Human papillomavirus (HPV) belongs to the family Papillomaviridae and is a small molecule, non-encapsulated, circular double-stranded DNA virus with a genome of about 8000 base pairs (bp) and is divided into three Functional regions, namely early transcription region (E region), late transcription region (L region) and non-transcribed region (long control region, LCR). HPV infects humans through direct or indirect contact with contaminated items or sexual transmission. The virus is not only host-specific, but also tissue-specific. It can only infect human skin and mucosal epithelial cells, causing various papilloma or warts of human skin. and reproductive tract epithelial proliferative damage.

       For HPV infecting the genital tract and anus, according to the virulence or carcinogenic risk of each genotype, it can be divided into two categories: low-risk and high-risk. Among women with a sexual life history, genital HPV infection is common. According to statistics, 70% to 80% of women will have at least one HPV infection in their lifetime, but most infections are self-limiting, with more than 90% Infected women develop an effective immune response that clears the infection between 6 and 24 months without any long-term health intervention. Persistent high-risk HPV infection is the main cause of cervical intraepithelial neoplasia and cervical cancer. Global research results show that the presence of high-risk HPV DNA is detected in 99.7% of cervical cancer patients, of which HPV16, 18, 45 and 31 infections account for 80%. Low-risk HPV types are generally associated with condyloma acuminatum or low-grade squamous intraepithelial lesions and rarely cause invasive carcinoma. According to the research results of WHO International Agency for Research on Cancer (IARC) and other international organizations, 13 genotypes including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 are usually listed. It is a high-risk type, and 5 genotypes such as 26, 53, 66, 73, and 82 are classified as medium-risk types. Currently, HPV detection reagents and their requirements on the market are for the intended use related to cervical cancer (the above 18 genotypes). ) HPV genotype nucleic acid detection, usually "high-risk type" basically refers to these 18 HPV genotypes.

         For many years, the international diagnosis of cervical intraepithelial neoplasia and cervical cancer mainly follows the "three-step" diagnostic procedure, namely cervical cytology, colposcopy and histopathology, and the results of colposcopy and histopathology. is the gold standard. Cervical cytology is a commonly used screening method for cervical intraepithelial neoplasia and cervical cancer, which can detect early lesions. High-risk HPV detection is used for triage and cervical cancer screening of patients with abnormal cervical cytology, which can effectively increase the detection rate of cervical lesions, improve the sensitivity of cytology, and reduce the frequency of screening, but cervical cytology also exists its inherent limitations.

         Generally, the human papillomavirus (HPV) nucleic acid detection and genotyping reagents refer to the use of nucleic acid detection technologies including PCR-fluorescent probe method or other molecular biology methods to detect specific high-risk HPV nucleic acids (including DNA and RNA) sequence for the purpose of detection, a reagent for in vitro qualitative detection of human cervical samples (such as human cervical exfoliated epithelial cells or secretions, etc.) virus, or simultaneously identify the genotype of HPV infection. HPV nucleic acid detection reagents refer to reagents that can detect multiple genotypes of HPV at the same time but cannot genotype positive results; HPV genotyping reagents refer to the detection of multiple genotypes of HPV and can genotype HPV positive results simultaneously reagent.

          The clinical significance of HPV testing:

          1). Screening of patients with ASC-US (atypical squamous cells of undetermined significance) results on cervical cytology to determine whether colposcopy is necessary (referred to as ASC-US population shunt use);

          2). For women aged 30 and above, cervical cancer screening should be performed in conjunction with cervical cytology by detecting whether there is high-risk HPV infection. Check the requirements of the guidelines to guide the management of patients (referred to as cervical cancer combined screening purposes);

          3). For women of a certain age group (according to the results of clinical trials), cervical cancer screening is performed by detecting whether there is high-risk HPV infection. This test combines the evaluation of cytological history and other risk factors, and clinical diagnosis and treatment. It is used to guide the management of patients (referred to as the primary screening of cervical cancer).

          The following points need to be emphasized about the intended use of HPV testing products:

         First, in women <30 years old, although the HPV infection rate is high, its spontaneous clearance rate is also high. Therefore, it is not recommended to use HPV testing for combined screening for subjects with normal cytology. HPV detection can also be directly used as a primary screening method on the basis of clinical trials; the applicability of such HPV nucleic acid detection reagents to people of different ages should meet the requirements of relevant cervical cancer screening guidelines.

