Bjørn Enge Bertelsen

Landscape of genomic alterations in cervical carcinomas

Cervical cancer is responsible for 10–15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma–normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour–normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.

Expression of keratin 13, 14 and 19 in oral squamous cell carcinomas from Sudanese snuff dippers: Lack of association with human papillomavirus infection

In stratified squamous epithelia, altered expression of keratins (Ks) is one possible marker of malignant potential. In the epithelium of the uterine cervix, presence of human papillomaviruses (HPVs) is increasingly regarded as a marker of risk for cervical cancer. However, a similar role in oral cancer and precancer remains controversial. To address these questions, formalin‐fixed, paraffin‐embedded oral carcinomas from Sudanese snuff dippers (n=14) and oral carcinomas from Sudanese (n=14), Swedish (n=19) and Norwegian (n=41) non‐snuff dippers were examined by immunohistochemistry for expression of K types 13, 14 and 19 using monoclonal antibodies. HPV infection was searched for in all the carcinomas by in situ hybridization (ISH) using the cocktail HPV OmniProbe and the ViraType probe. Carcinomas from Sudanese (snuff dippers/non‐snuff dippers) were also examined for HPV infection by polymerase chain reaction (PCR) using the general HPV primers GP5+/GP6+. For the oral carcinomas from snuff dippers, moderate to intense expression of K13 (71%; 10/14), K14 (86%; 12/14) and K19 (93%; 13/14) was found. For the oral carcinomas from non‐snuff dippers, weak to moderate expression of K13 (64%; 47/74), K14 (43%; 32/74) and K19 (45%; 33/74) was found. HPV DNA was not detected in any of the carcinomas from three countries when examined by ISH. The Sudanese (from snuff dippers/non‐snuff dippers) oral carcinomas were also negative for HPV DNA with the PCR. The present study shows that (i) there is a high level of expression of K13, K14 and K19 in oral carcinomas from snuff dippers compared to those from non‐snuff dippers, (ii) this high level of expression may arise from dysregulation of keratinocyte proliferation and maturation caused by damaging effects of snuff, (iii) the HPV genome is not found in Sudanese (snuff dippers/non‐snuff dippers), Swedish or Norwegian oral carcinomas, and (iv) this may suggest that these viruses do not play a prominent role in the aetiology of oral carcinomas from these countries.

Laser conization of cervical intraepithelial neoplasia grade 3, Free resection margins indicative of lesion-free survival

BACKGROUND Various grades of cervical intraepithelial neoplasia may occur following laser conization for grade 3 lesions. The aim of this study was to assess lesion-free survival after laser conization in cases with/without free resection margins, and to test whether detection of human papillomavirus infection and/or p53 expression in the cone lesion were useful predictors of lesion-free survival. METHODS In 598 women treated for cervical intraepithelial neoplasia grade 3 the state of the resection margins was recorded and related to the findings on follow-up, up to 15 years post-operatively. Lesion-free survival times were analyzed by the Kaplan-Meier method. The presence/absence of human papillomavirus infection and/or p53 expression in the primary lesion was investigated in every fifth case by in situ hybridization and immunohistochemistry respectively. RESULTS Lesion-free survival was significantly more common after complete than incomplete excision of cervical intraepithelial neoplasia. In the latter, lesions tended to appear shortly after surgery, indicating the presence of residual disease. The few lesions appearing later were evenly divided between those with and those without complete excision. The results of the human papillomavirus and p53 investigations added no further information. CONCLUSIONS The presence of cervical intraepithelial neoplasia in the cone margin gives strong indication of potential treatment failure. In its absence laser conization is highly effective in the treatment of cervical intraepithelial neoplasia, and has the advantage of providing a specimen suitable for the necessary histological investigation.

Effervescence and Ephemerality: Popular Urban Uprisings in Mozambique

ABSTRACT This article analyses the large-scale popular urban uprisings that shook Mozambican cities on 1 and 2 September 2010, following the governments announcement of successive rises in the price of public transport fares and basic commodities. Using ethnographic material from the city of Chimoio and the capital Maputo, the following work highlights the organisational character of the ‘strikes’ (greves), as the popular uprisings were called, and explores them as a new form of organising political discontent. Comparing them to other historical and contemporary popular uprisings, this article argues that the strikes violently and rhizomically generated ephemeral and egalitarian forms of political authority and order that simultaneously confronted, replicated and undercut the aspects of Mozambican statehood. Deploying Durkheims notion of effervescence, the work further argues that the creative fervour, multisemic aspects and festive character of the popular uprisings need to be recognised; thus, this analysis challenges the reductive labelling of these events as ‘riots’ or ‘food riots’.

