Telomerase activity in Papanicolaou smear-negative exfoliated cervical cells and its association with lesions and oncogenic human papillomaviruses

OBJECTIVE: The goal of this study was to evaluate telomerase activity in exfoliated cervical cells and its association with cytology, pathology, and human papillomavirus (HPV). METHODS: Telomerase activity and HPV DNA sequences were examined in the exfoliated cervical cells from a general population of 245 women aged more than 30 years undergoing routine cervical screening by Papanicolaou smear. The women who were found to have telomerase activity or abnormal cytology in their exfoliated cervical cells were examined for cervical lesions by colposcopy and biopsy. RESULTS: Cytology for our population (mean, 56 years) revealed only one abnormal smear (1/245, 0.4%), in which a cervical intraepithelial neoplasia grade I (CIN I) lesion was found. The exfoliated cervical cells used to prepare the smear were negative for telomerase and contained low-risk HPV DNA. Telomerase activity was found in 16 exfoliated cell samples (16/245, 6.5%); high-risk HPV DNA was found in 9 of these samples (9/16, 56%) and 9 of the biopsy specimens that could be evaluated from patients testing positive for telomerase revealed CIN I lesions (9/11, 82%). CONCLUSIONS: Telomerase activity is often associated with high-risk HPV infection and it is suggested that telomerase assay can help to detect occult cervical lesions.     

Telomerase activity in the vaginal margins of radical hysterectomy in patients with carcinoma of the cervix: correlation with histology and human papillomavirus

This study was undertaken to evaluate the telomerase activity both in the tumor and in the vaginal margins of radical hysterectomy in patients with squamous cell carcinoma (SCC) of the cervix. Thirty-three patients with SCC of the cervix (study group) and 13 patients with uterine myoma (control group) were prospectively studied. Tissue samples were taken from the tumor or cervix, anterior vaginal margin (AVM), and posterior vaginal margin (PVM). The specimens were analyzed by histopathology, by a telomerase PCR-TRAP-ELISA kit, and by polymerase chain reaction using human papillomavirus (HPV) DNA. The telomerase activity was significantly higher in the tumor than in the benign cervix (P < 0.001). There was no difference in telomerase activity in the AVM and PVM in patients with cervical carcinoma compared to the control group. Telomerase activity was associated with the presence of histologic malignancy in the PVM of patients submitted to radical hysterectomy (P= 0.03). This association was not observed with the presence of HPV in AVM or PVM in the study group. Telomerase activity is a marker of histologic malignancy in patients with SCC of the cervix. There was no association between the telomerase activity and the presence of HPV in vaginal margins of patients submitted to radical hysterectomy.     

Screening of premalignant cervical lesions for HPV 16 DNA by sandwich and in situ hybridization techniques

A series of 97 cervical smears and 69 directed punch biopsies derived from 84 consecutive women prospectively followed-up for cervical HPV (human papillomavirus) infections were studied using the sandwich hybridization and in situ hybridization techniques with HPV 16 DNA probes. The aim was to test the sensitivity and applicability of these two techniques in routine diagnosis of cervical HPV infections from smears. As a measure of specimen adequacy, the number of cells recovered in the cervical scrape was determined along with HPV 16 DNA in the sandwich hybridization test using human pro-alpha 2(I)-collagen gene probe. CIN (cervical intraepithelial neoplasia) was suggested in 56% of the patients by the Pap smear, and disclosed in 65% of the biopsies. HPV 16 DNA was present in 57% of cervical scrapes consistent with CIN, i.e., were of Pap smear classes III or IV. Forty percent of the scrapes not suggestive of CIN, i.e., Pap smear classes I or II, also contained HPV 16 DNA. The detection rate for HPV 16 DNA of the sandwich hybridization method was 89% of that of the in situ method in adequate scrapes, but only 43% in cell-poor specimens. The number of HPV 16 DNA-positive scrapes as compared with the total number of diagnoses obtained by studying also the biopsies was 31/36 (69 patients). The results indicate that the cervical scrape as a noninvasive specimen is applicable for screening of cervical HPV infections, and it can be studied with acceptable sensitivity by the rapid sandwich hybridization technique. However, if a punch biopsy is indicated it should be studied using the in situ hybridization technique that allows more sensitive detection of HPV DNA than any other hybridization method and enables the analysis of several HPV types in the same sample instead of only one HPV type in the scrapes.     

