent circulating HPV strains.

The epidemiology of HPV amongst women in Saudi Arabia is not fully understood and only limited publications about the prevalence, detection and genotyping of HPV [15]-[17] and attitudes towards screening are available in this population [18],[19]. In order to bridge this gap and provide baseline data, this study was undertaken to evaluate the prevalence and type distribution of HPV, including HR and low risk (LR)-types, among Saudi and non-Saudi women. The study also documented the level of awareness of HPV infection, health-related behavior, and potential risk factors for HPV infection among women attending routine gynecological screening.

Methods

Study design and study population

This multicenter, observational, cross-sectional, epidemiological study (NCT01213459) was conducted between April 2010 and December 2011 at three large hospitals: King Fahd Medical City (KFMC), King Faisal Specialist Hospital and Research Centre (KFSH and RC) and King Abdulaziz Medical City-National Guard Health Affairs (KAMC-NGHA) in Riyadh, Saudi Arabia. Women aged ≥15 years undergoing routine gynecological examination and willing to provide a cervical sample were enrolled. Pregnant women above 25 years or women with a known diagnosis of immunosuppression, or those who had undergone hysterectomy were excluded from the study. Cytological examination of the collected cervical samples was undertaken locally in the laboratories at each hospital. The investigator issued two questionnaires for completion by all women; these assessed health-related behavior and their awareness of HPV. The responses to these questionnaires were anonymous and confidentiality was maintained.

Sample collection and laboratory procedures

Endocervical samples were also collected during the first visit by a trained practitioner/gynecologist using a cytobrush and placed in a liquid-based cytology transport medium (PreservCyt®, ThinPrep Pap Test; Cytyc Corporation, Boxborough, Massachusetts). Samples were stored at room temperature at the sites for four weeks and then at −20°C until shipment to the DDL Diagnostic Laboratory (Rijswijk, The Netherlands).

DNA was isolated from 500 μl of the cervix-vagina on a MagNA Pure Robot (Roche Diagnostics, Almere, The Netherlands) using the MagNA Pure LC Total NAILV kit and eluted in 50 μl of elution buffer [20]. Samples were tested for HPV-DNA at DDL by broad-spectrum polymerase chain reaction (PCR) using HPV short PCR fragment 10 (SPF-10) and PCR DNA enzyme immunoassay (PCR-DEIA) to amplify and recognize at least 57 HPV genotypes by hybridization with a cocktail of nine conservative probes. If positive by SPF10-DEIA the amplimers were further analyzed by Line probe assay 25 (LiPA25) version 1 system (Labo Biomedical Products, Rijswijk, The Netherlands). This Line probe assay 25 (LiPA25) version 1 system (Labo Biomedical Products, Rijswijk, The Netherlands) was used to genotype 25 HR and LR HPV types [21]. (The sequence variation within the SPF10 inter-primer region did not allow HPV type 68 and 73 to be distinguished [22],[23]). DEIA positive-LiPA negative samples were denoted as non-typeable.

Sample size calculation

The primary objective of the study was to describe the prevalence and types of HPV (including multiple infections) among women ≥15 years of age. To meet this objective, an estimated HPV prevalence ranging from 10 to 30% as previously reported [17],[24],[25], was considered. Given a precision level of 0.045, the required number of subjects ranged from 188 subjects for a 10% HPV prevalence to 450 subjects for a 30% prevalence, including an assumption of 10% of subjects non-evaluable.

Statistical analyses

The percentage of women in each category who were HPV positive was tabulated with corresponding 95% confidence intervals (CI). Descriptive analyses regarding HPV prevalence, HPV-types, age distribution, potential risk factors (education level, life-time marital partners, parity and smoking status) and HPV status were performed. An exploratory analysis was performed to assess the association between the HPV status and nationality (two sided Fisher’s exact test) and the adjusted odds ratio (adjusted for factors which are associated with the risk of HPV infection) was calculated using multivariate logistic regression model. All statistical analyses were performed using the statistical analysis software (SAS®) version 9.2.

