| Cervical cancer (CC) is common malignant tumor in female worldwide, seriously endangering the health of women. It has been recognized that persistent infection of high-risk human papillomavirus (HR-HPV) is necessary cause of cervical carcinogenesis. But the progressions for HR-HPV-infected women from cervical intraepithelial neoplasia (CIN) to invasive cervical cancer (ICC) are about 5-20 years. This provides opportunities for diagnoses and treatments of CC and its precancerous lesions. Effective screenings and early diagnoses during this period can damatically curb the development of CC and reduce its morbidity and mortality.Cytology is the most commonly used screening method in CC. Because of its timesaving and low-cost, it still plays an important role as a routine screening program in many countries nowadays. However, the cytological result is not very reliable and has a high false negative rate, usually needs a repeat test in order to obtain satisfactory sensitivity. When to cervical adenocarcinoma, the sensitivity is much lower than in squamous cell carcinoma. Though emergences of new technologies such as thinprep cytology test (TCT) had improved cytology, but did not completely change the status of its low sensitivity, which restricted the development of cytology screening. HPV test is another important screening method for CC. In some European countries, HPV test is now replacing cytology, to become the first choice for the screening of cervical lesions. HPV test is more effective than cytology in large population screening, and its high sensitivity can help to concentrate people into high-risk groups. But the problem remains that HPV infection is very common, the accumulative infection rate of a sexual adult in life is probably 80%. The infection is usually transient, that can be promptly eliminated by immune system and does not lead to high-grade CIN or CC. Therefore, HPV test usually has a high false positive rate, especially among young women.So it is necessary to find new means to replace or assist the regular methods, to make the screening of CC and its precursors more accurate, reliable and predictive. Many studies had shown that gaining of chromosome 3q is common during the transition from high-grade CIN to ICC. Analysis on their hotspot regions suggested that telomerase RNA component (TERC) located in 3q26.3 may be the most important gene. Gain of TERC could block apoptosis, leading to tumorigenesis, and might be an early event in cervical carcinogenesis. Many scholars had studied the expression of TERC in different cytological and histological gradings. However, the role of TERC in CC screening and the correlations among TCT, HR-HPV and TERC still need a systematic research.In this study, we applied fluorescence in situ hybridization (FISH) to detect the expression of TERC in cervical exfoliated cells among different groups. Then using histopathology as the gold standard, we compared TERC results with cytology and HPV test findings, to assess the role of TERC in the screening of CC and its precancerous lesions. Objectives:To evaluate the expression of TERC by FISH, and to explore the value of TERC as a primary screening method of squamous cervical cancer and its precursors.Methods:A total of 201 TCT specimens were collected from outpatient. All participants underwent cytology, HR-HPV HC2, TERC FISH, colposcopy examination and biopsies with histopathological diagnoses if necessary. TERC expressions in different cytological, HR-HPV and histopathological gradings were analyzed. Then using≥CIN2 as the reference standard, cytology, HR-HPV HC2 and TERC FISH, the three different screening methods were compared. Finally, the feasibility of TERC FISH as a primiary screening method for squamous cervical cancer and its precursors was assessed. Statistical analysis was performed usingχ2 test or Fisher's exact test.Results:1. The positive expression rates of TERC in NILM, ASC-US, LSIL, ASC-H and HSIL were 2.83%,17.39%,37.50%,62.96% and 90.48%, respectively. Significant difference was observed between groups≤LSIL and>ASC-H (P<0.001).2. The positive expression rates of TERC in HR-HPV negative and positive groups were 4.85% and 47.96%, respectively, and significant difference was observed between groups (P<0.001).3. The positive expression rates of TERC in normal, CIN1, CFN2, CIN3 and squamous cell carcinoma (SCC) were 6.06%,10.00%,66.67%,72.50% and 100.00%, respectively. Significant difference was observed between