The Effect of HPV Vaccine on Menstrual Cycle in Women of Reproductive Age

Premature Ovarian Failure Clinical Trial

Official title:

Research for the Effect of HPV Vaccine on Menstrual Cycle in Women of Reproductive Age

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05838157
• Other study ID #: 2022111615154477
• Status: Recruiting
• Start date: May 4, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2023
• Source: Sun Yat-sen University
• Contact: Juan Xiao, Master
• Phone: 87345515
• Email: xiaojuan[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Cervical cancer is one of the most common cancer in women, making it the fourth largest cause of female cancer mortality worldwide. High-risk HPV types (hrHPV) continuous infection is the main cause of the premalignant and malignant lesions of the cervix. The most effective primary prevention of cervical cancer is administration HPV vaccines. There are three prophylactic HPV vaccines including bivalent HPV (2vHPV)， quadrivalent HPV vaccine (4vHPV)，9-valent HPV vaccine (9vHPV) currently. With the widespread of HPV vaccination， the cases related to abnormal menstrual cycle or menstrual irregularities has gradually increased in the Vaccine Adverse Event Reporting System, also the number of reports and studies were increasing. We designed this study to evaluate the statistical association of HPV vaccine and changes in menstrual cycle or menstrual irregularities、amenorrhea. And detect the signal of premature ovarian insufficiency (POI) and related events of three HPV vaccines, and to provide evidence for the safety of HPV vaccines based on the data mining and signal detection method. The research data was obtained from prospective self- developed questionnaire. Before-after study was applied in this study, investigators collect the menstrual cycle data of subjects by the questionnaire and qualitatively interview were taken. The control group is before vaccination, HPV vaccination is Intervention group.

Description:

High-risk HPV types (hrHPV) continuous infection is the main cause of the premalignant and malignant lesions of the cervix. The most effective primary prevention of cervical cancer is administration HPV vaccines. There are three prophylactic HPV vaccines including bivalent HPV (2vHPV)， quadrivalent HPV vaccine (4vHPV)，9-valent HPV vaccine (9vHPV) currently. With the widespread of HPV vaccination， the cases related to abnormal menstrual cycle or menstrual irregularities has gradually increased in the Vaccine Adverse Event Reporting System, also the number of reports and studies were increasing. Whereas all of the studies are retrospective and the data from passive surveillance system, meanwhile, HPV vaccines has been available in Chinese mainland less than 7 years. Especially, 9vHPV applicable range was broadened to 45 years shortly before. There are rarely prospective researches focus on the connection between HPV vaccines and menstrual disorder. We designed this prospective study to observe and evaluate the statistical association of HPV vaccine and menstrual disorder such as menstrual irregularities、amenorrhea、 hypomenorrhea or hypermenorrhea in Chinese women. And detect the signal of premature ovarian insufficiency (POI) and related events of three HPV vaccines, and to provide evidence for the safety of HPV vaccines based on the data mining and signal detection method.

The study design used self-control, We using a self-designed questionnaire collect the menstruation data of girls and women aged 16 to 40 years who receiving HPV vaccination ( including 2vHPV、4vHPV、9vHPV) in Cancer Prevention Center, Sun Yat-sen University Cancer Center during May 10th 2023 to April 30th 2023. The self-designed questionnaire contains three parts. First part includes personal basic information such as age, profession, education Level, marital or childbearing status etc. Part two there are containing health status, menstruation conditions (include menstrual cycle, menstrual period, menstrual blood volume and dysmenorrhea etc). Part three collects menstruation conditions by qualitatively interview , covers each menstrual cycle after the first dose of HPV vaccination until 3 months after the third dose .