Ethical considerations

The study was approved by the following local ethics review bodies: Institutional Review Board at KAMC-NGHA; Institutional Review Board at KFMC; Research Ethics Committee of Office of Research Affairs at KFSH and RC. The study was conducted in accordance with the Declaration of Helsinki, good clinical practice guidelines and local rules and regulations of the country. A written informed consent was obtained from all eligible women before entering the study. The investigator communicated results as appropriate to the subjects, including the need for additional testing or treatment.

Results

Study population

Of 420 enrolled women, 417 were included in the final analysis (three were excluded: two due to pregnancy and one due to hysterectomy). A total of 151, 152 and 117 women were enrolled at the KFMC, KFSH and RC, and KAMC-NGHA hospitals, respectively. Overall, 319 women completed the health-related behavior questionnaire and 317 completed the HPV awareness questionnaire. The mean age (standard deviation) of the population was 41.9 (±10.45) years and 77% (321/417) were Saudi nationals. Most women (93.1%, 297/319) were married and 63.0% (201/319) had studied up to post-secondary/university level.

Overall HPV prevalence and type distribution

HPV-DNA was detected in 41 out of 417 women (9.8%), of whom 25 had single HPV-type infection, 4 had multiple HPV-type infection and at least12 women were infected with non-typeable HPV-types. Overall, the most prevalent HR-HPV-types were HPV-68/73 (5 cases); HPV-18 (4 cases); HPV-16 (3 cases) and the most prevalent LR types were HPV-6 (4 cases); HPV-42, HPV-53 and HPV-54 (2 cases each) (Table 1).
Table 1

HPV prevalence and type distribution (N = 417)

N = 417

n

%

95% CI

HPV negative

376

90.2

86.9–92.9

HPV positive

41

9.8

7.1–13.1

Single infection

25

61.0

44.5–75.8

Multiple infection

4

9.8

2.7–23.1

Non-typeable#

12

29.3

16.1–45.5

HPV-types (n = 41)*

Any high-risk HPV**

18

43.9

28.5–60.3

HPV-68/73

5

12.2

4.1–26.2

HPV-18

4

9.8

2.7–23.1

HPV-16

3

7.3

1.5–19.9

HPV-31

2

4.9

0.6–16.5

HPV-51

2

4.9

0.6–16.5

HPV-52

2

4.9

0.6–16.5

HPV-39

1

2.4

0.1–12.9

HPV-56

1

2.4

0.1–12.9

HPV-58

1

2.4

0.1–12.9

Any low-risk HPV***

14

34.1

20.1–50.6

HPV-6

4

9.8

2.7–23.1

HPV-42

2

4.9

0.6–16.5

HPV-53

2

4.9

0.6–16.5

HPV-54

2

4.9

0.6–16.5

HPV-11

1

2.4

0.1–12.9

HPV-40

1

2.4

0.1–12.9

HPV-70

1

2.4

0.1–12.9

HPV-74

1

2.4

0.1–12.9

N: number of women whose cervical samples were tested; n: number of women in a given category; 95% CI: exact 95% confidence interval.

#DEIA positive-LiPA negative.

*Some women were infected with multiple HR/LR HPV types.

**Includes 14 women with single HR-HPV infection and 4 women with multiple infections and at least one HR-HPV type.

***Includes 11 women with single LR-HPV infection and 3 women with multiple infections and at least one LR-HPV type.

Note: Single infection = 25/417 = 6.0% (95% CI: 3.9–8.7); Multiple infection = 4/417 = 0.9% (95% CI: 0.3–2.4); non-typeable = 12/417 = 2.9% (95% CI: 1.5–5.0).

HPV prevalence and type distribution by age

The prevalence of any HR-HPV was highest (10.9%) among women over 55 years; LR-HPV-types were also found in 6.5% of this age group (Figure 1). However, no statistical significance was noted by age group.
Figure 1

HPV prevalence and type distribution by age (N = 417*). *Note: For 2 women, dates were not available; hence age could not be estimated. Note: The error bars represent 95% confidence intervals.

HPV prevalence and type distribution by nationality

The prevalence of HPV was higher (16.7% vs. 7.8%, P = 0.0234) among non-Saudi nationals (n = 96) as compared with Saudi nationals (n = 321) respectively (Figure 2).
Figure 2

HPV prevalence and type distribution by nationality (N = 417). Note: The error bars represent 95% confidence intervals.

