INTRODUCTION

Globally, cervical cancer is the fourth most common cancer in women with an estimated 570,000 new cases in 2018 representing 6.6% of all female cancers. Approximately 90% of deaths from cervical cancer occurred in low and middle-income countries.^[1] Infection with Human Papillomavirus (HPV) is a major cause of cervical cancer. Evidence shows that HPV also strongly linked to developing cancer of oropharynx, anus, vulva, penis, and vagina. HPV strain 16 and 18 can cause 70% of precancerous lesions and cancer of the cervix.

According to the Catalan Institute of Oncology (ICO)/International Agency for Research on Cancer (IARC) estimates of 2018, in India, cervical cancer ranks 2^nd most common leading cause of female cancer and female cancer deaths. In India, about 96,922new cases and 60,078 deaths were reported on cervical cancer in 2018. The prevalence of HPV 16/18 strains induced cervical cancer was 83.2% (81.5-84.8) in India.^[2] HPV 6 and 11 types are majorly associated to develop genital warts.^[3]

HPV vaccination is a primary prevention measure to control cervical cancer. There are two types of HPV vaccines (Bivalent and Quadrivalent) licensed in India in 2006. The bivalent vaccine gives protection against HPV 16 and 18 strains, whereas the quadrivalent vaccine covers HPV 6, 11, 16, and 18 strains.^[4] These vaccines are available only on demand at some private hospitals in India. Globally, around 80 countries introduced HPV vaccination into their national routine vaccination schedule. ^[5] Indian Academy of Pediatrics added the HPV vaccine into the list of recommended vaccination. Evidence shows that vaccination will reduce the burden of cervical cancer in India, but vaccines are still not available in the national routine immunization program. ^[6] In 2017, the World Health Organization (WHO) Executive Board emphasized about HPV vaccination of 9-14 years old girls is one of the 5 recommended interventions against non-communicable diseases. ^[7]

The global evidence strongly suggesting that, HPV vaccination will reduce the incidence, morbidity, mortality, and costs associated with cervical cancer. The acceptability of the HPV vaccination in India is still controversial due to high cost, stigma, and lack of knowledge, safety, and efficacy concerns. The safety issues related to HPV vaccination were highlighted in the report of 2010 that, four tribal women were dying due to adverse events in the HPV vaccination project led by a global non-governmental organization in Andhra Pradesh. ^[8] Although the reports of the projects shown that deaths are not associated with the HPV vaccine, due to negative media coverage still most of the people in India believe that vaccines will induce serious adverse effects. ^[9]

In middle-income countries like India, cost plays a vital role in the acceptance of the vaccine, which is not available in the routine immunization program. The cost of HPV vaccination is 12,000 INR (approximately USD) for three doses. The average annual per capita income in India of 1,36,405 (2017-2018). ^[10]About 11.4% of the annual income has to be spent on HPV vaccination. The addition of HPV vaccination in routine immunization programs will reduce the burden of cost for vaccination. Most of the cervical cancer cases in India were reported in the advanced stage due to a lack of awareness and accessibility of the screening program. ^[11] The HPV vaccine will reduce the detection rate of cervical cancer, but it is not an alternative to cervical cancer screening.

Health care providers Knowledge, Attitude, and recommendations play a vital role in the acceptance of HPV vaccination among adolescent girls. Parents purely depend on the recommendations given by the health care provider’s weather to vaccinate their children or not. After termination of the HPV vaccination project led by a global non-governmental organization in Andhra Pradesh, this is the primary study conducted in this state to know the KAP of health care workers in the recommendation of HPV vaccination. The data generated in this study will have a great scope in the incorporation of HPV vaccination in the routine immunization of the program. This study aims to evaluate the Knowledge, Attitude, and Practice (KAP) of physicians in the recommendation of the HPV vaccination.

MATERIALS AND METHODS

A cross-sectional study was conducted between May 2019 and October 2019 in Anantapuramu District, Andhra Pradesh, India. Anantapuramu is the largest district in the state of Andhra Pradesh in Southern India. A total of Government hospitals, private hospitals, Primary Health Centers (PHCs), and Non-Profit Organization (NGO) Hospitals are involved in providing immunization facilities to the residents of Anantapur district. Physicians practicing in the area of Obstetrics& Gynecology, Pediatrics, Oncology, Family Medicine, Infectious Diseases, and primary care centers were included in the study. These physicians are more likely to recommend HPV vaccination in their practice. There were no financial or material incentives for participation. The study was approved by the Institutional Review Board (IRB) with an approval number of RIPER/IRB/PP/2019/001. Written informed consent was obtained from the physicians after explanation of the study objectives and expected outcomes.