Antibodies to human papillomavirus 16 L1 virus-like particles as an independent prognostic marker in cervical cancer

OBJECTIVE: Infection with high-risk human papillomavirus (HPV) types such as HPV-16 is a major risk factor for the development of cervical cancer. HPV-16 capsid antibodies are detectable in approximately 50% of patients with HPV-16 DNA-positive cervical cancer. We investigated the prognostic significance of HPV capsid antibodies for survival in patients with cervical cancer in comparison with conventional clinicopathologic features such as staging, histologic grading, histology, age, and treatment modality. STUDY DESIGN: Serum samples from 68 patients with cervical cancer and 65 healthy female control subjects were analyzed by enzyme-linked immunosorbent assay for HPV-specific immunoglobulin G (IgG) antibodies to baculovirus expressed HPV-6, HPV-11, HPV-16, and HPV-18 L1 virus-like particles (VLPs). RESULTS: HPV-16 L1 IgG antibodies were detectable in 6 of 65 (9%) of the control subjects and in 19 of 68 (28%) of the patients with cervical cancer (P =.007). In the subgroup of patients with HPV-16 DNA-positive cervical cancer (comprising 50% of the investigated samples), HPV-16 L1 antibodies were detected in 40%. HPV-16 L1 seropositivity was in univariate and multivariate analysis in addition to International Federation of Gynecology and Obstetrics stage, the only independent positive prognostic factor for overall survival (P =.01). CONCLUSION: Antibodies to HPV-16 L1 were found to be an independent prognostic factor for overall survival in patients with cervical cancer. Thus, HPV-16 infection may be involved not only in oncogenesis but also in tumor development and behavior.     

Detection and quantitation of human papillomavirus type 16, 18 and 52 DNA in the peripheral blood of cervical cancer patients

OBJECTIVE: To prospectively evaluate the feasibility of detecting human papillomavirus (HPV) type 16, 18 and 52 DNA in the peripheral blood of patients with cervical cancer using real-time polymerase chain reaction (PCR) and to determine its prognostic importance. METHODS: Blood and cervical swab specimens from 135 consecutive patients with 60 invasive cervical cancers, 10 microinvasions, 20 cervical intraepithelial neoplasias (CIN) III, 10 CIN II, 10 CIN I and 25 controls were collected and examined for HPV type 16, 18 and 52 DNA using real-time PCR to investigate the prevalence and viral load of HPV DNA at the time of diagnosis and during follow-up in patients with positive blood samples. RESULTS: Of the 60 patients with invasive cervical cancer, 27% had positive test results for HPV DNA in blood samples in contrast to 0% of patients with microinvasions, CIN III, CIN II, CIN I and normal controls. The DNA detection rates of viral subtypes in blood samples of cervical cancer patients were 5% for HPV-16, 16.7% for HPV-18, 8.3% for HPV-52, 1.7% for both HPV-16 and HPV-18 and 1.7% for both HPV-18 and HPV-52, while the detection rates in cervical swab specimens were 36.2% for HPV-16, 15.5% for HPV-18 and 17.2% for HPV-52. During follow-up, 8 of 10 cervical cancer patients with viral DNA detected in blood within 3 months after treatment had recurrence, and a high percentage (87.5%, 7/8) of this recurrence involved distant metastases. CONCLUSIONS: In this study, real-time PCR detected HPV-16, -18 or -52 DNA in the peripheral blood of more than one-fourth of invasive cervical cancer patients. The association between risk of cancer recurrence and the amount of viral DNA detected in blood among cervical cancer patients after treatment is intriguing and deserves further investigation.     