HPV co-infection

Multiple infections were observed in four women; three of whom were infected with HR-HPV-68/73 (−68/73 with −52, −39, −53; −68/73 with −40; and −68/73 with −54). One woman had a co-infection of HR-HPV-16 with −31. No HR-HPV-18 positive women were co-infected with any other HR-HPV-types.

Awareness and health related behavior questionnaire results

The potential risk factors of educational level, number of life-time partners, parity and smoking status assessed using univariate analyses showed no statistical associations with any HPV infection (Table 2). Of 317 women completing the HPV awareness questionnaire, 101 (32.2%) were aware of HPV and 285 (89.9%) expressed an interest in vaccination (Table 3).
Table 2

Prevalence of any HPV by risk factors (N = 319)

Risk factors

Categories

N

HPV+

%

Adj. OR

LL–UL

P value

Age at sample collection (years)

<30*

56

3

5.36

.

.

.

30-39

124

12

9.68

3.310

0.391–28.052

0.2723

40-49

132

12

9.09

2.097

0.230–19.085

0.5110

50-60

89

12

13.48

4.136

0.454–37.681

0.2079

>60

14

2

14.29

9.570

0.601–152.366

0.1097

Nationality

Non-Saudi*

96

16

16.67

.

.

.

Saudi

321

25

7.79

0.315

0.116–0.855

0.0234

Education level

No formal education*

21

2

9.52

.

.

.

Primary

47

3

6.38

1.039

0.144–7.489

0.9693

Secondary

50

4

8.00

1.515

0.200–11.492

0.6879

Post-secondary/University

201

24

11.94

1.158

0.180–7.447

0.8770

Number of marital partners

1*

286

29

10.14

.

.

.

2-5

32

4

12.50

1.129

0.324–3.941

0.8488

Parity

0*

8

0

0.00

.

.

.

1-2

100

11

11.00

>999.999

<0.001– > 999.999

0.9516

3-5

112

14

12.50

>999.999

<0.001– > 999.999

0.9502

≥ 6

71

5

7.04

>999.999

<0.001– > 999.999

0.9518

Smoking status

No*

273

30

10.99

.

.

.

Yes

44

3

6.82

0.502

0.134–1.875

0.3053

N: number of subjects in a given cohort; %: HPV+/number of subjects with available results × 100; Adj. OR: Adjusted odds ration from simple logistic regression model Odds ratio adjusted for the other variables; 95% CI: Wald 95% confidence interval; LL: lower limit; UL: upper limit.

*Reference category.

Table 3

Awareness of HPV infection among women (N = 317)

Characteristics

Categories

n

%

How common is cervical cancer in women?

Very common

48

15.1

Common

157

49.5

Rare

56

17.7

Not sure

56

17.7

What do you think is/are the main reasons for cervical cancer?*

It develops from inside

95

30.0

Bacterial infection

49

15.5

Viral infection

80

25.2

None

14

4.4

Not sure

85

26.8

Which among these can cause cervical cancer?*

Persistent infection with HPV

82

25.9

Rous sarcoma virus

23

7.3

Hereditary/genetic factors

115

36.3

None

18

5.7

Not sure

88

27.8

What do you think can turn in to cervical cancer*

Genital warts

109

34.4

Bacterial infection

56

17.7

Fungal infection

26

8.2

None

23

7.3

Not sure

108

34.1

Apart from avoiding unwanted pregnancy, what would you think can happen with using contraceptive pills*

Protects against cervical cancer

31

9.8

Increases risk of cervical cancer

123

38.8

No ill effect at all

77

24.3

Not sure

86

27.1

Did you hear about HPV before?

Yes

101

32.2

No

213

67.8

Missing

3

-

If yes*,

General physician

28

8.8

Friend or family member

20

6.3

Internet

22

6.9

TV/Magazine/Newspaper

46

14.5

Other

14

4.4

How is HPV transmitted?*

Contaminated food/Water

10

3.2

Mosquito bite

3

0.9

Sexually

159

50.2

None

20

6.3

Not sure

127

40.1

How is cervical cancer diagnosed?*

Pap smear test

77

24.3

Colposcopy

24

7.6

Biopsy sample testing (histological)

122

38.5

All above

82

25.9

None

2

0.6

Not sure

30

9.5

Is it possible to prevent cancer?

