HPV genotype prevalence in women with abnormal pap smears in Melbourne,Australia

Carcinoma of the cervix and its precursor, high‐grade cervical intraepithelial neoplasia (CIN2/3), are associated with persistent oncogenic Human papillomavirus (HPV) infection, particularly HPV 16 and 18. HPV genotype distribution varies with severity of cervical disease, patient demographics such as age, as well as geographical location. In this study, HPV genotype prevalence was determined, using the Roche Linear Array genotyping test, among a cohort of 1,676 women being managed with ablative or excisional treatment following colposcopically directed biopsies, who were referred initially due to cytological abnormalities. HPV genotype prevalence, including presence of single and multiple infections was assessed against both histological diagnosis and age. Overall, 83.9% of women were identified as HPV positive, comprising of 32.2% single and 51.7% multiple HPV infections. Of those with an available histological diagnosis at time‐of‐treatment (n = 899), HPV positivity increased significantly with disease severity: 62.4% (normal), 77.6% (CIN1), 92.6% (CIN2), and 97.9% (≥CIN3) (P < 0.006). Similarly, a significant increase in high‐risk (HR) HPV detection was observed with severity of disease (P < 0.005). The five most prevalent genotypes were HPV 16 (35.1%), 31 (12.6%), 51 (11.1%), 52 (9.9%), and 18 (8.5%). HPV 16 was the only genotype to demonstrate a significant increase in prevalence with increasing severity of histological or cytological disease (P < 0.0001). Multiple HPV infections, including multiple HR‐HPV infections, declined significantly with age (P < 0.02). These findings provide the largest dataset of HPV genotype prevalence rates within Australian women, though are not representative of the general population. J. Med. Virol. 81:1283–1291, 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of the clinical significance of the Papanicolaou test interpretations LSIL cannot rule out HSIL and ASC‐H

Despite the two‐tiered classification of dysplasia in The Bethesda System (TBS), rare cases fall into the category squamous intraepithelial lesion (SIL) of indeterminate grade. These Pap tests are often interpreted as “LSIL/ASC‐H” or “LSIL” with a comment indicating the presence of cells with features approaching HSIL. Patients with LSIL/ASC‐H have a significant risk of CIN 2 or worse (29–61.5%) on follow‐up cervical biopsies, similar to the risk of CIN 2 or worse in patients with ASC‐H Pap tests (24–68%). The purpose of this study was to compare patients with ASC‐H and LSIL/ASC‐H Pap tests. Women with LSIL/ASC‐H had a slightly lower incidence of CIN 2 or worse (PPV = 35.6%, 95% CI: 29.8–41.4%) on follow‐up cervical biopsy than the control ASC‐H group (PPV = 40.2%, 95% CI: 31.9–56.3%); this difference was not statistically significant. The difference in the distribution of the biopsy results between the two groups was statistically significant (P < 0.001). The current guidelines for the management of cervical cytologic abnormalities from the American Society for Colposcopy and Cervical Pathology (ASCCP) advocate similar treatment algorithms for both LSIL and ASC‐H. The main difference is the option of cytologic follow‐up or HPV testing for certain “special populations,” as an alternative to colposcopy, for LSIL Pap test results. Based on our results, we recommend (1)LSIL/ASC‐H to be added to TBS classification and (2) Pap test cases of LSIL/ASC‐H may need to be clinically followed in a manner similar to ASC‐H, i.e., colposcopy for all patients. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

HPV testing in patients with low grade cervical cytological abnormalities: a follow up study.

AIM: To assess the diagnostic performance of human papillomavirus (HPV) analysis in predicting cervical intraepithelial neoplasia (CIN) grades 2 and 3 in patients with persistent low grade cervical cytological abnormalities. METHODS: Cervical smears from 167 women referred for colposcopy with persistent borderline, wart virus or mildly dyskaryotic changes on cervical screening were analysed by Papanicolaou staining, non-isotopic in situ hybridisation and generic and type specific polymerase chain reaction (PCR) amplification of HPV sequences. Follow up was by cytological and, where appropriate, histological analysis. RESULTS: CIN grade 2 or 3 was identified in 46 patients after a median follow up of 27 months. HPV positivity by both techniques was associated with high grade CIN and with age less than 30 years (median age 33 years). Non-isotopic in situ hybridisation was more predictive but less sensitive than either generic or type specific PCR, but prediction was greater using either molecular technique in women over 30 years of age. CONCLUSIONS: Although the degree of prediction found is of only limited clinical value, the strong association of HPV positivity with both high grade CIN and patient age suggests that further studies of HPV testing in this patient group are warranted.     