The relationship of human papillomavirus (HPV) detection to pap smear classification of cervical-scraped cells in asymptomatic women in northeast Thailand

OBJECTIVE: To correlate the detection of human papillomavirus (HPV) with the Pap smear classification of cervical-scraped cells from asymptomatic women living in northeast Thailand. METHODS: A total of 260 asymptomatic women attending the Obstetrics and Gynecology's Outpatient Clinic, Srinagarind Hospital, Thailand, were interviewed for risk factors and cervical scrapes were taken. The cells were examined by Pap smear for cytological changes and by PCR for HPV DNAs--nononcogenic (HPVs 6 and 11) and oncogenic (HPVs 16, 18 and 33) types. Cervical biopsies were taken from women with abnormal Pap smears for histological examination. RESULTS: Of the 260 cervical smear samples, the cervical cells were classified as normal and abnormal in 174 and 86, respectively. Twenty-three percent of all samples were positive for overall HPV DNA. HPV DNAs (mostly HPVs 6 and 11) were detected in 21% of normal cells, and the higher detection rate (27%) for HPV DNA in abnormal cells gradually increased in severity from 16% in Class 3 to 35 and 60% in Classes 4 and 5, respectively. Histologically 46, 90 and 100% of HPV detection was associated with CIS, SCC and adenocarcinoma, respectively. Almost all of the HPV DNAs detected were types 16, 18 or 33. There was no significant association between HPV infection and reproduction history, sexual behavior and demographic variables. CONCLUSION: We speculated that an abnormal Pap smear and the detection of an oncogenic type HPV may indicate the presence of neoplastic cells in asymptomatic woman who might be at risk for the development of cervical cancer.     

新一代杂交捕获技术在宫颈癌筛查中的应用

目的:了解新一代杂交捕获技术(DH2)在宫颈癌筛查与传统筛查方式的优势比较,探讨HPV16/18分型检测对DH2初筛阳性患者分流管理的临床意义。方法:2013年、2014年、2015年分别对浙江省慈溪市79847例、81702例、61072例妇女采用巴氏涂片的方法进行宫颈癌筛查,在2015年、2016年分别对浙江省慈溪市35657例、59634例妇女使用DH2检测14种高危型HPV的方法进行宫颈癌筛查。以病理诊断作为金标准,分析高危型HPV检测与巴氏涂片在LSIL以上病变的检出率情况。同时对DH2阳性患者进行HPV16/18检测,对照和比较HPV16/18分流策略的检出情况。结果:2013年、2014年、2015年采用巴氏涂片的方法对LSIL以上病变的检出率分别为0.048%、0.105%、0.134%;2015年、2016年使用DH2检测14种高危型HPV的方法对LSIL以上病变的检出率分别为0.415%、0.550%。2015年采用DH2检测14种高危型HPV初筛模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为4.644%、15.370%;2016年采用DH2检测14种高危型HPV初筛及初筛阳性患者HPV16/18分流的模式,LSIL以上病变在DH2阳性及在HPV16/18阳性中的占比分别为6.365%、22.430%。结论:使用DH2检测14种高危型HPV的方法比传统巴氏涂片对LSIL以上病变的检出率更高,DH2可作为宫颈癌初筛的可行方法;DH2初筛及初筛阳性患者HPV16/18分流管理模式对宫颈癌高危人群进行风险分层管理,重点关注HPV16/18阳性人群,可以进一步提高宫颈癌筛查中的LSIL以上病变检出率。     

Prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma and its precursors in Scottish patients