Yes

243

78.9

No

26

8.4

Not sure

39

12.7

Missing

9

-

If yes*,

Through cancer vaccine

58

18.3

Through responsible sexual behavior

46

14.5

Through cervical screening

173

54.6

Through condom use

14

4.4

If the vaccine against cervical cancer is available, would you be interested in getting vaccinated?

Yes

285

89.9

No

32

10.1

N: number of women in a specified category for whom questionnaire data were collected.

*Women could have selected more than one option.

Discussion

This study estimated the prevalence and type distribution of HPV in 417 women above 15 years of age attending routine gynecological screening at three large hospitals in Riyadh, Saudi Arabia. We reported a 9.8% prevalence for HPV, which is much lower than the 31.6% overall prevalence of HPV-16/18 reported previously in a small study involving subjects from Riyadh [24]. An earlier report from Jeddah reported a 5.6% prevalence of HR-types [17]. These differences could be due to many factors including differences in HPV testing technology, study size, age groups or geographical variations. The study which was undertaken in Riyadh [24] included a limited number of subjects (75 Saudi nationals and 45 from other countries) from just one hospital (which was also included in our study). The higher proportion of non-Saudi nationals in this study might help to explain the observed higher HPV prevalence [24]. Conversely, although the sample size in the study conducted in Jeddah [17] was similar to that in our present study, the exclusion of non-Saudi nationals might explain the lower reported HPV prevalence. According to available data, our study included a representative number of Saudi and non-Saudi nationals, which reflects the current demography of Saudi Arabia [25]. This might explain higher HPV prevalence in our study compared to the Jeddah study. Our study might therefore be more representative of the current situation in Saudi Arabia given the larger sample size as well as the inclusion of non-Saudi nationals.

Indeed, data from the Saudi Cancer registry suggest that there are regional differences in the percentage distribution of CC with the northern region having the highest (6.4%) percentage distribution compared with the other regions [26].

According to the United Nations classification, Saudi Arabia belongs to the Western Asia region [27], which has a lower HPV prevalence rate (2.2% [95% CI, 1.5–3.1]) compared with global rates (11.4% [95% CI, 11.3–11.5]) in women with normal cytology [2]. The crude incidence rate of CC per 100,000 women per year in Saudi Arabia is 1.3, which is lower than that in Western Asia (3.6) and the world (15.8) [2]. The prevalence of HPV in women with CC in Saudi Arabia has a broad range (43–89%) [28],[29] compared with the global prevalence (85–99%) [6]. The low rates of CC in Saudi Arabia as compared with other countries could be due to differences in sexual practices and attitudes. For example, the population in Saudi Arabia is more conservative than western countries where most of the data derive [30]. The exact reasons for these low rates in Saudi Arabia are not known, but highlight the need for recent data to better understand the disease burden of HPV and the prevalent circulating types.

The most prevalent HR-HPV-types reported in our study were HPV-68/73, 18 and 16; the most common LR-HPV-types were HPV-6, 42, 53 and 54. HPV-types 16 and 18 have been predominantly reported in HPV infections globally and the results of our study were therefore consistent [24],[31]. We did however note a high prevalence of HPV-68/73 for the first time, especially among non-Saudi nationals. HPV-68 type has been reported throughout the world, with the exception of North America, albeit at a lower prevalence [32]. However, our results should be considered with caution as only five women were positive for HPV-68/73. Future studies to substantiate this finding are therefore indicated.

Our study also found that HR-HPV infection was highest (10.9%) in the oldest age group (>55 years). These results are consistent with the general worldwide trend of higher HPV burden in older women. However, the comparator study from Bruni et al. [31] only included women with normal cytology whereas the cytology status was not known in the present study [32].