Assessment of the effectiveness of HPV16/18 infection referred for colposcopy in cervical cancer screening in Northwest of China

To evaluate the effectiveness of Human papillomavirus16/18 infection referral to colposcopy in cervical cancer screening for women aged 25 years and older in Chinese northwest region Shaan'xi province. A total of 2224 women were diagnosed with primary high‐risk HPV infection by HPV‐DNA genotyping technology during August 2014 to August 2015. A total of 1916 cases referred for colposcopy with histological evidence were enrolled, including 1124 women with HPV16/18 genotype and 792 with other High‐risk human papillomavirus genotypes. A total of 1916 women aged 25 years and older with HR‐HPV positive were referred to colposcopy. The distribution of HPV16, HPV18, and other HR‐HPVs infection were 49.22%, 9.45%, and 41.33%, respectively. 71.56% had normal cervical histology, 7.05% had Cervical Intraepithelial Neoplasia1, 8.82% had CIN2, 7.25% had CIN3, and 5.32% had cervical cancer. The percentage of positivity of HPV16 and HPV18 was highly associated with the relative risk of cervical lesion. The sensitivity and specificity of HPV16/18 for detection of CIN2+ (CIN3+) was 82.68% (92.12%) and 47.87% (46.15%), respectively. The positive predictive value and negative predictive value of HPV16/18 for detection of CIN2+ (CIN3+) was 30.16% (19.75%) and 91.03% (97.60%), respectively. HPV16 and HVP18 are the most common genotypes in high grade cervical lesions in Shaan'xi province. Meanwhile, these two types play predominant roles in the progression of high grade cervical lesion. Primary HPV16/18 detection has high sensitivity and negative predictive value in cervical cancer screening and the strategy for women with HPV16 and HPV18 infection referral to colposcopy is efficient and feasible in northwestern region of China.     

Cervical infections by multiple human papillomavirus (HPV) genotypes: Prevalence and impact on the risk of precancerous epithelial lesions

A large proportion of human papillomavirus (HPV) infections is sustained by multiple genotypes. The effect of multiple infections on the risk of cervical intraepithelial neoplasia (CIN) and the potential efficacy of vaccine on these infections are controversial. We performed viral typing by SFP₁₀‐LIPA on a consecutive series of 1,323 women undergoing colposcopy, 69% of whom had cervical biopsy, and correlated CIN severity with the type and number of HPVs. Overall prevalence of HPV‐DNA was 68.9%, 97.3% in CIN1, and 98.1% in CIN≥2. HPV positivity correlated with younger age (35.9 vs. 37.3 years, P = 0.026) and history of CIN (P < 0.001). Multiple types were detected in 44.2% of cases, including 63.1% CIN1 and 80.8% CIN≥2. Twenty‐three different types were detected, HPV‐16, 31 and 52 being the most frequent. Infections by HPV‐6, 11, 16, or 18 occurred in 59.4% of CIN1 and 71.3% of CIN≥2. Number of viral types and class of oncogenic risk were linearly correlated with CIN severity (P < 0.0001) by univariate and multivariate analyses controlling for age and history of CIN. The effect of the number of HPV types was maintained after exclusion from the model of infections by HPV‐6, 11, 16, and 18. Frequency, distribution, and clinical correlates of multiple HPV infections highlight the importance of assessing individual types in the management and the prediction of outcome of women with abnormal baseline cytology and point to potential limitations in current vaccine strategies. J. Med. Virol. 81:703–712, 2009 © 2009 Wiley‐Liss, Inc.     

Prevalence characteristics of single and multiple HPV infections in women with cervical cancer and precancerous lesions in Beijing,China