Our aim was to determine the prevalence of human papillomavirus (HPV) types 16 and 18 in cervical adenocarcinoma (and its precursors) in Scottish patients. Nucleic acid was extracted from paraffin-embedded, formalin-fixed tissues. We examined 119 cases of invasive adenocarcinoma, 20 cases of adenocarcinoma in situ, and 16 cases of normal glandular epithelium. HPV DNA was detected by polymerase chain reaction using type-specific primers for the E6 and E7 genes of HPV-16 and HPV-18 with conformation of HPV genotype by subsequent restriction fragment length polymorphism. HPV DNA was identified in 87 (62.6%) cases, with HPV-16 being detectable in 65 (47%) cases and HPV-18 in 41 (29%) cases. All the cases of normal tissue tested negative for HPV-16 and/or HPV-18. No significant relation between infecting HPV type (16 or 18) and subtypes of disease (within the invasive category and between the preinvasive and the invasive categories) was noted. Our findings support that HPV-16, along with HPV-18, are likely to play a significant role in the pathogenesis of cervical adenocarcinomas and that cervical cancer screening strategies that incorporate oncogenic HPV testing, and prophylactic vaccines that target these types, will be beneficial for the reduction of adenocarcinoma and associated glandular precursors.     

Relationship between telomerase activation and HPV 16/18 oncogene expression in squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix.

SILs (squamous intraepithelial lesions) comprise a wide spectrum of clinically and biologically heterogeneous lesions ranging from benign proliferations to precancerous lesions. Telomerase activation plays a critical role in cellular immortalization and might be important for malignant progression. The viral oncogenes E6 and E7 are the principal transforming genes of high-risk HPVs and are important in HPV-associated immortalization and neoplastic transformation. In this study we investigated the relationship between telomerase activity, telomerase RNA, and HPV 16/18 oncogene expression in low- and high-grade SILs and SCCs (squamous cell carcinomas) of the cervix uteri. Telomerase activity was examined by the TRAP-assay and expression of the telomerase RNA (hTR) and HPV 16/18 E6/E7 oncogenes by RNA/RNA-in situ hybridization (ISH). The associated HPV-type was determined by PCR. Telomerase activity was observed in 25/29 (86%) SCCs, 31/41 (76%) high-grade SILs, 6/14 (43%) low-grade SILs, and 1/28 (3.6%) normal cervical tissues. Expression of hTR and viral oncogenes increased significantly with histopathologic severity of the lesion (p < 0.0001). A correlation was found between telomerase activity and intensity of viral oncogene expression. These findings suggest that telomerase activation occurs early in cervical carcinogenesis and is predominantly found in high-grade SILs and cervical SCCs. Our findings support current experimental data that suggest that telomerase is at least partially activated by viral oncogenes of high-risk HPV types. Telomerase activity with concomitant strong viral oncogene expression might therefore characterize a subset of lesions that are at risk for malignant progression.     

Prospective serial study of viral change in the cervix and correlation with human papillomavirus genome status.

OBJECTIVE--To observe in serial fashion the histological changes of human papilloma virus (HPV) infection of the cervix and to correlate these with the detection of HPV genomes. DESIGN--A prospective longitudinal study to perform colposcopy and at 0, 9 and 18 months to obtain a smear, a biopsy for histology and HPV-16 genome detection by DNA/DNA hybridization. SETTING--Glasgow Family Planning Centre. SUBJECTS--Eighty-two women recruited on the basis of a routine smear showing viral change without dyskaryosis. INTERVENTIONS--Women found to have CIN 3 were treated with laser. MAIN OUTCOME MEASURES--Cytology and cervical biopsy results and HPV-16 DNA detection by Southern blotting obtained serially from individual subjects. RESULTS--Of 82 women recruited, 10% were positive for HPV-16 detection by Southern blotting. Detection of HPV-16 genomes did not correlate with either CIN or viral infection assessed histologically and serial hybridizations in a given individual showed fluctuation in HPV-16 detection. Polymerase chain reaction in a subset of samples revealed 46% positive for HPV DNA. CONCLUSION--No clear correlation exists between HPV genome detection and the histological appearance. HPV-16 genome detection alone may not be a useful predictor of precancerous progression.     

