Factors Associated with Presence of Human Papillomavirus Infection among Women: Findings from New Cervical Cancer Screening in Kelantan, Malaysia

@#Introduction: Human papillomavirus (HPV) infection is known to cause cervical cancer worldwide. Recently, Malaysia introduced HPV DNA detection testing for cervical cancer screening program. However, knowledge regarding factors for HPV infection among women still limited. Thus, this study aimed to determine the prevalence and factors associated with HPV infection among women in Kelantan, a north-eastern state of Malaysia. Methods: This study used secondary data extracted from HPV DNA test registry book and HPV DNA laboratory request forms. Data on all Malaysian women aged 30 to 49 years old in 2019 reported in registry book were included. Simple random sampling was applied. All information from book and forms were collected using proforma and analysed using SPSS. The outcomes were categorised into HPV infection and non-HPV infection. The parameters related to factors associated with HPV infection were determined using multivariable logistic analysis. Results: The prevalence of HPV infection among women attending the new cervical screening was 8.4% (95% CI 6.4%, 10.3%). Those aged between 30 and 39 years old (AdjOR 2.09; 95% CI 1.16, 3.78, p=0.014), had 5 or more parities (AdjOR 2.82; 95% CI 1.58, 5.06, p<0.001) and hormonal contraception users (AdjOR 7.48; 95% CI 4.07, 13.76, p<0.001) were significantly associated with HPV infection. Conclusion: Overall, the prevalence of HPV infection from this study is comparable to the local and international studies. Age, number of parities and hormonal contraception users influence the HPV infection. This finding could help in designing more targeted screening for cervical cancer.

Avaliação de métodos diagnósticos, morfológicos e biomoleculares em mulheres encaminhadas com citologia alterada / The diagnostic efficacy of morphologic and molecular methods in women with abnormal citology

Introdução: o câncer do colo uterino é a neoplasia mais frequente em mulheres de países em desenvolvimento. Doença causada pela infecção persistente com diferentes tipos de papilomavírus humano (HPV) classificados em baixo e alto risco, de acordo com o potencial oncogênico. Objetivo: em mulheres com diagnóstico citopatológico anormal por ocasião de exame de rastreamento do câncer cervical, encaminhadas por diferentes postos de atendimento do Sistema Único de Saúde para serviço universitário de referência e com diagnóstico definitivo de lesão intraepitelial de alto grau ou câncer cervical, avaliara eficácia diagnóstica de métodos morfológicos e biomoleculares utilizados de maneira isolada ou em associação; e a prevalência, estratificada em duasfaixas etárias, abaixo de 30 e igual ou superior a 30 anos, do HPV tipos 16, 18 e 45. Métodos: estudaram-se 167 mulheres encaminhadas ao Ambulatório de Patologia Cervical e Colposcopia do Hospital Universitário da Universidade Federal de Juiz de Fora, no período de novembro de 2002 e dezembro de 2003,com colo uterino íntegro, não grávidas e sem história de câncer no trato genital inferior. Coletaram-se, de todas as mulheres, amostras para estudo citológico,convencional e em meio líquido, e para os testes de DNA-HPV. Considerou-se como diagnóstico histopatológico final a avaliação mais grave dentre ospossíveis espécimes, biópsia, conização ou peça cirúrgica, que a paciente pudesse ter. Resultados: não há qualquer diferença no tocante à sensibilidade,ao valor preditivo positivo e negativo e à acurácia dentre os métodos diagnósticos estudados, porém a associação da citologia com o teste DNA-HPV tem menor especificidade que o exame citológico isolado, quer convencional ou em meio líquido. A prevalência do HPV 16, 18 e 45 cai de 88,9% para 50,0%nas mulheres com 30 anos ou mais (p = 0,02). Conclusão: nas mulheres encaminhadas ao ambulatório de PTGIC do HU-UFJF com colpocitologia alteradanão se justifica a realização de qualquer exame confirmatório, devendo realizar-se imediatamente a colposcopia para se ter o desfecho diagnóstico.