We estimated a higher proportion of infection in non-Saudi nationals compared with the Saudi nationals. This difference could be due to many reasons including different cultural behaviors such as male circumcision [32],[33], sexual behavior or prevalence in the native countries. Further studies are therefore warranted. Although, it appears that non-Saudi nationals are at a greater risk of contracting infection, prevalent HPV types indeed pose a risk of infecting Saudi nationals. Our study did not find educational level, number of lifetime partners, parity or smoking status to be significantly associated risk factors for HPV-16, HPV-18 or any HR-HPV infection.

Our study results should be interpreted with caution as the study design was cross sectional, i.e., we obtained single point estimates of women with HPV infections. These infections could have been transient and resolved on their own rather than leading to CC. In addition, since the overall number of women positive for HPV itself was low, the prevalence of HPV types should be interpreted with caution. Another limitation lies within the recruitment process: women with higher levels of education are more likely to opt for cervical cancer screening and therefore would be more likely to participate in our study. Nevertheless, our study did also include women who did not have formal education.

A major strength of this study was the high quality of HPV-DNA testing across the three hospitals in all age groups which helps to provide a representative sample of the population. The study also met the required sample size to calculate an overall prevalence of 9.8% with good precision. Furthermore, the questionnaires were completed by most enrolled women giving an important insight into behavior and attitudes, and suggesting that the introduction of a preventive measure such as vaccination would be accepted. Reports indicate that the proportion of non-Saudi nationals represent 20%–30% of the entire population in Saudi Arabia [25],[34] which is consistent with our results (23%). In addition, the proportion of women completing up to post-secondary/university level education in our study (63%) is comparable to the Organization for Economic Co-operation and Development (OECD) reports, where at least 50% of women were educated and at least 54% of women among all OECD countries completed post-secondary education [35]. These comparisons therefore indicate the representativeness of our study population.

The study results emphasize the need for a future updated policy for HPV and CC prevention in Saudi Arabia. A World Health Organization document on cancer control in the Eastern Mediterranean region describes that only 35% of CC cases present at early stage; as in other developing countries, the rest are reported at later stages when cure is unlikely, even with the best treatment [34]. It has also been reported that when women are double negative in the conventional cytological screening test and the highly sensitive HPV molecular test, then screening can be performed at longer intervals [36]. Our study findings together with these data will help determine the best strategy for targeting preventive interventions, and designing public health measures for Saudi Arabia.

Conclusion

The overall results from this study emphasize that the HPV burden in Saudi Arabia is a cause for concern and preventive strategies such as screening, HPV-DNA testing of cervical samples and vaccination might reduce the burden of the disease. Our data can raise the awareness of local authorities and public health officials and help to guide policy in Saudi Arabia to implement strategies to prevent CC.

Trademark

Cervarix is a trademark of the GlaxoSmithKline group of companies

Gardasil is a trademark of Merck & Co. Inc.

PreservCyt is a trademark of Cytyc Corporation, Massachusetts, United States of America

Labo Biomedical Products, Rijswijk, The Netherlands

Abbreviations

CC: 

Cervical cancer

CI: 

Confidence interval

DEIA: 

DNA enzyme immunoassay

HPV: 

Human papillomavirus

HR: 

High-risk

KAMC-NGHA: 

King Abdulaziz Medical City-National Guard Health Affairs

KFMC: 

King Fahd Medical City

KFSH and RC: 

King Faisal Specialist Hospital and Research Centre

LiPA25: 

Line probe assay 25

LR: 

Low-risk

OECD: 

Organization for Economic Co-operation and Development

PCR: 

Polymerase chain reaction

SAS: 

Statistical analysis software

SPF-10: 

Short PCR fragment 10

Declarations

Acknowledgements

The authors would like to thank Dr. Mamoun ElAwad for his participation in the conduct of the study, Karin Hallez and Mohammed Bassyouni for monitoring the study sites (both employed by GlaxoSmithKline group of companies). The authors also thank Shruti Priya Bapna, Harshith Bhat and Preethi Govindarajan (all employed by GlaxoSmithKline group of companies) for preparation of the manuscript, Julia Donnelly (on behalf of GlaxoSmithKline Vaccines) for language editing and Abdelilah Ibrahimi (XPE Pharma and Science on behalf of GlaxoSmithKline Vaccines) for publication coordination.