We assessed the prevalence characteristics of single and multiple high-risk human papillomavirus (HR-HPV) infections. A total of 1783 women who underwent colposcopy and cervical biopsy for abnormal ThinPrep Cytology Test and/or HR-HPV subtype genotyping results were enrolled in the study. Among the participants, 770 were diagnosed with cervicitis, 395 with cervical intraepithelial neoplasia grade 1 (CIN1), 542 with CIN2-3, and 76 with squamous cell carcinoma (SCC), with HR-HPV infection rates of 75.8%, 85.8%, 95.9%, and 88.4%, respectively. The prevalence of total and multiple HR-HPV infections exhibited a bimodal age distribution with a peak at ≤25 years, a decline with age and a second peak at ≥55 years, whereas single HR-HPV infections exhibited one peak from 35 to 44 years. The four most dominant HPV genotypes were HPV 16 (29.5%), 52 (15.0%), 58 (14.2%), and 18 (10.4%). In total, 67.0%, 70.4%, and 82.1% of patients with CIN1, CIN2-3, and SCC, respectively, had a single HR-HPV infection, which increased significantly with the aggravation of the cervical lesion grade (P = 0.045). Patients with a single HPV 16 infection had higher incidences of CIN2+ (62.2%) than those with multiple HPV 16 infections (52.4%) (P = 0.021). Patients coinfected with HPV 16 had higher CIN2+ incidence than those with single HPV 52, 31, 33, 35, 39, 45, 51, 56, or 59 infections (P < 0.001). This study provided baseline data on the prevalence characteristics of single and multiple HR-HPV infections in women attending a gynecological outpatient clinic in Beijing.     

宫颈上皮内瘤变及其治疗对妊娠的影响

宫颈鳞状上皮内瘤变是一种和HPV感染有关的宫颈癌前病变。根据病变程度分为低度和高度鳞状上皮内病变,其中低度病变包括HPV感染和C IN1,高度病变包括C IN2~3。HPV感染和宫颈上皮内瘤变是一种生育年龄妇女常见的妇科疾病,HPV感染、宫颈病变本身及其治疗对妊娠的影响倍受关注。HPV感染在妊娠期间可能增加,经阴道分娩者新生儿暴露于HPV的机会增多,尚不能下结论对所有HPV感染者均采用剖宫产的分娩方式。妊娠期间发现C IN1,可以观察并产后随访。如果为C IN2~3,妊娠可能不会加重病变程度,但对阴道镜检查不满意者或高度怀疑浸润癌者应在孕期明确诊断,可于妊娠中期行宫颈锥切术。妊娠中期行宫颈锥切术可能使剖宫产率增加。C IN保守治疗对于患者受孕能力无显著的影响;宫颈冷刀锥切及LEEP锥切可能增加早产率,早产率的增加可能和胎膜早破的发生有关。     

Epidemiology and persistence of cervical human papillomavirus infection among outpatient women in Heilongjiang province: A retrospective cohort study

As persistent carcinogenic human papillomavirus (HPV) infection is a prominent driver of cervical cancer, it is essential to explore HPV persistence and its associated factors for cancer screening and prevention. A retrospective cohort study was performed in outpatient women between March 2010 and 2019 in Heilongjiang, northeast China. HPV genotyping was performed by polymerase chain reaction-membrane hybridization. An unconditional logistic regression model was used to analyze the association of factors with persistence. The overall prevalence of HPV at baseline was 27.1%, with a downward trend from 2010 to 2019 (P < .0001). The most commonly observed high- and low-risk HPVs were HPV16 (N = 1094, 5.9%) and HPV11 (N = 596, 3.2%), respectively. The probabilities of 6-month persistence were high for women infected with HPV16 (P = .0001), HPV58 (P = .018), and HPV53 (P = .014), as well as for women with multiple infections (P = .009), and those who were 51 to 60 years old (P = .004) or more than 60 years old (P = .007). The probabilities of 12-month persistence were high for women infected with HPV53 (P = .017) and 51- to 60-year-old women (P = .044). HPV16 is the dominant HPV type in Heilongjiang. An age in the range of 51 to 60 years and infection with HPV53 is associated with HPV infection persistence in the Heilongjiang population.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or cervical intraepithelial neoplasia in Henan province,central China

To evaluate the prevalence of human papillomavirus (HPV) infection and its genotype among women with cervical lesions in Henan Province, central China. A total of 1317 cervical scrapes from patients with cervical intraepithelial neoplasia 1 (CIN1) (n = 91), CIN2/3 (n = 466), and cervical cancer (CC; n = 760) were collected from 2013 to 2018, and then tested for HPV genotypes using polymerase chain reaction followed by flow-through hybridization assay. The prevalence of HPV was 62.64% for patients with CIN1, 86.91% for patients with CIN2/3%, and 89.21% for patients with CC. In total, the HPV prevalence was 86.56%, and the most common HPV type was HPV16 (58.77%) followed by HPV58 (10.33%), 18 (7.67%), 52 (6.61%), and 33 (5.54%). In this study, the high-risk HPV cumulative attribution rate of nine-valent vaccine coverage was markedly higher than that of bivalent or quadrivalent vaccine coverage in each histopathological category or overall (P < .001). Single HPV infection was the main infection category in each histopathological diagnosis, and the total infection rate was 65.83% (867/1317; P < .001). The prevalence of HPV16 or single HPV infection increased with the severity of cervical lesions (P < .001). HPV16, 58, 18, 52, and 33 may be predominant high-risk factors for cervical lesions in Henan Province. The nine-valent prophylactic HPV vaccine is more effective than a bivalent or quadrivalent vaccine for protecting women from CC in the region.     