Diagnostic value of telomerase activity in gynecologic malignancies

Nagai N, Murakami J, Oshita T, Ohama K, Tahara H. Diagnostic value of telomerase activity in gynecologic malignancies. Int J Gynecol Cancer 1998; 8 : 481–488.
We investigated the diagnostic significance of telomerase activity in gynecological malignancies. Tissue samples were obtained from 24 cervical cancers, 27 uterine cancers (22 endometrial cancers and five sarcomas), 33 ovarian cancers (31 epithelial tumors and 2 germ cell tumors), and 11 benign ovarian tumors. In addition, cervical cytology specimens were obtained from 30 squamous intraepithelial lesions (13 low grade and 17 high grade), and from 22 normal females. Telomerase activity was detected using the TRAP assay, and the relative telomerase activity was obtained using the BioMax DNA image analysis system. Telomerase activity was detected in 22/24 (91.7 %) cervical cancers, 23/27 (85.2%) uterine tumors and 30/33 (90.9%) ovarian cancers. Weak telomerase activity was detected in two mature cystic teratomas and also found in 9/17 (52.9%) high grade SIL and 2/13 (15.4%) low grade lesions. Telomerase activity showed no relationship with tumor histology or clinical stage, and there was no statistically significant difference between patients with uterine cancer and ovarian cancer. Relative telomerase activity showed a correlation with the dilution assay, and significantly higher telomerase activity was found in uterine cervical cancer compared with precancerous lesions and in ovarian cancer compared with benign ovarian tumors. After establishment of an assay for telomerase, it may be useful for cancer diagnosis and identification of high-risk groups.     

HPV genotyping from invasive cervical cancer in Chile

Objective

To determine the prevalence rates of the different HPV types in cervical cancer lesions in Chile to facilitate the development of prophylactic human papillomavirus (HPV) vaccines effective for that country.

Method

Biopsy samples of 312 cervical cancer lesions were assessed for HPV type by reverse-line blotting assay.

Results

HPV DNA was found in 94.2% of the lesions, 67.2% harboring 1 viral type and the remainder harboring more than 1 type. HPV-16 was the most frequent type in single infections (50.5%), followed by HPV-18 (7.8%), HPV-31 (2.4%), and HPV-45 (2.0%). HPV-16 was also present in 98.7% of dual and multiple infections, its most frequent association being with HPV-18.

Conclusions

HPV types 16, 18, 31, and 45, alone or combined with other types, were observed in the biopsy samples of up to 80.5% of cervical cancer lesions.     

Telomerase activity in HPV-associated vulvar vestibulitis

OBJECTIVE: To find a possible correlation between telomerase activity, mean telomere length and human papillomavirus (HPV) presence and type in vulvar vestibulitis. STUDY DESIGN: Twenty-two tissues excised during surgery for the treatment of severe vulvar vestibulitis and nine control tissue samples were tested for telomerase activity, mean telomere length, and HPV presence and type. RESULTS: Thirty-six percent of the tissues from vestibulitis patients were infected with HPV, mainly type 16/18, and none of the control tissue samples showed presence of HPV DNA (P < .02). Telomerase activity was detected in all tissues harboring HPV DNA, whereas only 64% of tissues without HPV DNA exhibited telomerase activity (P < .02). The mean telomere length was unchanged as compared to control samples. CONCLUSION: Telomerase activity in vestibulitis may be increased as a result of HPV infection, suggesting that HPV infection may play a role in the etiology of some cases of vulvar vestibulitis.     

Human papillomavirus (HPV) DNA detection in self-collected urine

OBJECTIVE: Non-invasive sampling of human genitals to identify high-risk individuals with subclinical oncogenic HPV infection remains a challenge. The study was designed to see if self-collected urine can be used as a simple, non-invasive sampling for screening HPV, particularly for screening/monitoring general population or young adolescents or infants, if they are to be immunized by HPV vaccines. METHOD: Self-collected urine samples from 100 sexually unexposed college going girls and cervical scrapes from 104 normal healthy sexually active married women were used in this study. Additionally, a group of 55 women were recruited for collecting first urine and later scraped cervical cells to validate urine sampling by directly comparing HPV positivity between the two types of biological specimens. A dry 'paper smear' method for specimen collection and a simple single tube protocol was employed for PCR detection of HPV infection. RESULTS: Out of 100 sexually inexperienced college going girls, only 6 (6%) were positive for HPV infection as revealed by L1 consensus primer and 4 (4%) of them were positive for HPV 16 but none was found positive for HPV 18 DNA. Out of 104 sexually active married women who were cytologically reported as negative by Pap test, 11 (10.5%) were found HPV positive and 7 (6.7%) of them had infection of high-risk HPV type 16. Both urine and later cervical scrapes from a group of 55 women collected as dry 'paper smear' showed perfect matching positivity for HPV between urine and cervical scrape. CONCLUSIONS: The use of urine coupled with its dry collection as 'paper smear' facilitating their easy transport, storage and direct PCR detection of HPV DNA opens up an alternative non-invasive approach for population screening of HPV infection, at least in such cases as children and infants in whom invasive samples are difficult to obtain.     