Introduction: cervical cancer is the most frequent neoplasia among the women of countries in development. Great part of these cases is caused by persistent infection with different types of human papilomavirus (HPV) classified as low and high risk, according to the risk of cervical cancer development. Objectives:based on women with abnormal cytology when screening for cervical cancer who were led from different units of the Public Health System to the reference university service and with a definite diagnosis of high cervical intraepithelial neoplasia or cancer, was to evaluate the diagnostic efficacy of morphologicand molecular methods used alone or together and the prevalence of HPV types 16, 18, 45, stratified into two age brackets. Methods: 167 women went to the Cervical Pathology and colposcopy clinic of the University Hospital of the Universidade Federal de Juiz de Fora, during the period from November 2002 to December 2003, with intact uterine cervix, not pregnant and without previous chemical and/or radiotherapy treatment for the inferior genital tract.Samples for cytology study were collected from all women, with conventional and liquid-based preparations, for CH2 for high risk virus, for DNA PAP andfor Probe Pack test. The worst histologic diagnosis among the possible histologic studies through biopsy, conization or cirurgic pieces was considered as "gold standard". Results: there is no difference regarding sensibility, positive predict value and negative predict value for all methods studied, However, the DNA PAP method has less specificities than the citology exam, either with conventional or based-liquid preparation. The prevalence of HPV 16, 18, 45 decreases from 88,9% to 50% in women of 30 years old or more, being this decrease statistically significant. Conclusion: in those women led to the PTGIC of the HUUFJF with abnormal cytology it is not necessary to repeat any tests, just colposcopy in order to reach the final diagnosis.

Detection of human papillomavirus type 16 and 18 by PCR in patients with cervical neoplasia / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to evaluate the detection rate of human papillomavirus (HPV) DNA Test (type 16 and 18) and to investigate the clinical significance of HPV DNA test in patients with cervical neoplasia. METHODS: Of the 708 patients aged 21~83 years who had undergone both conventional Papanicolaou cervical cytologic test and HPV DNA test by polymerase chain reaction, 383 cases underwent histologic diagnoses. RESULTS: Of the 708 cytologic diagnoses, there were 11 positive HPV DNA test diagnoses in squamous cell carcinoma (SCC), 41 in high-grade squamous intraepithelial lesion (HSIL), 20 in low-grade squamous intraepithelial lesion (LSIL), 41 in atypical squamous cells (ASC), and 86 in negative cytology. Of the 383 histologic diagnoses, there were 24 positive HPV DNA test diagnoses in SCC, 42 in cervical intraepithelial neoplasia (CIN) 3, 12 in CIN 2, 12 in CIN 1, 7 in atypical change, and 45 in negative histology. Of the 239 patients with negative HPV DNA test, 28.5% cases showed histologic diagnoses of CIN 1 or worse lesion. Of the 46 patients with negative cytology and positive HPV DNA test, 50.0% cases showed histologic dianoses of CIN 1 or worse lesion. Pap cytology revealed sensitivity of 72.5%, specificity of 66.4%, and false negative rate of 27.5%, whereas HPV DNA test showed 57.5%, 76.7%, and 42.5%, respectively. CONCLUSION: This study confirmed that the primary standard Pap cytology and HPV DNA test were adjunctive. Also this study showed that physicians always should not overrate Pap cytology or HPV DNA test in managing the patient with cervical neoplasia. Combined test was a very effective diagnostic method for detecting cervical neoplasia.

The comparative evaluation of clinical screening in combined tests cytology (ThinPrep(R)), HPV DNA test (Hybrid capture(R) II),cervicography for uterine cervical cancer / 부인종양

OBJECTIVE: Since the accuracy of Pap smear for cervical neoplasm has been questioned, a number of adjunctive tests have been developed. The purpose of this study was to evaluate which protocol is the most effective screening test among cervical cytology (ThinPrep(R)), HPV DNA test (Hybrid capture(R) II) and cervicography. METHODS: We chose 252 patients who were underwent the biopsy among 829 patients who visited our hospital for cervical cancer screening test. These 252 patients were engaged in this study simultaneously. They underwent triple combined test [cervical cytology (ThinPrep(R)), HPV DNA test (Hybrid capture(R) II), cervicography] and colposcopic-directed biopsy or biopsy on operation for diagnostic evaluation. RESULTS: The triple combined test showed a sensitivity of 96.0%, while double combined test [cervical cytology (ThinPrep(R))+cervicography] showed a sensitivity of 89.0%, the other double combined test [cervical cytology (ThinPrep(R))+HPV DNA test (Hybrid capture(R) II)] showed a sensitivity of 86.7%. Cervicography showed a specificity of 75.4% (highest among the single test), positive predictability of 89.8% (also highest). CONCLUSION: The sensitivity of cervical cytology was markedly improved by combination with HPV DNA test and cervicography. So the triple combined tests which improved the high false negative rate of cervical cytology may be a new effective method as a cervical cancer screening test, if the effectiveness could be confirmed by mass screening study.