P16 and Ki-67 expression improves the diagnostic accuracy of cervical lesions but not predict persistent high risk human papillomavirus infection with CIN1

Objective: To determine the association between the expression of p16 and Ki-67 and cervical lesions, and to evaluate the role of p16 and Ki-67 as prognostic markers for persistent high risk human papillomavirus (hr-HPV) infection. Methods: Totally 1,154 cases of cervical biopsies were enrolled, 331 cases with negative for dysplasia (NEG), 462 with cervical intraepithelial neoplasia 1 (CIN1), 176 with CIN2, 163 with CIN3 and 22 with cervical squamous cell carcinoma (SCC). Furthermore, 283 women with CIN1 were recruited into 12-month follow-up, and HPV specific gene detection by polymerase chain reaction was used to detect hr-HPV of cervical secretions at 6-month-interval for 12-month follow-up period. 40 women were infected with persistent hr-HPV, 182 with transient infection and 61 unfected with hr-HPV. The expression of p16 and Ki-67 were evaluated by immunohistochemical method. The immunostaining results of p16 and Ki-67 were classified into four categories: negative, 1+, 2+ and 3+. Results: There was significant increase in the expression of p16 (P < 0.001) and Ki-67 (P < 0.001) from NEG to SCC. The expression of Ki-67 (P < 0.001) but not p16 (P = 0.254) significantly increased in CIN2, CIN3. Ratio of p16 (P = 0.215) and Ki-67 (P = 0.495) positivity were not correlated with persistent hr-HPV infection. Conclusion: P16 and Ki-67 can improve the diagnostic accuracy of cervical lesions but can not predict persistent hr-HPV infection with CIN1.     

Enhancing the scope of conventional cervical cytology for detecting HPV infection

Cervical neoplasia is attributed to a persistent Human Papilloma Virus infection. The Pap smear being the mainstay of cervical cancer screening in low‐resource settings, we studied the nonclassical features which might indicate HPV infection. These included abortive koilocytes, mild dyskeratosis, parakeratosis, mild nuclear hyperchromasia, bi/multinucleation, measles cells, and keratohyaline‐like granules. Two hundred and eight women with a satisfactory Pap smear and a Hybrid Capture II test were compared against the “HPV Gold Standard” for validation of the nonclassical signs. This was defined as one with any/all of the following: definite HPV‐related lesions on Pap smear (LSIL and above), hrHPV positivity, and CIN I, or above on histology. The highest PPV and NPV were achieved by bi/multinucleation and mild nuclear hyperchromasia, respectively. The mean number of nonclassical signs for HPV Gold Standard‐positive and ‐negative groups was 5.52 and 3.12 per smear, respectively (P < 0.0005). Abortive koilocytes, mild dyskeratosis, mild nuclear hyperchromasia, bi/multinucleation, parakeratosis, and diffuse keratohyaline granules had the best correlation with the gold standard (P < 0.05). Addition of nonclassical signs to established intraepithelial lesions on Pap smear increased the sensitivity from 52.31to 59.10% and reduced the specificity from 100 to 98%. To maximize the benefit from grouping of these signs, various combinations were studied. The best was: abortive koilocytes, mild nuclear hyperchromasia, and bi/multinucleation. Another was abortive koilocytes, mild nuclear hyperchromasia, bi/multinucleation, and mild dyskeratosis. In conclusion, these signs proved useful for identifying HPV infection. Population‐based studies are required to corroborate our findings. Diagn. Cytopathol. 2010;38:645–651. © 2009 Wiley‐Liss, Inc.     