Sample size and sampling technique:

The number of physicians to be included in the study was calculated by using a single population proportion formula. By considering 80% of the HPV vaccine acceptance rate (p) from the previous studies, 95% confidence interval, 80% power, 5% margin of error (d), and the sample size was calculated as246. Because there may be dropouts or insufficient data or incomplete data sample size was increased by 20% to about 296. A convenient sampling technique was used to select the physicians from different hospital settings (Government, Private, PHC, and Trust) providing immunization facilities in Anantapur district.

Survey instrument:

Validation of KAP Questionnaire:

The KAP questionnaire was subjected to face validation by a panel of experts comprising of a gynecologist (1), pediatrician (1), oncologist (1), epidemiologist (1), and anthropologist (1). Knowledge domain contains 30 questions (HPV infection-16; HPV vaccine-14), attitude domain 5 questions, and practice domain 6 questions. Expert opinion towards each item was placed on a four-point Likert scale ranging strongly agree 4, agree 3, disagree 2, and strongly disagree 1. The Scale level Content Validity Index (S-CVI) for knowledge (HPV infection and vaccination), attitude, and practice domains were estimated as 0.9, 0.84, and 0.9 (≥0.8 acceptable).

KAP questionnaire

The questionnaire encompasses four parts to collect data regarding the socio-demographic profile of study physicians and KAP towards HPV vaccine recommendation. The socio-demographic characteristics include age, gender, marital status, qualification, practice location, hospital type, specialty, experience, workload, and age of the patients primarily consulted.

Knowledge about HPV infection and HPV vaccination:

Knowledge regarding HPV infection was assessed by using a 14 - point scale. There were 16 knowledge related questions (HPV infection) that carry 14 correct answers. Each correct answer was given a point of ‘1’ and wrong answer a point of ‘0’. The maximum expected points were 14 and a minimum of zero. Points to aware about HPV infection is sexually transmitted disease (1 point), HPV infection causes cervical cancer (1 point), HPV 16 and 18 strains causes’ cervical cancer (1 point), HPV 6 and 11 strain causes genital warts (1 point), both men and women infected with HPV (1 point), HPV causes vulvar, vaginal and anal cancer in women (1 point), HPV causes anal cancer in men (1 point), HPV causes head and neck cancer (1 point), HPV infection is high in women age 20s and 30s (1 point), HPV infection is asymptomatic (1 point), HPV detection is not possible by PAP smear, PCR and biopsy (1 point) blood test used in HPV detection (1 point), treatment of cervical dysplasia not eliminates HPV (1 point), and condom use does not prevent HPV transmission (1 point).

Knowledge regarding HPV vaccination was assessed by using a 10 point scale. There were 14 HPV vaccine-related knowledge questions that carry 11 correct answers. Each correct answer was given a point of ‘1’ and wrong answer a point of ‘0’. The maximum expected points were 11 and a minimum of zero. Points to physician aware about several vaccines available in the Indian market (1 point), name of the vaccines (1 point), Use of Cervarix in only females & Gardasil in both males and females (1 point), vaccine recommended age group (1 point), route of administration (1 point), the recommendation of HPV vaccine irrespective of HPV infection (1 point), HPV vaccine protects against cervical cancer and genital warts (1 point), vaccination is not a substitute for screening (1 point), HPV vaccine is contraindicated in pregnancy (1 point), and HPV vaccine offers >90% efficacy (1 point). Knowledge regarding HPV infection and vaccination was divided into three categories based on original blooms cut off criteria. According to the criteria, if the physician gives 80-100% correct responses meant good knowledge, 60-79%  correct responses meant a moderate knowledge, and  <60% correct responses meant a poor knowledge.

Attitude towards HPV vaccine recommendation:

The physician’s attitude towards the barriers of HPV vaccine recommendation was assessed by five dichotomous answerings (Yes/No) statements. The barriers identified and evaluated are high cost, doubt of efficacy, safety concerns, HPV has sexually transmitted infection, and unavailability of the vaccine in the universal immunization program.

Practices of HPV vaccine recommendation:

A total of six questions were used to assess the practices of physicians to HPV vaccine recommendation. The first question is; “have you recommended HPV vaccine to your client”. If the physician says ‘yes’, he/she will be allowed to answer the remaining five questions about the rational practice. Rational practices included are; Advice of PAP smear even women get vaccinated, HPV vaccine advice after detection of precancerous lesions, vaccine not advised in pregnant women, following standard dosing schedule, and recommendation in the appropriate age group. The rational practice was confirmed if the physician adheres to all the above practices during HPV vaccination recommendation.