Clinical Efficacy of Human Papillomavirus DNA test after Loop Electrosurgical Excision Procedure in Cervical Intraepithelial Neoplasia / 대한산부인과학회지

OBJECTIVE: The aim of this study was to analyze a relation between the recurrence of cervical intraepithelial neoplasia (CIN) and the detection of high-risk human papillomavirus (HPV) DNA after loop electrosurgical excision procedure (LEEP), and to evaluate the clinical efficacy of HPV DNA test by Hybrid Capture Assay as a predictor of the recurrence of CIN after LEEP. METHODS: From January 2000 through March 2003, the charts of 238 women diagnosed as CIN and treated with LEEP were reviewed retrospectively. HPV DNA test (Hybrid Capture System I) for high-risk HPV was performed in all patients before LEEP. They were followed up with Papanicolaou smears and HPV DNA tests at the interval of 3 months during the first 6 months and then at the interval of 6 months. The Chi-square test was used for the statistical analysis. RESULTS: The rate of detection of high-risk HPV declined chronologically after LEEP. A higher recurrence rate was noted in the HPV DNA positive group after LEEP, comparing with the negative group, at 3 months (54.5% in positive vs. 6.5% in negative; p<0.05), at 6 months (61.1% in positive vs. 5.4% in negative; p<0.05), at 12 months (50.0% in positive vs. 14.0% in negative; p<0.05), and at 18 months (50.0% in positive vs. 15.2% in negative; p<0.05). The negative predictive value was high at 3 months (93.5%), at 6 months (94.6%), at 12 months (86.0%), and at 18 months (84.6%). There were significant associations between the recurrence of CIN and positive resection margin except for glandular involvements. CONCLUSION: The detection of high-risk HPV is a risk factor for the presence of CIN after LEEP. HPV DNA test by Hybrid Capture Assay after LEEP may be useful marker for the negative prediction of recurrence of CIN after LEEP.

Resection margin status and HPV DNA test as predictor of residual lesion after cervical conization in the management of CIN 3 / 부인종양

OBJECTIVE: To identify resection margin status and HPV DNA test as predictive factors for residual lesion in the management of CIN3 with cervical conization. METHODS: A retrospective study was conducted on 96 patients with CIN3 who had been performed cervical conization (LEEP or CKC) between January 1999 and December 2003 at Soonchunhyang university Chunan hospital. Secondary conization or hysterectomy were performed in case of positive margin on cone specimen or negative margin with other hysterectomy indication. Resection margin status and pre conization HPV DNA test were compared with residual lesion on subsequent cone or hysterectomy specimen. RESULTS: Among 96 cases, 24 cases (15.6%) showed positive resection margin on cone specimen. Of 24 cases with positive resection margin, 2 cases were followed up without treatment, 2 cases were treated with secondary conization and 20 cases were treated with hysterectomy. Of 72 cases with negative resection margin, hysterectomy was performed due to other indication in 16 cases. Persistence of residual lesion in the secondary conization and hysterectomy specimens was significantly correlated with high risk HPV infection and positive resection margin status (p<0.05). CONCLUSION: Conization is good treatment modality of the management of CIN3. HPV DNA test and resection margin status are good predictor of residual lesion after cervical conization for the management of CIN 3. Therefore, when HPV positive and resection margin positive, secondary treatment is mandatory.