Human papilloma virus (HPV) infection and its relationship with central intra-epithelial neoplasia (CIN)

HPV (Human papillomavirus) infection is strongly associated and is the main cause of cervical cancer. The main target for HPV viruses is the cervical transformation zone. In our work infection with HPV 18 and HPV 16 as also other types of viruses were investigated in 15 patients by taking biopsies. Before hand the patients were signalized by cytology as well as all of them were colposcopically examined. The samples were examined immunohistochemically in the laboratory at the Specialized Hospital for Active Treatment in Oncology. Nine out of 15 patients /60%/ were found positive for HPV-16, five /33%/ were found positive for HPV-18 and 1 /6.6%/ were infected with both HPV types. Our method is very sensitive and practical for determining at very high risk of developing HPV connected cervical cancer.     

Presence of Oncogenic HPV DNAs in Cervical Carcinoma Tissues and Pelvic Lymph Nodes Associating with Proliferating Cell Nuclear Antigen Expression

The presence of oncogenic HPV DNAs (HPV-16/18) in cervical carcinomas and their normal and metastatic pelvic lymph nodes and the expression patterns of proliferating cell nuclear antigen (PCNA) in cervical carcinomas were retrospectively studied to elucidate the possible roles of them in malignant transformation and progression of the disease. HPV-16/18 DNAs were detected by polymerase chain reaction using HPV E6 type-specific primers in 79 patients with cervical cancer: 31 patients who had pelvic lymph node metastasis (group I) and 48 patients without pelvic lymph node metastasis (group II) who were proven by pathologic examination of surgical specimens. HPV-16 or -18 DNAs were detectable in cervical carcinoma tissues in 60 patients from 79 cervical cancer patients (75.9%; HPV-16 was 67.1% and HPV-18 was 8.9%). HPV DNAs were amplified from metastatic pelvic lymph nodes in 13 patients of group I (42%) and from nonmetastatic lymph nodes in 7 group I patients (22.5%). Recurrence was identified in 9 group I patients (29.0%) in 3 years of follow-up. HPV DNAs were amplified from nonmetastatic lymph nodes in 11 group II patients (22.9%). Two group II patients, who had HPV-16 DNA by PCR in nonmetastatic nodes, were recurrent. PCNA was overexpressed in 66.7% of HPV-16- or -18-positive cervical cancers and 16.7% of HPV-16- or -18-negative cervical cancers. However, the expression levels of PCNA in cervical cancers were not influenced by the presence of oncogenic HPV DNA or pathologic metastasis in the pelvic lymph nodes. In conclusion, HPV DNA could be amplified from some metastatic and nonmetastatic pelvic lymph nodes and the detectability of oncogenic HPV DNA in pelvic lymph nodes may represent the poor outcome in the treatment of disease. The expression of PCNA protein which was associated with presence of oncogenic HPV DNAs in cervical cancers, suggesting activation of S phase of cell cycle, may contribute to the malignant progression by HPV-16 or -18.     