Moderate variation of the oncogenic potential among high-risk human papillomavirus types in gynecologic patients with cervical abnormalities

The oncogenic potential of human papillomavirus (HPV) infection was assessed by following the disease course in 455 patients who had had a routine diagnostic Hybrid Capture HPV test due to squamous cell abnormalities of the uterine cervix as detected by cytology and/or colposcopy. At entry, 308 patients had cytologic atypia classified as P3 by the Papanicolau classification, 168 had a positive high-risk HPV test, and 23 were infected only with low-risk HPV. The patients were followed-up using the patient registry until the endpoint of histologically diagnosed cervical intraepithelial neoplasia (CIN). High-grade CIN was diagnosed in 75 surgical biopsies. High-risk HPV infection (relative risk: 76.8 CI(95): 23.7-249.5), cytologic atypia (RR: 16.2 CI(95): 3.9-66.6), and age above 35 (RR: 1.99 CI(95): 1.26-3.16) were independent risk factors for high-grade CIN, while the viral load did not predict oncogenic progression (P = 0.47). After PCR-RFLP typing, the high-risk types were classified into groups as follows: (1) types 16 and 18, (2) types 45, 52, and 56, (3) types 31, 33, 35, 51, and 58. The relative risks of high-grade CIN were 119.1 (CI(95): 36.2-390.9) for group 1, 44.4 (CI(95): 9.8-201) for group 2, and 39.7 (CI(95): 10.9-144.8) for group 3, respectively. The risk ratios between the groups of high-risk types were found to differ at most by a factor of 2.98 (corrected P value: 0.007) indicating that the oncogenic potential varies moderately within the high-risk group of HPVs.     

Distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia and invasive cervical cancer in Canada

Infection with high‐risk human papillomavirus (HPV) causes cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC). The distribution of HPV types in cervical diseases has been previously described in small studies for Canadian women. The prevalence of 36 HPV genotypes in 873 women with CIN and 252 women with ICC was assessed on cervical exfoliated cells analyzed with the Linear Array (Roche Molecular System). HPV16 was the most common genotype in CIN and ICC. The seven most frequent genotypes in order of decreasing frequency were HPV16, 51, 52, 31, 39, 18, and 56 in women with CIN1, HPV16, 52, 31, 18, 51, 39, and 33 in women with CIN2, HPV16, 31, 18, 52, 39, 33, and 58 in women with CIN3, and HPV16, 18, 45, 33, 31, 39, and 53 in women with ICC. HPV18 was detected more frequently in adenocarcinoma than squamous cell carcinoma (P = 0.013). Adjustment for multiple type infections resulted in a lower percentage attribution in CIN of HPV types other than 16 or 18. The proportion of samples containing at least one oncogenic type was greater in CIN2 (98.4%) or CIN3 (100%) than in CIN1 (80.1%; P < 0.001 for each comparison). Multiple type infections were demonstrated in 51 (20.2%) of 252 ICC in contrast to 146 (61.3%) of 238 women with CIN3 (P < 0.001). Adjusting for multiple HPV types, HPV16 accounted for 52.1% and HPV18 for 18.1% of ICCs, for a total of 70.2%. Current HPV vaccines should protect against HPV types responsible for 70% of ICCs in Canadian women. J. Med. Virol. 83:1034–1041, 2011. © 2011 Wiley‐Liss, Inc.     

Post‐cervical conization outcomes in patients with high‐grade intraepithelial lesions

To investigate the rates of residual, recurrent and invasive disease after cervical conization in patients diagnosed with cervical intraepithelial neoplasia (CIN) grades 2/3. A retrospective study was conducted with 274 patients undergoing cervical conization due to diagnosis of CIN 2/3. Cervical conization was done through the Loop Electrosurgical Excision Procedure (LEEP) and Cold Knife Conization. Data related to personal, familial, gynecological, and obstetric antecedents, as well as surgical specimens margins were collected from medical records. The outcome after conization was evaluated, including the time of follow‐up and disease recurrence. The outcome after conization was not associated with age of menarche (p = 0.920), age of the first sexual intercourse (p = 0.533), number of parturition (p = 0.063), number of sexual partners (p = 0.328), immunosuppression (p = 0.225), smoking habit (p = 0.193), and conization type (p = 0.198). However, the outcome presented a significant association with age (p < 0.001), pregnancy numbers (p = 0.009), use of hormonal contraception methods (p = 0.016), menopause (p = 0.007), type of margins (p = 0.011), and cone histological results (p = 0.030). The routine control of all patients who had undergone cervical conization is obligate, independently of surgical margins, due to the risk of disease recurrence; the older patients and those with CIN 3 should have a more rigorous follow‐up.     