Funding source

GlaxoSmithKline Biologicals SA sponsored and funded the study conduct, analyses of data and the development and publication of the manuscript.

Authors’ Affiliations

(1)
King Fahd Medical City
(2)
King Faisal Specialist Hospital & Research Centre
(3)
Department of Obstetrics and Gynecology, King Abdulaziz Medical City, College of Medicine, King Saud bin Abdulaziz University for Health Sciences
(4)
GlaxoSmithKline Pharmaceuticals Ltd
(5)
GlaxoSmithKline Vaccines
(6)
DDL Diagnostic Laboratory
(7)
Sydney Gynecologic Oncology Group, Royal Prince Alfred Hospital

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010, 127 (12): 2893-2917. 10.1002/ijc.25516.View ArticlePubMedGoogle Scholar
  2. Rana MM, Huhtala H, Apter D, Eriksson T, Luostarinen T, Natunen K, Paavonen J, Pukkala E, Lehtinen M: Understanding long-term protection of human papillomavirus vaccination against cervical carcinoma: Cancer registry-based follow-up. Int J Cancer. 2013, 132 (12): 2833-2838. 10.1002/ijc.27971.View ArticlePubMedGoogle Scholar
  3. WHO/ICO Information Centre on HPV and CC Human Papillomavirus and Related Cancers in Saudi Arabia. [http://www.who.int/immunization/topics/hpv/en/]. Last accessed: 06 Jan 2014.
  4. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999, 189 (1): 12-19. 10.1002/(SICI)1096-9896(199909)189:1<12::AID-PATH431>3.0.CO;2-F.View ArticlePubMedGoogle Scholar
  5. Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ, International Agency for Research on Cancer Multicenter Cervical Cancer Study G: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med. 2003, 348 (6): 518-527. 10.1056/NEJMoa021641.View ArticlePubMedGoogle Scholar
  6. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, Tous S, Felix A, Bravo LE, Shin HR, Vallejos CS, de Ruiz PA, Lima MA, Guimera N, Clavero O, Alejo M, Llombart-Bosch A, Cheng-Yang C, Tatti SA, Kasamatsu E, Iljazovic E, Odida M, Prado R, Seoud M, Grce M, Usubutun A, Jain A, Suarez GA, Lombardi LE, Banjo A, et al: Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010, 11 (11): 1048-1056. 10.1016/S1470-2045(10)70230-8.View ArticlePubMedGoogle Scholar
  7. Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G: Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009, 5 (5): 332-340. 10.4161/hv.5.5.7211.View ArticlePubMedGoogle Scholar
  8. Paavonen J, Naud P, Salmeron J, Wheeler CM, Chow SN, Apter D, Kitchener H, Castellsague X, Teixeira JC, Skinner SR, Hedrick J, Jaisamrarn U, Limson G, Garland S, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Jenkins D, Hardt K, Zahaf T, Descamps D, Struyf F, Lehtinen M, Dubin G, Group HPS: Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women. Lancet. 2009, 374 (9686): 301-314. 10.1016/S0140-6736(09)61248-4.View ArticlePubMedGoogle Scholar
  9. Einstein MH, Baron M, Levin MJ, Chatterjee A, Fox B, Scholar S, Rosen J, Chakhtoura N, Meric D, Dessy FJ, Datta SK, Descamps D, Dubin G, Group HPVS: Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine: follow-up from months 12–24 in a Phase III randomized study of healthy women aged 18–45 years. Hum Vaccin. 2011, 7 (12): 1343-1358. 10.4161/hv.7.12.18281.View ArticlePubMedPubMed CentralGoogle Scholar
  10. Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T: Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008, 26 (51): 6630-6638. 10.1016/j.vaccine.2008.09.049.View ArticlePubMedGoogle Scholar
