Human Papillomavirus Polymerase Chain Research Articles

The yield of pap smears and its characteristics in a community based setting in Saudi Arabia.

Objectives:To assess the yield of Papanicolaou tests (pap smears), including the characteristics of abnormal pap smears.Methods:In this record-based cross-sectional study, we reviewed pap smears of patients seen at the Family Medicine clinics, King Faisal Specialist Hospital and Research Center from January 2002 to January 2017. All women between the ages of 21 and 65 were included. Study-specific case report form was developed to capture patient demographics, pap smear histopathology (Bethesda III System), human papilloma virus polymerase chain reaction (HPV PCR), and the parity status.Results:A total of 3346 patients were included; 2.2% had abnormal pap smear. Most frequent abnormalities were atypical squamous cells of undetermined significance (2%), followed by glandular cell abnormalities (0.8%). Human papilloma virus infection was detected in 6.5% and all other infections were identified in 9.2% of all screened Pap smears.Conclusion:Pap smears remain an effective tool for cervical cancer screening. Low yields of pap smears compared to other developed countries could be attributed to lower risk factors for cervical cancer in Saudi Arabia. Routine screening especially among high risk women is strongly recommended.

Assessing Urine Human Papillomavirus Polymerase Chain Reaction Testing As a Tool for Screening Anal HPV Infection in HIV-Positive MSM

Multiple types of human papillomavirus (HPV) are responsible for most cervical cancers but also cause anal cancers-especially in HIV-positive patients. Furthermore, men who have sex with men (MSM) are twice as likely to develop anal cancers as non-MSM. A simple screening test for HPV infection would be useful in these patients. The aim of our study was to evaluate the detection of HPV by real-time polymerase chain reaction (PCR) in urine as a marker of anal infection in MSM. The study included 52 HIV-positive MSM treated at Amiens University Hospital (Amiens, France). After obtaining informed consent, we performed an anal swab and gathered 10 mL of first-void urine. Samples were extracted and amplified in a real-time PCR. Genotypes were determined with a PapilloCheck(®) system (Greiner Bio-One, Frickenhausen, Germany). The anal test was the gold standard for calculating the characteristics of the urine test. The sensitivity of the urine test for diagnosing anal HPV infection was 15%, the specificity was 66%, the positive predictive value was 87.5%, and negative predictive value was 4.5%. The prevalence of anal HPV infection in the study population was 94%. Genotype 42 was the most common. The anal HPV viral load was significantly lower in men in a stable relationship than in single men. However, there was no statistically significant relationship between anal viral load and anal intraepithelial lesions. We conclude that urine-based HPV is a poor predictor of anal HPV infection in HIV-positive MSM.

Testing for methylated PCDH10 or WT1 is superior to the HPV test in detecting severe neoplasms (CIN3 or greater) in the triage of ASC-US smear results

Management of equivocal Papanicolaou smear result remains to be challenging even with the aid of human papillomavirus test. Recently, 3 novel methylation-silenced genes, PAX1, WT1, and PCDH10, have been found to be specifically associated with cervical cancer. We compared the performances of methylation test of these genes with human papillomavirus tests in triage of equivocal Papanicolaou smear result. Two hundred twenty-two women with Papanicolaou smear results of atypical cells of undetermined significance nested to a multicenter, nation-wide cohort (the T1899 cohort) were studied. Status of cervical neoplasm was diagnosed with colposcopic biopsy. Status of gene methylation was determined by methylation-specific polymerase chain reaction. High-risk human papillomavirus DNA was detected by polymerase chain reaction-reverse line blot hybridization and Hybrid Capture 2. Cervical intraepithelial neoplasm 1, cervical intraepithelial neoplasm 2, cervical intraepithelial neoplasm 3, carcinoma in situ, carcinoma, and normal cervix were diagnosed in 58, 17, 14, 10, 1, and 120 women, respectively. Methylation of PCDH10, WT1, and PAX1 was highly associated with the severity of cervical neoplasm (P < 10⁻⁹, < 10⁻⁷, and < 10⁻⁵, respectively). In comparison with a negative test result, the odds ratio (95% confidence intervals) for cervical intraepithelial neoplasm 3 or more severe neoplasms for women tested positive for methylation of these 3 genes were 26.4 (9.0-77.3), 18.1 (6.9-47.2), and 10.3 (4.1-25.9), respectively; whereas those positive for human papillomavirus polymerase chain reaction and Hybrid Capture 2 were 10.5 (3.5-31.9) and 5.6 (2.3-21.4). In triage for atypical cells of undetermined significance, each methylation test had less colposcopy referral and false-positive rates, but higher false-negative rate than the human papillomavirus tests. With a combination test of PCDH10 or WT1 methylation, a comparable false-negative rate (P = .62) but much less false-positive rate (P = .002) and colposcopy referral rate (P < 10⁻⁶) were achieved. In triage of atypical cells of undetermined significance Papanicolaou smear results, methylation test of WT1 and PCDH10 is superior to human papillomavirus test in this multicenter cohort. Comparing to current human papillomavirus triage, the new test has only one third of false positivity and half of colposcopy referral, with no compromise of the sensitivity in diagnosis of cervical intraepithelial neoplasm 3 or more severe neoplasms.