Statistical analysis:

Epi-Info 7 for Dos version 3.5.1 software (Centers for Disease Control and Prevention, Clifton Road Atlanta, USA) was used to analyze the data. Descriptive statistics (mean, standard deviation, frequency, and proportion) were used to represent the socio-demographic characteristics and KAP of the study physicians. Inferential statistics like, the chi-square test was used to associate socio-demographics with good knowledge and regular practice towards the HPV vaccine. P <0.05 was considered a statistically significant result.

RESULTS

A total of 296 physicians were answered the KAP questionnaire, in these majority (118; 31.8%) are between 20 and 30 years, with a mean age of 35.84±10.12. The majority of the respondents were males (160; 54.0%), practices in urban areas (138; 46.6%), and working in a private hospital (152; 51.3). Doctors from general medicine (128; 43.2%), OBG (85; 28.7%), and pediatric (72; 24.3%) departments were high in our study. More than half of the respondents were having less than 10 years’ experience (196; 66.2%).  The majority of the physicians are treating all age groups of patients (186; 62.8%) and working less than or equal to eight hours (222; 75.0%) as shown in Table 1.

Among 296 physicians, 3/4^th of them are aware of the HPV infection is transmitted through sex (226; 89.8%), HPV 16 and 18 strains cause cervical cancer (250; 84.4%), HPV infects both men and women (246; 83.1%), HPV causes vulvar, vaginal, and anal cancers in women (238; 80.4%), types of vaccines available in the Indian market (256; 86.5%), and names of the vaccines (260; 87.8%). Less than half the respondents are aware of detection methods for HPV infection (44; 14.8%), treatment of cervical dysplasia doesn’t eliminate HPV (134; 45.3%), and condom use does not help in the prevention of HPV infection (100; 33.8%). More than half of the respondents have answered all questions related to HPV vaccination as depicted in Table 2. 

Among all respondents, more than half of them were believed that the HPV vaccine is costly (232; 78.4%), not effective (186; 62.8%), and not safe (176; 59.4%) are the major barriers for the poor recommendation. Because HPV is a sexually transmitted infection (197; 66.5%), and unavailability of vaccine (223; 75.3%) in the universal immunization program are also obstacles for the vaccine recommendation. Only, (99; 33.4%) of physicians are recommending the HPV vaccine in their routine practice. Among 99 practicing physicians, less than 30% adheres to rational practicing procedures as shown in Table 3.

Among all physicians, 35 (13.2%) have good knowledge, 142 (47.9%) moderate knowledge, and 115 (38.8%) poor knowledge about HPV infection. Knowledge towards HPV vaccination revealed, 131 (43.9%) have good knowledge, 92 (31.1%) moderate knowledge, and 74 (25.0%). Among 296 physicians, only 99 are recommending the HPV vaccine for their clients. In these, the majority (77; 77.7%) are having irrational practice as represented in Table 4.

Socio-demographic characteristics like age, location of practice, type of working hospital, specialty, healthcare experience, and age of patients primarily treated are significantly associated with good knowledge and regular practice towards HPV vaccine recommendation as represented in Table 5.

Among all identified barriers, the “HPV vaccine is not safe” is one of the major barriers strongly associated with low recommendation with a P-value 0.006. An association of all identified barriers towards vaccine recommendation was represented in Table 6.

DISCUSSION

Optimal knowledge about the HPV vaccine among physicians is an essential requirement to educate and recommend the vaccine. Evidence shows that physician recommendation is an essential and reliable predictor for vaccine acceptance. ^[12] Our study findings explore the insights of the physician’s knowledge, and practices of HPV vaccine recommendation in and around Anantapur district, India, as well as investigating the physician attitude towards major barriers for HPV vaccine recommendation.

Our study findings reveal that, only 52% of the physicians are aware of HPV causes some neck and head cancers. Our findings are even very less compared to the findings (57.1%) of the study conducted by AbiJaoude J et al in Lebanon. ^[13] An Indian cohort study findings revealed that, 32% of the head and neck squamous cell cancer (HNSCC) patients were positive for HPV. ^[14] This evidence strongly highlights the need for awareness regarding HPV links to HNSCC.