Identification of High Risk Group of HPV associated with Cervical Cancer in Korean Women / 대한산부인과학회잡지

OBJECTIVE: To identify genital HPV types and high risk group of HPV associated with cervical cancer in Korean women. METHODS: Both Pap test and HPV-DNA test using PCR assay were performed as screening test for cervical cancer in this clinic. When patients were positive in HPV-DNA test, HPV genotyping using sequencing method and cervical biopsy were performed. RESULTS: Frequent age group of HPV infection was 40 yrs (34.3%) and prevalence of HPV infection was 9.8%. Twenty-three types of HPV were detected. HPV 16 and 58 were detected in invasive cancer. HPV 16, 31, 33, 45, and 58 were detected in HSIL. HPV 6, 11, 18, 53, 59, and 66 were detected in LSIL. HPV 16 was most commonly detected in HSIL and invasive cancer. CONCLUSION: HPV 16, 31, 33, 45, and 58 are included in high risk group of HPV in Korean women. It may be very effective in early detection of cervical cancer to classify HPV types included in high risk group of cervical cancer in Korean women and to perform cervical biopsy in the patients who have high risk types of HPV infection.

Identification of High Risk Group of HPV associated with Cervical Cancer in Korean Women / 대한산부인과학회잡지

OBJECTIVE: To identify genital HPV types and high risk group of HPV associated with cervical cancer in Korean women. METHODS: Both Pap test and HPV-DNA test using PCR assay were performed as screening test for cervical cancer in this clinic. When patients were positive in HPV-DNA test, HPV genotyping using sequencing method and cervical biopsy were performed. RESULTS: Frequent age group of HPV infection was 40 yrs (34.3%) and prevalence of HPV infection was 9.8%. Twenty-three types of HPV were detected. HPV 16 and 58 were detected in invasive cancer. HPV 16, 31, 33, 45, and 58 were detected in HSIL. HPV 6, 11, 18, 53, 59, and 66 were detected in LSIL. HPV 16 was most commonly detected in HSIL and invasive cancer. CONCLUSION: HPV 16, 31, 33, 45, and 58 are included in high risk group of HPV in Korean women. It may be very effective in early detection of cervical cancer to classify HPV types included in high risk group of cervical cancer in Korean women and to perform cervical biopsy in the patients who have high risk types of HPV infection.

Cervicography and HPV DNA Testing as Triage Criteria for Women with Abnormal Pap Smear by Primary Care Clinicians / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was to determine the predictive values of cervicography and HPV DNA test for histologic CIN diagnoses among women with abnormal cervical cytology so as to use as an intermediate triage criteria by primary care clinicians. METHODS: All 129 patients with abnormal cervical cancer screening tests underwent simultaneous or consecutive cervicography, HPV DNA test, colposcopically directed punch biopsy and/or LEEP. The results of single or combination screening tests were compared with final histopathologic findings. 71 among 129 patients were referred from other clinics, and remainders from mine between July 2000 and June 2001. RESULTS: Sensitivity/Specificity/PPV/NPV/Efficiency and FPR/FNR of single or combination tests were calculated. Following results were obtained. 1) Sensitivity : Triple combined test was 100%, double combined test by cytologic test plus either cervicography or HPV DNA test (97.8%), cytologic test (94.6%), HPV DNA test (88.4%), and cervicography (56.0%) followed. 2) Specificity : Cervicography was 61.1%, HPV DNA test (45.9%), cytologic test (30.6%), double combined test by cytologic test plus HPV DNA test (22.9%), double combined test by cytologic test plus cervicography (8.3%), and triple combined test (7.9%) followed. 3) PPV : No statistically significant differences were shown among single, double and triple combined tests, and it ranged between 72.2% and 80.8%. 4) NPV : Triple combined test was 100%, double combined test by cytologic test plus HPV DNA test (80.0%), HPV DNA test (68.0%), double combined test by cytologic test plus cervicography (60.0%), and cervicography (34.9%) followed. 5) Efficiency : Larger than 70% of efficiency in all screening methods (either single or combined) except single cervicography (57.4%). 6) FPR : Triple combined test was 92.1%, double combined test by cytologic test plus cervicography (91.7%), double combined test by cytologic test plus HPV DNA test (78.4%), cytologic test (69.4%), HPV DNA test (54.1%), and cervicography (38.9%) followed. 7) FNR : Cervicography was 44.1%, HPV DNA test (8.7%), cytologic test (5.4%), double combined test by cytologic test plus cervicography (2.2%), double combined test by cytologic test plus HPV DNA test (1.1%), and triple combined test (0%) followed. CONCLUSION: Even though the optimal clinical management of cervical cytologic abnormality remains still problematic, this study demonstrates that additional HPV DNA test and/or cervicography have much value in predicting histologic CIN diagnoses. Primary care clinicians can easily perform these tests at their clinics as an intermediate triage criteria to prevent overreferral for colposcopy without compromising the detection of significant disease underlying cytologic atypia.

