Clinical trial NCT05838157: The Effect of HPV Vaccine on Menstrual Cycle in Women of Reproductive Age
Official title: Research for the Effect of HPV Vaccine on Menstrual Cycle in Women of Reproductive Age
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Menstrual Disorder
Premature Ovarian Failure
Keywords: HPV vaccine
menstrual cycle
menstrual disorder
premature ovarian insufficiency
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2023-05-01
Enrollment: 600
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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 April 10th 2023 to April 30th 2023.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of the menstrual cycle
timeFrame: 3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
measure: Duration of the menstrual cycle
timeFrame: 3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
measure: Quantity of the menstrual cycle
timeFrame: 3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
Secondary outcomes:
measure: Premature ovarian failure (POF) signals
timeFrame: 3 months after the administration of the third dose of vaccine( starts with the first dose of HPVvaccine, no less than 9 cycles)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Cancer Prevention Center,Sun Yat-sen University Cancer Cente
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Cente
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Juan Xiao, Master
role: STUDY_DIRECTOR
affiliation: Sun Yat-sen University
name: Chuanbo Xie, PhD
role: STUDY_DIRECTOR
affiliation: Sun Yat-sen University
name: Junjie Chen, Bachelor
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-sen University
name: Huiping Ye, Bachelor
role: PRINCIPAL_INVESTIGATOR
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