         2. When the HPV nucleic acid detection reagent is used for ASC-US population triage or cervical cancer screening, the HPV genotypes it can cover should at least include 16, 18, 31, 33, 35, 39, 45, 51, 52, Types 56, 58, 59, and 68 (13 types in total), or one or more of types 26, 53, 66, 73, and 82; according to existing research results, if the detectable HPV gene If the type cannot cover the above 13 high-risk types, it may cause the negative expected value to fail to meet the clinical requirements, so it is not recommended to be used for the above-mentioned intended use alone.

         Third, low-risk HPV is generally associated with condyloma acuminatum or low-grade squamous intraepithelial lesions, but the clinical value of its detection is unclear.

          Fourth, in view of the fact that the sample collection method used for HPV detection is not conducive to the traceability of quantitative values, and the accuracy of quantitative detection results cannot be guaranteed, HPV detection reagents are basically positioned as qualitative detection.

          At present, the existing HPV nucleic acid detection technologies mainly include hybridization capture method, enzyme digestion signal amplification method, PCR-fluorescent probe method, transcription-mediated nucleic acid amplification technology, and PCR-hybridization method and other molecular biology technologies.

          The sample type is human cervical samples. Different sample collection methods may have different sample collection solutions. Different sample collection solutions will affect the minimum detection limit and precision evaluation of HPV detection, as well as the analytical performance of the reagent. Unreasonable sample collection, transport and handling, as well as improper experimental operation and experimental environment may lead to false negative or false positive results. Because of the wide range of cervical cancer screening involved, the risk of potential public health damage caused by false-negative and false-positive HPV test results is significant. False-negative results can lead to untimely cervical cancer diagnosis and treatment; false-positive results can lead to unnecessary frequent screening and invasive treatment. Given that sample collection methods for such products are not easily standardized, the sample collection process is critical to the accuracy of test results. Therefore, it is recommended to use the same cervical epithelial cell sample for cytology and HPV testing to avoid deviations caused by different samples; and the time interval between cervical cell sample collection and colposcopy is not too long, and it is recommended not to exceed 12 weeks. Appropriate nucleic acid isolation/purification steps are required prior to target nucleic acid detection. The purpose of separation/purification is not only to isolate the target nucleic acid in the largest amount, but also to purify it to remove PCR inhibitors as much as possible.

          The clinical significance of HPV nucleic acid detection and genotyping reagents is mainly to provide information on the risk of cervical disease in women, so that clinicians can make more accurate disease judgments and scientific patient management in combination with other test results of patients. The main clinical uses are as follows:

          ￠ù. Screening of patients with ASC-US (atypical squamous cells of undetermined significance) results on cervical cytology to determine whether colposcopy is required (hereinafter referred to as the use of ASC-US population shunt);

          ￠ú. Among women aged <30 years old, the HPV infection rate is high, and the spontaneous clearance rate is also high. Therefore, for this group of people, if the cervical cytology test is normal, the HPV test should not be used for joint screening. It is recommended that only Screening with cervical cytology,

          ￠?. HPV test results should be combined with the results of cervical cytology and other related medical examinations for comprehensive analysis, and should not be used as the basis for patient management alone.

Glossary:

          (1). Atypical squamous epithelial cells of undetermined significance (ASC-US): refers to abnormal squamous epithelial cells whose morphological characteristics and lesion nature cannot be determined.

          (2). Cervical intraepithelial neoplasia (CIN): is a collective term for a group of lesions, including cervical dysplasia and carcinoma in situ, which are precancerous lesions of cervical invasive cancer. Such lesions are still confined to the cervical epithelium without penetrating the basement membrane and without interstitial infiltration.

          The HPV sample collection process is critical to the accuracy of HPV test results. Our company has carried out sufficient research on the collection of HPV samples. The HPV sampling series products produced by our company solve the problem of HPV sample collection methods, and solve the series of problems such as effective collection, scientific transfer and processing of cervical samples, and maximize the preservation of samples. It has its own effectiveness, reduces the difficulty of separation/purification to the greatest extent, and removes PCR inhibitors as much as possible, so that the interference caused by sample collection in the subsequent series of HPV detection operations can be minimized as soon as possible. The HPV sampling series products produced by our company include HPV cervical sampling brushes, sample preservation solutions and other individual product specifications and models, which can meet the basic needs of different customers. At the same time, the TCT liquid-based thin-layer cell preservation solution produced by our company can meet the needs of the same cervical epithelial cell sample for cytological examination and HPV detection at the same time.