Jackie Jamison

p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection.

Houghton O, Jamison J, Wilson R, Carson J & McCluggage W G
(2010) Histopathology 57, 342–350
p16 Immunoreactivity in unusual types of cervical adenocarcinoma does not reflect human papillomavirus infection

Type-specific HPV prevalence in invasive cervical cancer in the UK prior to national HPV immunisation programme: baseline for monitoring the effects of immunisation

Aims To establish the human papillomavirus (HPV) type-specific prevalence in cervical cancer and high-grade cervical lesions in the UK prior to the introduction of national HPV vaccination. Methods Specimens of cervical cancer (n=1235) and cervical intraepithelial neoplasia (CIN)3 (n=2268) were tested for HPV genotypes in England, Scotland, Wales and Northern Ireland. Data were pooled and weighted estimates presented. Results Among cervical cancer cases, 95.8% were positive for at least one high-risk (HR) HPV type. Restricting to those with HR HPV, the proportion positive for HPV16 and/or HPV18 was similar across countries (weighted overall prevalence 83.0%). This proportion decreased with increasing age at diagnosis (p=0.0005). HPV31, HPV33, HPV45, HPV52 and/or HPV58 were detected in 16.1% of HR HPV-positive cervical cancers and there was no significant association with age for these types. For HR HPV-positive CIN3 cases, there was a similar age-specific pattern with the highest positivity of HPV16 and/or HPV18 in the youngest age group (77.2%). The proportion of HR HPV CIN3 cases positive for HPV31, HPV33, HPV45, HPV52 and/or HPV58 was 36.3% in those aged <30 years at diagnosis. Conclusions The prevalence of HPV 16 and/or 18 was high in all UK countries and highest in those diagnosed at a younger age. The UK is well placed to monitor the impact of HPV vaccination on type-specific HPV prevalence in cervical disease.

Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland: New data from northern Ireland and a systematic review and meta-analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta‐analysis pooling the prevalence of high‐risk (HR‐HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta‐analysis was used to calculate a pooled HR‐HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20–64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high‐grade cytological findings, respectively. Crude HR‐HPV prevalence was 13.2% (95% CI, 12.7–13.7) among women with normal cytology and increased with cytological grade. In meta‐analysis the pooled HR‐HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10–0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02–0.05) and 0.01 (95% CI, 0.01–0.02), respectively. The findings of this Northern Ireland study and meta‐analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type‐specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR‐HPV types other than HPV 16 and 18. J. Med. Virol. 85:295–308, 2013.

The evaluation of human papillomavirus genotyping in cervical liquid-based cytology specimens; using the Roche Linear Array HPV genotyping assay.

Objective:  To ascertain the usefulness of the Roche Linear Array human papillomavirus (HPV) genotyping assay for assessing HPV genotypes in liquid‐based cytology (LBC) samples and to evaluate this methodology within a cytopathology laboratory. These tests are of importance as persistent infection with high‐risk HPV genotypes is considered a causal factor in the development of cervical cancer.

The prevalence of viral agents in esophageal adenocarcinoma and Barrett’s esophagus: A systematic review

Background and aims Human papilloma virus (HPV), which may reach the esophagus through orogenital transmission, has been postulated to be associated with esophageal adenocarcinoma (EAC). A systematic review of the literature investigating the prevalence of infectious agents in EAC and Barrett’s esophagus (BE) was carried out. Methods Using terms for viruses and EAC, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until June 2016 that assessed the prevalence of viral agents in EAC or BE. Random-effects meta-analyses of proportions were carried out to calculate the pooled prevalence and 95% confidence intervals (CIs) of infections in EAC and BE. Results A total of 30 studies were included. The pooled prevalence of HPV in EAC tumor samples was 13% (n=19 studies, 95% CI: 2–29%) and 26% (n=6 studies, 95% CI: 3–59%) in BE samples. HPV prevalence was higher in EAC tissue than in esophageal tissue from healthy controls (n=5 studies, pooled odds ratio=3.31, 95% CI: 1.15–9.50). The prevalence of Epstein–Barr virus (EBV) in EAC was 6% (n=5, 95% CI: 0–27%). Few studies have assessed other infectious agents. For each of the analyses, considerable between-study variation was observed (I2=84–96%); however, sensitivity analyses did not show any major sources of heterogeneity. Conclusion The prevalence of HPV and EBV in EAC is low compared with other viral-associated cancers, but may have been hampered by small sample sizes and detection methods susceptible to fixation processes. Additional research with adequate sample sizes and high-quality detection methods is required.