The Prevalence of HPV Infection in General Population of Korea and Efficacy of HPV DNA Test as an Adjunctive Screening of Cervical Cancer / 대한부인종양콜포스코피학회잡지

OBJECTIVE: Our study was performed to assess prevalence of HPV infections in general female population of Korea and efficacy of HPV DNA test as an adjunctive screening of cervical cancer. MATERIALS AND METHODS: From January 2000 to December 2000, a total 689 patients who had undergone Pap smear and HPV DNA test using Hybrid Capture System-II were included in this study. High risk types of HPV included 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68. We performed colposcopic biopsy on 203 patients. RESULTS: High-risk oncogenic HPV infections were found in the 19.4% of the investigated patients. The sensitivity and negative predictive value of Pap smear alone in identifying the lesions more severe than CIN 2 was 72.2% and 83.2%, respectively. The combination of Pap smear and high risk HPV testing increased to 96.3% and 95.3%, respectively. CONCLUSIONS: The prevalence of HPV infection in general population was 19.4%. The use of HPV DNA testing significantly improved the sensitivity or negative predictive value of the diagnosis of high grade CIN or cancer. Thus, we suggest HPV DNA testing appears to be a needed adjunct to the Pap smear and a combined screening test offers the possibility of greater detection or longer screening intervals, which will be able to reduce the overall cost of the screening program.

Hybrid Capture System HPV DNA Test as a Screening Tool of Cervical Cancer / 대한부인종양콜포스코피학회잡지

OBJECTIVE: Although the use of cytology in screening has reduced morbidity and mortality from invasive cervical cancer, there has been limitation because of the low sensitivity and high false negative rate in the detection of preclinical or clinical disease of the cervix. This study was performed to explore the usefulness of Hybrid Capture System HPV DNA test as a diagnostic method of the cervical cancer. METHODS: Cervical cytology and Hybrid Capture System 1 (HCS1) HPV DNA test were performed in 1,023 women who visited Gynecologic Oncology Clinic in Guro Hospital, Korea University Medical Center. HPV DNA were retested by HCS1, HCS2 and Polymerase Chain Reaction(PCR), in randomly selected 200 women to compare these DNA tests. RESULTS: While the sensitivity and specificity of cervical cytology in detection of cervical lesion were 71.2% and 89.5%, those of HCS1 HPV DNA test were 63.0% and 86.9% respectively. There was significant difference in detection of cervical precancerous lesions between HCS1 and HCS2 (P<0.05), but not between HCS2 and PCR (P=0.14). And the sensitivity and specificity were improved with combining cytology and HCS1 HPV DNA test(82.2%, 86.9%~). CONCLUSION: HCS HPV DNA test may be considered as a useful adjunctive test with cervical cytology in cervical cancer screening.

Natural Course of Low Grade Squamous Intraepithelial Lesion / 대한부인종양콜포스코피학회잡지

OBJECTIVE: The purpose of this project was to suggest guidelines for management of Low grade Squamous Intraepithelial Lesion(LSIL) by evaluating natural course of LSIL of the uterine cervix. MATERIAL & METHODS: Among the women who visited Korea University Kuro Hospital from Jan. 1993 to Oct. 1998, One hundred fifty eight patients who were diagnosed as LSIL with colposcopy directed biopsy were followed up by colposcopy and/or cytology, HPV DNA test every 3 months. RESULT: In I58 patients who were diagnosed as LSIL, colposcopic examination confirmed progression to high grade intraepithelial lesion(HSIL) in 17(10.7%) patients, persistence of LSIL in 87(55%) patients, regression to normal in 54(34.2%) patients during the 3 year follow-up period. In prediction of LSIL subgroup, abnormal Pap test is 39%, 64%, 71% and abnormal HPV test is l6%, 29%, 65% in regression, persistent and progression group respectively. The shortest time of transition from minor lesion(LSIL) to high grade lesion was 12 months (the range, 12-51). CONCLUSION: Of the patients who were diagnosed as LSIL and monitored by colposcopy for 60 months, 34% had disease that regressed, 55% had persistent disease, and 11% had progressive disease. HPV DNA test(p=0.002) is more informative than pap test(p=0.567) in prediction of disease progression.