The study physicians falsely believe that, condom use prevents HPV infection, dysplasia treatment eliminates HPV, and HPV detection is not possible by a blood test. There is a need to address and fulfill the knowledge gap exists among our study physicians regarding, the link between HPV infection and HNSCC, condom use cannot prevent HPV infection, treatment of cervical dysplasia not eliminate HPV, and a simple blood test is enough to detect HPV infection.

Findings of knowledge about HPV vaccine reveal that, very few physicians aware (160; 54.0%) about the use of Cervarix is only for females and Gardasil can be used in both males and females. According to WHO guidelines, the primarily targeted age group for vaccination was 9-14 years and the secondary target was more than 15 years. ^[15] Physicians knowledge about, HPV vaccine recommendation between the age of 9 and 14 years (172; 58.1%), administered through IM route (160; 54.0%), and not or less effective in HPV infected people (136; 45.9%).  In broad, the overall knowledge towards HPV infection and vaccination is moderate (142; 47.9%, 92; 31.1%) and poor (115; 38.8), 74; 25.0%) among physicians practicing in Anantapur District.  A similar report type is also observed in the studies conducted in other regions of India. ^[16-18]

Physicians strongly believing that, high cost (232; 78.4%) is one of the major barriers for HPV vaccine acceptance among the public. Nearly similar results are also observed in a study conducted by Belani HK et al in Bangalore, India. ^[19] A previous hospital-based study on KAP towards cervical cancer among women in Anantapur district, revealed the majority of the participants are low-economic background. ^[20] These findings support cost is one of the major barriers existing in HPV vaccine acceptance.

Majority of physicians are considering, unavailability of vaccine in UIP (223; 75.3%), sexual transmitted nature of HPV (197; 66.5%), HPV vaccine is not effective (186; 62.8%) and safe (176; 59.4%) are the major barriers for HPV vaccine recommendation. Physicians are more concerned regarding the negative parental reaction to discuss sexually transmitted infections and vaccination for their children. Doubt about the safety and efficacy of the vaccine is nearly similar to the findings of the study conducted by Garbutt JM et al. ^[21]

Our study shows that, only 33.4% of the physicians are recommending the HPV vaccine for their clients. Physician practices are very low compared to the findings (47%) of the study conducted in New Delhi by Chawla et al. ^[6] This wide difference may be due to, physicians practicing in New Delhi may have excessive exposure towards updates of HPV vaccine than physicians in Anantapur district.

The study findings reveal that, physicians age, type of working hospital, specialty, healthcare experience, and age of patients primarily consulted were significantly associated with knowledge about HPV infection and (or) HPV vaccination.  Physicians practicing in an urban location, and community medicine specialty were significantly associated with the high practice of vaccine recommendation. These findings help in the planning of targeted, structured educational, or CME programs to physicians in improving knowledge and practice towards HPV vaccine recommendation.

Physician practice towards HPV vaccine recommendation was significantly (P 0.006) associated with a barrier (use of HPV vaccine is not safe). This false belief among physicians needs to be addressed to improve the practice of HPV vaccine recommendation.

Strengths and limitations:

The study was limited to hospitals located in Anantapur district, Andhra Pradesh, India. There is a necessity to expand this research in various regions of India, whether the findings are reproducible or not. Physicians are enrolled in the study by using a convenient sampling technique, so, the time and day of visit to the hospital may influence the response towards the KAP questionnaire. This is the prime KAP study conducted among physicians in Andhra Pradesh state. These results help in addressing issues related to poor HPV vaccine recommendations.

CONCLUSION

We conclude, the majority of the physicians had moderate or poor knowledge about HPV infection and vaccine. Only, 33.4% of the physicians are recommending the HPV vaccine to their clients. Poor knowledge, false attitude, or belief about existing barriers (high cost, non-efficacious, STD, unsafe, non-availability in UIP) of the HPV vaccine are the major reasons for the low practice among physicians. So, there is a need to improve physician knowledge, and eliminate false beliefs about barriers towards HPV vaccine recommendation before the implementation of vaccines in the routine immunization programs.

Conflict of interest: Nil

ACKNOWLEDGMENT

The authors would like to thank all physicians who are involved in this research study. All the authors are wholeheartedly thankful to the people who are directly or indirectly responsible for the completion of the work.