Human papillomavirus (HPV) DNA triage of women with atypical squamous cells of undetermined significance with Amplicor HPV and Hybrid Capture 2 assays for detection of high-grade lesions of the uterine cervix

Up to 20% of women having a cytology smear showing atypical squamous cells of undetermined significance (ASC-US) and infected with high-risk human papillomavirus (HR HPV) have high-grade cervical intraepithelial neoplasia (CIN 2/3). Results obtained with the Amplicor HPV and Hybrid Capture 2 (HC-2) assays for HR HPV DNA detection in women referred to colposcopy for an ASC-US smear were compared. Cervical samples in PreservCyt were tested for the presence of 13 HR HPV types with HC-2, with Amplicor at three cutoffs for positivity (0.2, 1.0, and 1.5 optical density units), and for 36 genotypes with the Linear Array (LA). Of 396 eligible women, 316 did not have CIN, 47 had CIN 1, 29 had CIN 2/3, and 4 had CIN of unknown grade. HR HPV was detected in 129 (32.6%) and 164 (41.4%) samples with HC-2 and Amplicor HPV (cutoff, 0.2), respectively (P = 0.01). Overall, 112 specimens were positive and 215 were negative with the HC-2 and Amplicor HPV assays (agreement of 82.6%; 95% confidence interval [CI], 78.5 to 86.0). The clinical sensitivity and specificity of Amplicor HPV at cutoffs of 0.2, 1.0 and 1.5 and of HC-2 for detection of CIN 2/3 were 89.7% (95% CI, 72.8 to 97.2) and 62.5% (95% CI, 57.5 to 52.4), 89.7% (95% CI, 72.8 to 97.2) and 64.5% (95% CI, 59.4 to 69.2), 89.7% (95% CI, 72.8 to 97.2) and 64.7% (95% CI, 59.7 to 69.5), and 93.1% (95% CI, 77.0 to 99.2) and 72.2% (95% CI, 67.4 to 76.5), respectively. Both HR HPV detection tests identified women with ASC-US who would benefit the most from colposcopy. Women with persistent HR HPV infection need further investigation despite a first normal colposcopy.     

The relationship between the cervical and anal HPV infection in women with cervical intraepithelial neoplasia

BackgroundMore than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor.ObjectivesTo demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer.Study designA total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test.ResultsCervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection.ConclusionsConcurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.     

High frequency of multiple HPV types in cervical specimens from Danish women

Genital human papillomavirus infection (HPV) is common and usually harmless. However, chronic cervical infection with high‐risk HPV types can cause cell changes that may eventually lead to cancer. To determine the frequency of individual HPV types among mixed infections, we examined the type distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using microarray technology, we found that 49% of the HPV‐positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high‐risk HPV type was HPV‐16, which was found in 25% of the HPV‐positive cervical specimens. Among the HPV positive CIN2+ diagnosed women, 48% were HPV‐16 positive. Women younger than 30 years of age had a higher frequency of multiple infections (61%) than women older than 30 years (39%). We conclude that cervical infection with multiple HPV types is common among women in all age groups and among women with or without the diagnosis of CIN2+.     

The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report

We examined the predictors (cytologic interpretations, pathology review, human papillomavirus [HPV] testing results, and colposcopic impressions) of precancer among 545 women with clinical center biopsy diagnoses of cervical intraepithelial neoplasia (CIN) 2 in the ASCUS LSIL Triage Study. Among women with a CIN 2 biopsy result, there was an increasing likelihood that the loop electrosurgical excision procedure (LEEP) tissue sample was diagnosed as precancer (CIN 3) with an increasing number of clinical risk factors of cervical precancer (high-grade squamous intraepithelial lesion [HSIL] cytology, high-grade colposcopy, detection of HPV type 16; Ptrend < .0005). In a multivariate model, using a case definition of worst histologic diagnosis made by the quality control pathology review of biopsy and LEEP tissue samples, HPV-16 was positively associated (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.6-8.8) with a CIN 3 diagnosis, whereas testing negative for HPV or positive for noncarcinogenic HPV types was negatively associated (OR, 0.32; 95% CI, 0.14-0.75) with a CIN 3 diagnosis. Although we found clear evidence that HPV-16 detection helped clarify whether a biopsy specimen diagnosed as CIN 2 represented HPV infection or cervical precancer, this relationship was not sufficiently robust to be clinically useful for reducing the overtreatment of women with HPV infection.     

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low‐grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low‐grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16‐specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16‐specific neutralizing antibodies (P = 0.03, log‐rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16‐specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low‐grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression. J. Med. Virol. 84: 1128–1134, 2012. © 2012 Wiley Periodicals, Inc.