  11. Castellsague X, Munoz N, Pitisuttithum P, Ferris D, Monsonego J, Ault K, Luna J, Myers E, Mallary S, Bautista OM, Bryan J, Vuocolo S, Haupt RM, Saah A: End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24–45 years of age. Br J Cancer. 2011, 105 (1): 28-37. 10.1038/bjc.2011.185.View ArticlePubMedPubMed CentralGoogle Scholar
  12. Lehtinen M, Paavonen J, Wheeler CM, Jaisamrarn U, Garland SM, Castellsague X, Skinner SR, Apter D, Naud P, Salmeron J, Chow SN, Kitchener H, Teixeira JC, Hedrick J, Limson G, Szarewski A, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, De Carvalho NS, Germar MJ, Peters K, Mindel A, De Sutter P, Bosch FX, David MP, Descamps D, Struyf F, Dubin G, et al: Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012, 13 (1): 89-99. 10.1016/S1470-2045(11)70286-8.View ArticlePubMedGoogle Scholar
  13. Roteli-Martins CM, Naud P, De Borba P, Teixeira JC, De Carvalho NS, Zahaf T, Sanchez N, Geeraerts B, Descamps D: Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up. Hum Vaccin Immunother. 2012, 8 (3): 390-397. 10.4161/hv.18865.View ArticlePubMedGoogle Scholar
  14. Wheeler CM, Castellsague X, Garland SM, Szarewski A, Paavonen J, Naud P, Salmeron J, Chow SN, Apter D, Kitchener H, Teixeira JC, Skinner SR, Jaisamrarn U, Limson G, Romanowski B, Aoki FY, Schwarz TF, Poppe WA, Bosch FX, Harper DM, Huh W, Hardt K, Zahaf T, Descamps D, Struyf F, Dubin G, Lehtinen M, Group HPS: Cross-protective efficacy of HPV-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by non-vaccine oncogenic HPV types: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial. Lancet Oncol. 2012, 13 (1): 100-110. 10.1016/S1470-2045(11)70287-X.View ArticlePubMedGoogle Scholar
  15. Al-Badawi IA, Al-Suwaine A, Al-Aker M, Asaad L, Alaidan A, Tulbah A, Fe Bohol M, Munkarah AR: Detection and genotyping of human papilloma virus in cervical cancer specimens from Saudi patients. Int J Gynecol Cancer. 2011, 21 (5): 907-910. 10.1097/IGC.0b013e318214219f.View ArticlePubMedGoogle Scholar
  16. Alsbeih G, Ahmed R, Al-Harbi N, Venturina LA, Tulbah A, Balaraj K: Prevalence and genotypes' distribution of human papillomavirus in invasive cervical cancer in Saudi Arabia. Gynecol Oncol. 2011, 121 (3): 522-526. 10.1016/j.ygyno.2011.01.033.View ArticlePubMedGoogle Scholar
  17. Bondagji NS, Gazzaz FS, Sait K, Abdullah L: Prevalence of high-risk human papillomavirus infections in healthy Saudi women attending gynecologic clinics in the western region of Saudi Arabia. Ann Saudi Med. 2013, 33 (1): 13-17.PubMedGoogle Scholar
  18. Sait KH: Attitudes, knowledge, and practices in relation to cervical cancer and its screening among women in Saudi Arabia. Saudi Med J. 2009, 30 (9): 1208-1212.PubMedGoogle Scholar
  19. Sait KH: Knowledge, attitudes, and practices regarding cervical cancer screening among physicians in the Western Region of Saudi Arabia. Saudi Med J. 2011, 32 (11): 1155-1160.PubMedGoogle Scholar
  20. Geraets DT, van Baars R, Alonso I, Ordi J, Torne A, Melchers WJ, Meijer CJ, Quint WG: Clinical evaluation of high-risk HPV detection on self-samples using the indicating FTA-elute solid-carrier cartridge. J Clin Virol. 2013, 57 (2): 125-129. 10.1016/j.jcv.2013.02.016.View ArticlePubMedGoogle Scholar
  21. van Doorn LJ, Molijn A, Kleter B, Quint W, Colau B: Highly effective detection of human papillomavirus 16 and 18 DNA by a testing algorithm combining broad-spectrum and type-specific PCR. J Clin Microbiol. 2006, 44 (9): 3292-3298. 10.1128/JCM.00539-06.View ArticlePubMedPubMed CentralGoogle Scholar