HPV prevalence and type-distribution in cervical cancer and premalignant lesions of the cervix: A population-based study from Northern Ireland

Assessment of Human papillomavirus (HPV) prevalence and genotype distribution is important for monitoring the impact of prophylactic HPV vaccination. This study aimed to demonstrate the HPV genotypes predominating in pre‐malignant and cervical cancers in Northern Ireland (NI) before the vaccination campaign has effect. Formalin fixed paraffin embedded tissue blocks from 2,303 women aged 16–93 years throughout NI were collated between April 2011 and February 2013. HPV DNA was amplified by PCR and HPV genotyping undertaken using the Roche® linear array detection kit. In total, 1,241 out of 1,830 eligible samples (68.0%) tested positive for HPV, with the majority of these [1,181/1,830 (64.5%)] having high‐risk (HR) HPV infection; 37.4% were positive for HPV‐16 (n = 684) and 5.1% for HPV‐18 (n = 93). HPV type‐specific prevalence was 48.1%, 65.9%, 81.3%, 92.2%, and 64.3% among cervical intraepithelial neoplasias (CIN) Grades I–III, squamous cell carcinomas (SCC) and adenocarcinoma (AC) cases, respectively. Most SCC cases (81.3%) had only one HPV genotype detected and almost a third (32.0%) of all cervical pathologies were HPV negative including 51.9% of CIN I (n = 283), 34.1% CIN II (n = 145), 18.7% of CIN III (n = 146), 7.8% of SCC (n = 5), and 35.7% of AC (n = 5) cases. This study provides important baseline data for monitoring the effect of HPV vaccination in NI and for comparison with other UK regions. The coverage of other HR‐HPV genotypes apart from 16 and 18, including HPV‐45, 31, 39, and 52, and the potential for cross protection, should be considered when considering future polyvalent vaccines. J. Med. Virol. 88:1262–1270, 2016.

Inverted papilloma of the cervix and vagina: report of 2 cases of a rare lesion associated with human papillomavirus 42

We report 2 cases of a lesion that we term inverted papilloma of the lower female genital tract, occurring in the cervix and upper vagina of 60- and 50-year-old women, respectively. Microscopically, the features were similar to those of inverted transitional papilloma of the urinary bladder with interconnecting islands, trabeculae, and solid sheets of bland transitional epithelium with an inverted growth pattern. There were small foci of squamous and glandular differentiation in the cervical case. Linear array human papillomavirus genotyping revealed human papillomavirus type 42 in both cases. Inverted papilloma in the lower female genital tract is extremely rare with, as far as we are aware, only 3 previously reported similar cases in the cervix and none in the vagina. Our results suggest that these neoplasms when occurring in the lower female genital tract may be associated with low-risk human papillomavirus, perhaps specifically human papillomavirus 42.

Cervical Squamous Carcinomas With Prominent Acantholysis and Areas Resembling Breast Lobular Carcinoma: An Aggressive Form of Dedifferentation

There have been occasional reports of primary cervical adenocarcinoma with areas of dedifferentiation resulting in morphologic mimicry of breast lobular carcinoma. We describe 4 cases of primary cervical squamous carcinoma with prominent acantholysis (3 cases), areas resembling breast lobular carcinoma (3 cases) or both (2 cases). All 4 tumors showed positivity with p63 and CK5/6 and 3 of 4 exhibited block-type immunoreactivity with p16. Two of the 4 cases contained high-risk human papillomavirus (types 16 and 18) on molecular testing; of the 2 cases which were human papillomavirus negative, 1 exhibited patchy nonblock immunoreactivity with p16. All cases exhibited some degree of loss of E-cadherin membranous staining in the areas of acantholysis and foci resembling breast lobular carcinoma. Three of 4 patients had extracervical spread at diagnosis; the fourth patient developed extracervical recurrence on follow-up. The initial FIGO stages were IB1, IIB (2 cases) and IVB. The 2 patients whose neoplasms were human papillomavirus negative developed distant metastases (supraclavicular, meningeal, and lung) during the course of their disease; the same 2 patients died of disease at periods of 4 mo and 1 yr after diagnosis. Cervical squamous carcinomas with acantholytic features and areas resembling breast lobular carcinoma are an unusual morphologic variant of squamous carcinoma. We consider the acantholysis and mimicry of breast lobular carcinoma to be part of a spectrum of morphologic changes, possibly related to loss of E-cadherin. These features can be regarded as a form of dedifferentiation which indicates a potential for aggressive behavior.