groups≤CIN1 and≥CIN2(P<0.001).4. In the comparison of three different screening methods, the sensitivity and NPV of TERC and cytology were equivalent, both lower than HR-HPV. But the specificity, PPV, and accuracy of TERC were superior to cytology and HR-HPV (P<0.05).Conclusions:1. The expressions of TERC about cervical squamous lesions are in good consistency with cytological, histopathological gradings and HPV test findings.2. TERC FISH could be a specific and accurate means applied in the primary screening of squamous cervical cancer and its precursors. Objectives:To evaluate the value of TERC as a triaging method in the prediction of squamous cervical cancer and its precursors.Methods:In the triage of cytology groups, a total of 376 TCT specimens were collected with a diagnosis of either ASC-US or LSIL (including 242 cases of ASC-US, and 134 cases of LSIL). In the triage of HR-HPV positive group, a total of 177 TCT specimens were collected with positive HR-HPV HC2 results. In the triage of HR-HPV positive mild to moderate cytology abnormalities, a total of 300 HR-HPV positive TCT specimens were collected, with a diagnosis of either ASC-US, LSIL or ASC-H (including 129 cases of ASC-US,82 cases of LSIL, and 89 cases of ASC-H). All participants underwent cytology, HR-HPV HC2, TERC FISH, colposcopy examination and biopsies with histopathological diagnosis if necessary. Using≥CIN2 as the reference standard, the sensitivity, specificity, PPV, NPV and accuracy of TERC in different groups were calculated and compared with other triaging methods. Statistical analysis was performed usingχ2 test, Fisher's exact test, analysis of variance or unconditional logistic regression.Results:1. In the triageing of ASC-US, the advantage of HR-HPV in sensitivity still existed (97.73%), while TERC had prominent specificity and accuracy (90.40% and 87.19%).In the triaging of LSIL, TERC had higher specifivity and accuracy than HR-HPV (P<0.001), besides similar sensitivity and NPV with it. 2. In the triaging of HR-HPV positive group, more specimens were still needed. Our current data showed that the sensitivity of TERC was superior or at least similar to cytology (83.33% vs.50.00%, P=0.545), while they had no difference in specificity (P=0.336).3. In the triaging of HR-HPV positive mild to moderate cytology abnormalities, the results of TERC were satisfied. It had sensitivities of 81.82%,83.33%,91.94%, specificities of 93.46%,91.37%,88.89%, and accuracies of 91.47%,89.02%, 91.01%, respectively, in predicting CIN2+in ASC-US, LSIL and ASC-H groups. No difference was observed in sensitivity, specificity and accuracy of TERC among different cytology, HR-HPV viral load and age groups. When lesion levels rose, the average positive nuclei ratio of TERC increased.Conclusions:1. HR-HPV has higher sensitivity, but TERC has better specificity and accuracy in the triage of ASC-US. While in LSIL triage, TERC could be an effective means.2. TERC is supposed to be an alternative second triage besides cytology in HR-HPV positive group, with better or at least similar sensitivity and specificity with cytology.3. In the triage of HR-HPV positive mild to moderate cytology abnormalities, TERC could be a sensitive, specific and stable triaging method. Objectives:To evaluate the adjunct diagnostic value of TERC in abnormal glandular cells findings of cytology.Methods:A total of 35 TCT specimens with abnormal glandular cells findings were collected from outpatient (including 19 cases of AGC-NOS,9 cases of AGC favor neoplasia, and 7 cases of adenocarcinoma). All participants underwent HR-HPV HC2, TERC FISH, ECC, colposcopy examination and biopsies with histopathological diagnoses. TERC expressions in different cytological and histopathological gradings were analyzed, and the feasibility of TERC FISH as a screening method in predicting cervical adenocarcinoma was assessed. Statistical analysis was performed using x2 test or Fisher's exact test.Results:1. The positive expression rates of TERC in AGC-NOS, AGC favor neoplasia and adenocarcinoma were 36.84%,88.89%, and 100.00%, respectively. Significant difference was observed between groups AGC-NOS and> AGC-NOS (P=0.047).2. The positive expression rates of TERC in cervical AIS and invasive adenocarcinoma were both 100.00%.Conclusions:TERC expressions are in good consistency with cytological and histopathological gradings, and may have adjunct diagnostic value in abnormal glandular cells findings of cytology. |
PDF Full Text Request