  22. Kleter B, van Doorn LJ, Schrauwen L, Molijn A, Sastrowijoto S, ter Schegget J, Lindeman J, ter Harmsel B, Burger M, Quint W: Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol. 1999, 37 (8): 2508-2517.PubMedPubMed CentralGoogle Scholar
  23. de Sanjose S, Diaz M, Castellsague X, Clifford G, Bruni L, Munoz N, Bosch FX: Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis. 2007, 7 (7): 453-459. 10.1016/S1473-3099(07)70158-5.View ArticlePubMedGoogle Scholar
  24. Al-Muammar T, Al-Ahdal MN, Hassan A, Kessie G, Dela Cruz DM, Mohamed GE: Human papilloma virus-16/18 cervical infection among women attending a family medical clinic in Riyadh. Ann Saudi Med. 2007, 27 (1): 1-5. 10.4103/0256-4947.51540.View ArticlePubMedGoogle Scholar
  25. Central Intelligence Agency: The World factbook: Middle East: Saudi Arabia. [https://www.cia.gov/library/publications/the-world-factbook/geos/sa.html]. Last accessed: 06 Jan 2014.
  26. Cancer Incidence Report Saudi Arabia 2004. National Cancer Registry, Ministry of Health . [http://www.kfshrc.edu.sa/wps/wcm/connect/40dcba804a8d741fb731f7e404c39865/SCR2004W.pdf?MOD=AJPERES&lmod=1265914960&CACHEID=40dcba804a8d741fb731f7e404c39865]. Last accessed: 06 Jan 2014.,
  27. United Nations Statistics Division: Standard country and area codes classifications (M49). [http://unstats.un.org/unsd/methods/m49/m49regin.htm]. Last accessed: 06 Jan 2014.
  28. Turki R, Sait K, Anfinan N, Sohrab SS, Abuzenadah AM: Prevalence of human papillomavirus in women from Saudi Arabia. Asian Pac J Cancer Prev. 2013, 14 (5): 3177-3181. 10.7314/APJCP.2013.14.5.3177.View ArticlePubMedGoogle Scholar
  29. Alsbeih G, Al-Harbi N, El-Sebaie M, Al-Badawi I: HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia. Infect Agent Cancer. 2013, 8 (1): 15-10.1186/1750-9378-8-15.View ArticlePubMedPubMed CentralGoogle Scholar
  30. Mackay J: Global sex: sexuality and sexual practices around the world. Sex Relation Ther. 2001, 16 (1): 71-82. 10.1080/14681990123347.View ArticleGoogle Scholar
  31. Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjose S: Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010, 202 (12): 1789-1799. 10.1086/657321.View ArticlePubMedGoogle Scholar
  32. Davis MA, Gray RH, Grabowski MK, Serwadda D, Kigozi G, Gravitt PE, Nalugoda F, Watya S, Wawer MJ, Quinn TC, Tobian AA: Male circumcision decreases high-risk human papillomavirus viral load in female partners: A randomized trial in Rakai. Uganda Int J Cancer. 2013, 133 (5): 1247-1252. 10.1002/ijc.28100.View ArticlePubMedGoogle Scholar
  33. Morris BJ, Mindel A, Tobian AA, Hankins CA, Gray RH, Bailey RC, Bosch X, Wodak AD: Should male circumcision be advocated for genital cancer prevention?. Asian Pac J Cancer Prev. 2012, 13 (9): 4839-4842. 10.7314/APJCP.2012.13.9.4839. Demographics of Saudi Arabia [http://www.princeton.edu/~achaney/tmve/wiki100k/docs/Demographics_of_Saudi_Arabia.html]. Last accessed: 06 Jan 2014,View ArticlePubMedPubMed CentralGoogle Scholar
  34. Towards a Stratergy for Cancer Control in the Eastern Mediterranean Region. [http://applications.emro.who.int/dsaf/dsa1002.pdf]. Last accessed: 06 Jan 2014.
  35. Education at a Glance 2012. [http://www.oecd.org/edu/highlights.pdf]. Last accessed: 06 Jan 2014.
  36. Gazzaz FB: Molecular testing of human papillomavirus in cervical specimens. Saudi Med J. 2007, 28 (12): 1810-1818.PubMedGoogle Scholar

Copyright

© AlObaid et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Advertisement