To analyze the data, R studio statistical software was used. The general measurement data were analyzed by paired sample T test, p=0.05. Bayesian trusted Propagation neural network (BCPNN) and multi-item gamma Poisson contractor (MGPS) were used to detect the signals of POI related events and to conduct empirical Bayes data mining among ours database.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 40 Years

Eligibility

Inclusion Criteria:

• Previous menstrual cycles were regular and normal

• At least one vaccination of HPV vaccine

Exclusion Criteria:

• Pregnancy

• Breast-feeding

• Record of abnormal results of HPV test/ cervical cytology/ gynecological ultrasonography

• Record of medications related to menstruation

• Diseases contribute to menstrual irregularities?amenorrhea such as severe anemia/ coagulation disorders/ thyroid dysfunction etc.

• Participation in other clinical trials

Related Conditions & MeSH terms

• Menopause, Premature
• Menstrual Disorder
• Menstruation Disturbances
• Premature Ovarian Failure
• Primary Ovarian Insufficiency

Intervention

Biological:
• prophylactic HPV vaccine(bivalent HPV?quadrivalent HPV?9-valent HPV)
at least one dose of prophylactic HPV vaccine including bivalent HPV (2vHPV), quadrivalent HPV vaccine (4vHPV),9-valent HPV vaccine (9vHPV)

Locations

Country	Name	City	State
China	Cancer Prevention Center,Sun Yat-sen University Cancer Cente	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Cente	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

References & Publications (8)

Colafrancesco S, Perricone C, Tomljenovic L, Shoenfeld Y. Human papilloma virus vaccine and primary ovarian failure: another facet of the autoimmune/inflammatory syndrome induced by adjuvants. Am J Reprod Immunol. 2013 Oct;70(4):309-16. doi: 10.1111/aji.1 — View Citation

de Sanjose S, Delany-Moretlwe S. HPV vaccines can be the hallmark of cancer prevention. Lancet. 2019 Aug 10;394(10197):450-451. doi: 10.1016/S0140-6736(19)30549-5. Epub 2019 Jun 26. No abstract available. — View Citation

Gong L, Ji HH, Tang XW, Pan LY, Chen X, Jia YT. Human papillomavirus vaccine-associated premature ovarian insufficiency and related adverse events: data mining of Vaccine Adverse Event Reporting System. Sci Rep. 2020 Jul 1;10(1):10762. doi: 10.1038/s41598 — View Citation

Hviid A, Myrup Thiesson E. Association Between Human Papillomavirus Vaccination and Primary Ovarian Insufficiency in a Nationwide Cohort. JAMA Netw Open. 2021 Aug 2;4(8):e2120391. doi: 10.1001/jamanetworkopen.2021.20391. — View Citation

Little DT, Ward HR. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination: A Case Series Seen in General Practice. J Investig Med High Impact Case Rep. 2014 Oct 28;2(4):2324709614556129. doi: 10.1177/2324709614556129. eColl — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caa — View Citation

Tatang C, Arredondo Bisono T, Bergamasco A, Salvo F, Costa Clemens SA, Moride Y. Human Papillomavirus Vaccination and Premature Ovarian Failure: A Disproportionality Analysis Using the Vaccine Adverse Event Reporting System. Drugs Real World Outcomes. 202 — View Citation

Torella M, Marrapodi MM, Ronsini C, Ruffolo AF, Braga A, Frigerio M, Amabile E, Vastarella MG, Rossi F, Riemma G. Risk of Premature Ovarian Insufficiency after Human Papilloma Virus Vaccination: A PRISMA Systematic Review and Meta-Analysis of Current Evid — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of the menstrual cycle	In 16~40 years old women , any frequency shorter than 21 days or longer than 36 days will be defined as abnormal	3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
Primary	Duration of the menstrual cycle	In 16~40 years old women , any duration shorter than 3 days or longer than 7 days will be defined as abnormal	3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
Primary	Quantity of the menstrual cycle	In 16~40 years old women , any quantity less than 30 ml or more than 80 ml will be defined as abnormal	3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
Secondary	Premature ovarian failure (POF) signals	From the first dose of the vaccine, Blood biochemical detection used to measure the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T) and prolactin (PRL). And Ultrasonography is used to detected changes in the endometrium after each vaccination.	3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)