Epidemiologic analysis of histologic cervical inflammation: relationship to human papillomavirus infections

Infections with carcinogenic human papillomaviruses, the causal agents of cervical intraepithelial neoplasia and cancer, as well as infections with noncarcinogenic human papillomaviruses, are common but typically resolve spontaneously. Effective cell-mediated immune responses are critical for human papillomavirus clearance; however, data relating cervical inflammation to the outcome of human papillomavirus infection are lacking. To investigate this topic, we performed a masked parallel review of inflammation in the stroma and epithelium of cervical biopsies (n = 564) collected from a retrospectively defined subcohort of women systematically followed up in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study. Women in our analysis had undergone colposcopically directed enrollment biopsies diagnosed as negative or cervical intraepithelial neoplasia 1 and had corresponding human papillomavirus polymerase chain reaction test results of negative (n = 250), positive for a single carcinogenic (n = 237), or noncarcinogenic (n = 81) type. Inflammation in cervical stroma varied with cofactors for human papillomavirus progression: current smokers showed less inflammation (odds ratio, 0.55; 95% confidence interval, 0.31-0.97), whereas current oral contraceptive users had increased inflammation (odds ratio, 1.7; 95% confidence interval, 0.92-3.0) as did those with a self-reported 2-year history of a sexually transmitted disease (odds ratio, 1.9; 95% confidence interval, 1.0-3.5). Biopsies of women with carcinogenic human papillomaviruses had greater inflammation within the epithelium (odds ratio, 1.6; 95% confidence interval, 1.1-2.3) compared with human papillomavirus-negative women. Associations with human papillomavirus type-specific persistence or progression to histologic cervical intraepithelial neoplasia 3 were diminished among women with moderate or marked inflammation in stroma (odds ratio, 0.49; 95% confidence interval, 0.25-0.99) or within epithelium (odds ratio, 0.51; 95% confidence interval, 0.26-0.97). These data suggest that cervical inflammation varies with human papillomavirus cofactors, type of human papillomavirus infection, and risk of persistence and progression. Additional studies are needed to confirm and extend these findings.

No Metastatic Cervical Adenocarcinomas in a Series of p16INK4a-Positive Mucinous or Endometrioid Advanced Ovarian Carcinomas

Epithelial ovarian cancers may represent secondary manifestations of occult extraovarian carcinomas. Such tumors may be misdiagnosed as primary ovarian carcinomas clinically and pathologically. In a recent study, several cases of cervical cancer metastases with primary manifestation as mucinous or endometrioid ovarian carcinomas were described. In all cases, human papillomavirus (HPV) DNA and diffuse p16 immunostaining were detected in the ovarian tumor tissues. To estimate the frequency of occult metastatic endocervical adenocarcinomas in a series of mucinous or endometrioid ovarian carcinomas, 24 ovarian cancers with mucinous and 50 with endometrioid differentiation from the Arbeitsgemeinschaft Gynaekologische Onkologie OVAR-3 database were analyzed for HPV and p16 positivity. The p16 immunostaining was performed using the p16 histology kit (Dako, Glostrup, Denmark), and both nuclear and cytoplasmic staining results were considered positive. Human papillomavirus polymerase chain reaction analysis was performed using 2 consensus primer systems (GP5/GP6 and PGMY09/11) and HPV-16- and HPV-18-specific primers from the L1 and the E6 regions. Six (8%) of 74 tumors were p16-negative, 13 (18%) of 74 showed single positive cells, 28 (38%) of 74 showed focal homogeneous staining, and 27 (36%) of 74 showed complete diffuse staining. In several independent amplifications of different regions of the HPV genome, none of the 73 tumors available for analysis showed the presence of HPV DNA. No ovarian metastases of endocervical adenocarcinomas were found among mucinous and endometrioid adenocarcinomas from a large chemotherapy trial of advanced stage ovarian carcinomas. The p16 staining detected in many primary ovarian adenocarcinomas in the present series seems independent from HPV oncogene activity.

Papillary Eccrine Adenoma in Association with Cutaneous Horn

Papillary eccrine adenoma (PEA) is an uncommon sweat gland neoplasm that occurs more frequently on the distal extremities of Black women. Clinically, it appears as a small, isolated, firm, dome-shaped cutaneous nodule. We report two unusual cases of PEA that presented clinically as cutaneous horn. Histologically, both cases showed the typical dermal morphology of PEA with overlying epidermal changes suggestive of human papillomavirus (HPV). However, HPV immunoperoxidase staining and polymerase chain reaction for HPV were negative in both cases. Concurrent occurrence of PEA and HPV-like epidermal changes may be coincidental; however, their co-occurrence may also be related to the environment induced by this adnexal tumor. Whether PEA with verrucous epidermal changes has a different clinical behavior or increased risk for a malignant transformation is unknown, as both patients were lost to follow-up.