Low incidence of HPV DNA in sera of pretreatment cervical cancer patients

OBJECTIVE: The aim of this study was to investigate the feasibility of using DNA in the circulation as a diagnostic tool for cervical cancer. METHODS: We used PCR followed by Southern hybridization to detect human papillomavirus (HPV) DNA in serum samples taken from patients of cervical cancer before treatment. RESULTS: A total of 60 samples were analyzed. In a set of 40 samples, without knowledge of the HPV DNA status in the corresponding cervical carcinomas, we could detect 8 (20%) positive samples, of which 7 (17.5%) were HPV 16 and 1 (2.5%) was HPV 18. In another set of 20 samples, known to be HPV 16 infected in the corresponding cervical carcinomas, we detected only 4 (20%) HPV-16-positive samples. The occurrence of HPV DNA in sera of cervical cancer patients seems sporadic. CONCLUSION: The low incidence indicates that serum HPV DNA has limited application in the diagnosis of cervical cancer.     

Prevalence of genital human papillomavirus infection and genotypes among women from Fujian province, PR China

Objective

The prevalence and distribution of oncogenic human papillomavirus (HPV) genotypes in women who underwent screening for cervical cancer in Fujian province, China, were assessed and the correlation of genotypes with the histological results was evaluated.

Study design

Cervical samples were collected from 2338 women for cervical cancer screening. Participants were screened by liquid-based cytology and HPV genotyping using DNA Chip and referred to colposcopy and biopsy samples for further analyses if cytology results indicated undetermined significance (ASCUS) or higher.

Results

The prevalent types with cervical intraepithelial neoplasia 1 (CIN 1) were HPV-52 (22.5%), HPV-16 (11.6%) and HPV-CP8304 (10.1%). The prevalent types with cervical intraepithelial neoplasia 2 or 3 (CIN2/3) were HPV-16 (24.5%), HPV-33 (21.6%), and HPV-52 (19.6%). The prevalent types with carcinoma, including squamous cell carcinoma (SCC) and adenocarcinoma (ADCA), were HPV-16 (42.7%), HPV-18 (20.8%) and HPV-33 (12.5%). Analysis by odds ratio (OR) revealed that HPV-66, -68, and -CP8304 (HPV-CP8304: OR, 7.34; 95% confidence interval (CI) = 3.73-14.46) were associated with CIN 1; HPV-52 was CIN 2/3-associated type (OR, 7.25; 95%CI = 4.19-12.53); HPV-16, -18, -31, -33, -45, -53, -58, and -59 were associated with carcinoma (HPV-45: OR, 54.78; 95%CI = 10.49-286.16).

Conclusion

It was concluded that HPV infection in Chinese women in Fujian province showed higher frequencies of HPV-52 and HPV-33. However, HPV-16 was still the most common type in CIN2/3 and carcinoma. HPV-16, -18, -31, -33, -45, -53, -58 and -59 have more dominant oncogenic risk over other types in this area.     

Characterization of human papillomavirus genotypes and HPV-16 physical status in cervical neoplasias of women from northern Portugal

Objective

To determine human papillomavirus (HPV) genotypes and the physical status of HPV-16 DNA among women from northern Portugal with cervical lesions.

Methods

The present retrospective study included samples of cervical exfoliated cells from 88 women (median age 42.0 ± 13.1 years) who attended the Gynecology Service at the Portuguese Institute of Oncology in Porto during 2010. After DNA extraction, HPV genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism analysis using the MY09/MY11 primers. The physical status of HPV-16 was determined by real-time PCR.

Results

Overall, 69.3% of the samples tested positive. The prevalence of HPV infection was 38.5% in normal samples, 57.7% in cervicitis samples, and 87.2% in all cervical lesions including invasive cancers. Sixteen genotypes were detected, the most prevalent ones being HPV-16 (42.9%), HPV-31 (12.2%), and HPV-58 (10.2%); HPV-18 was rare. The overall prevalence of HPV-16 integration was 31.6%. The physical status of HPV-16 did not differ significantly by histology.

Conclusion

The most frequent genotypes were HPV-16, -31, and -58. Integration of HPV-16 DNA seemed to be an early event in cervical carcinogenesis. Further studies are required to clarify the value of viral integration as a prognostic marker.