REFERENCES

1. Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. International journal of cancer. 2019 Apr 15;144(8):1941-53.
2. Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, Muñoz J, Bosch F, de Sanjosé S. ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). human papillomavirus and related diseases in the world. Summary report 27 July 2017.
3. Lacey CJ, Lowndes CM, Shah KV. Burden and management of non-cancerous HPV-related conditions: HPV-6/11 disease. Vaccine. 2006 Aug 21;24:S35-41.
4. Kaur P, Mehrotra R, Sankaranarayanan Rengaswamy TK, Hariprasad R, Mehendale SM, Rajaraman P, Rath GK, Bhatla N, Krishnan S, Nayyar A, Swaminathan S. Human papillomavirus vaccine for cancer cervix prevention: Rationale & recommendations for implementation in India. The Indian journal of medical research. 2017 Aug;146(2):153.
5. Jaoude JA, Khair D, Dagher H, Saad H, Cherfan P, Kaafarani MA, Jamaluddine Z, Ghattas H. Factors associated with Human Papilloma Virus (HPV) vaccine recommendation by physicians in Lebanon, a cross-sectional study. Vaccine. 2018 Nov 26;36(49):7562-7.
6. Chawla PC, Chawla A, Chaudhary S. Knowledge, attitude & practice on human papillomavirus vaccination: A cross-sectional study among healthcare providers. The Indian journal of medical research. 2016 Nov;144(5):741..
7. WHO. 140th Meeting of the WHO Executive Board discusses revised menu of policy options for addressing noncommunicable diseases (NCDs) (Rep.); 201
8. Larson HJ, Brocard P, Garnett G. The India HPV-vaccine suspension. Lancet. 2010;376(9741):572-3.
9. Sinha K. Four deaths not due to flawed cervical cancer vaccine trial. The Times of India. 2010.
10. An overview of India’s Economic Performance 2017-2018
11. Nigam A, Saxena P, Acharya AS, Mishra A, Batra S. HPV vaccination in India: critical appraisal. ISRN obstetrics and gynecology. 2014 Mar 11;2014.
12. Vadaparampil ST, Kahn JA, Salmon D, Lee JH, Quinn GP, Roetzheim R, Bruder K, Malo TL, Proveaux T, Zhao X, Halsey N. Missed clinical opportunities: provider recommendations for HPV vaccination for 11–12 year old girls are limited. Vaccine. 2011 Nov 3;29(47):8634-41.
13. Jaoude JA, Khair D, Dagher H, Saad H, Cherfan P, Kaafarani MA, Jamaluddine Z, Ghattas H. Factors associated with Human Papilloma Virus (HPV) vaccine recommendation by physicians in Lebanon, a cross-sectional study. Vaccine. 2018 Nov 26;36(49):7562-7.
14. Singh S, Nautiyal V, Chauhan N, Gupta M, Ahmad M. The association of human papillomavirus infection in indian cohort of head-and-neck squamous cell cancer patients and its impact on treatment outcome. Clinical Cancer Investigation Journal. 2017 Nov 1;6(6):247.
15. WHO. Summary of the WHO position paper on vaccines against Human Papillomavirus (HPV) May. World Health Organization; 2017.
16. Canon C, Effoe V, Shetty V, Shetty AK. Knowledge and attitudes towards human papillomavirus (HPV) among academic and community physicians in Mangalore, India. Journal of Cancer Education. 2017 Jun 1;32(2):382-91.
17. Krupp K, Marlow LA, Kielmann K, Doddaiah N, Mysore S, Reingold AL, Madhivanan P. Factors associated with intention-to-recommend human papillomavirus vaccination among physicians in Mysore, India. Journal of adolescent health. 2010 Apr 1;46(4):379-84.
18. Tsu VD, Cernuschi T, LaMontagne DS. Lessons learned from HPV vaccine delivery in low-resource settings and opportunities for HIV prevention, treatment, and care among adolescents. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2014 Jul 1;66:S209-16.
19. Belani HK, Sekar P, Guhaniyogi R, Abraham A, Bohjanen PR, Bohjanen K. Human papillomavirus vaccine acceptance among young men in Bangalore, India. International journal of dermatology. 2014 Nov;53(11):e486-91.
20. Narayana G, Suchitra MJ, Sunanda G, Ramaiah JD, Kumar BP, Veerabhadrappa KV. Knowledge, attitude, and practice toward cervical cancer among women attending Obstetrics and Gynecology Department: A cross-sectional, hospital-based survey in South India. Indian journal of cancer. 2017 Apr 1;54(2):481.
21. Garbutt JM, Dodd S, Walling E, Lee AA, Kulka K, Lobb R. Barriers and facilitators to HPV vaccination in primary care practices: a mixed methods study using the Consolidated Framework for Implementation Research. BMC family practice. 2018 Dec;19(1):53.