‘Entering the Red Sands’: The Corporality of Punishment and Imprisonment in Chimoio, Mozambique

This article probes the understandings and experiences of punishment and imprisonment in and around Chimoio, Manica Province, Mozambique. Focusing on two cases of imprisonment under severe conditions in the provincial agricultural prison of Chimoio, the article argues that corporal punishment is part of the punitive infrastructure of both the colonial and post-colonial state. Analysing the two contrasting cases, the article probes the significance of the metaphor for prison entry – ‘entering the red sands’ – to make the argument that carceral punishment is understood in terms of entry into a state space of potential death. The article recognises the importance of grounding perspectives on imprisonment and punishment beyond assumptions of universal regimes of imprisonment and punishment regimes. In doing so, it focuses on popular understandings and experiences of such practices and supports its argument by demonstrating, firstly, the long-term trajectory of corporal punishment in Mozambique and, secondly, by showing how imprisonment is perceived as challenging key tenets of sociality.

The cervical smear record: Its relevance to the subsequent development of cervical neoplasia

Background. Our aim was to investigate the previous smear history in women with cervical intraepithelial neoplasia grade 1–3 or squamous carcinoma and define its relevance to the lesion present in 1989.

Human papillomavirus infection in progressive and non‐progressive cervical intraepithelial neoplasia

Human papillomavirus (HPV) infection is common in cervical intraepithelial neoplasia (CIN) and is widely held to be responsible for its progression to grade 3. This thesis is examined here. Comparison of the level of HPV changes in 133 lesions that had not progressed to that in those from 197 women with histologically proven CIN 3 failed to reveal significant differences in their level of HPV infection on cytology, histology or in situ hybridization. However, in both these groups, some of the cases that did not show HPV positivity on in situ hybridization with probes reacting with the common HPV types did show evidence of HPV DNA using a general primer‐mediated polymerase chain reaction. This may indicate low‐copy number infections or non‐productive infections. Such reactions were more frequent in the women with progressive lesions, and it is probable that they may also have been at greater risk of cervical infection in general. The present findings suggest that a further factor, a co‐carcinogen, may be involved in progression to CIN 3, HPV being a common forerunner, providing a proliferative environment and thus favoring such an event.

1968 and its other worlds: Global events and (anti-)state dynamics in France, Mozambique and Vanuatu

ABSTRACT This article de-centres the moment, event and impact of 1968 and expands it temporally and spatially. Taking a longue durée approach charting a trajectory from the 1960s into the 1980s, we analyse statist and anti-statist dynamics through a comparison of the May 1968 Paris riots with the Nagriamel movement in Vanuatu and the phenomenon of Naparama in Mozambique. Such a horizontal triangulation and spatio-temporal expansion is undertaken to contribute to a more global understanding of what we term ‘the 1968 event’ entails. However, this comparative analysis also underlines how its impact should be measured as, first, an experimentation with and attack on political reality, second, how the intricate connections between Euro-American and other worlds were integral to its articulation and, third, how paradoxically 1968 and its response spawned the rise of an authoritarian form of nation-state – eclipsing the openings in the firmament of the political, social and the real afforded by the original event.

German Pentecostal Witches and Communists: The Violence of Purity and Sameness

This research investigates a commonly held view in certain peri-urban areas around Chimoio, Mozambique, that German Pentecostal pastors and missionaries, as well as German communists, have been operating as witches from the 1990s until the present time. Drawing on ethnographic material (1999–2016), the chapter explores the popular perception that these ‘Germans’ (alemaos) were promulgating an egalitarian value of sameness and an ethos of purity: gradually, however, they came to be regarded as witches, engaged in nocturnal bloodsucking and undertaking savage hunts for children who were subsequently kidnapped or devoured. Drawing on colonial era cases and comparing the material with other African as well as Melanesian cases, the chapter also relates these ideas about the violence of German witches to long-standing experiences of enslavement, domination and violence, which involve dynamics of memorialization common across both Africa and Melanesia.

Valuable Subversions: Gendered Generativity and Sorcerous Production in Central Mozambique

How is one to analyze the existence of a subterranean dwarfish couple (zwidoma) occupying the space underneath cooking places and whose central purpose is to reinforce a market woman’s sales—but simultaneously feeding off her very body? Using urban and rural ethnographic material from central Mozambique, where such assemblages comprising the zwidoma and a woman are integral to economic life and social orders, this article contextualizes such constellations—effectively interferences within various domains of value—by undertaking an analysis of gendered modalities of generativity. Further, by meditating on various understandings of cosmology and, ultimately, the dynamics constituting the realms of the real, it presents an alternative to influential analyses of capitalism, such as the notion of “occult economies.” An argument is made not only for value’s dynamic and changeable nature but also for the necessity to appreciate instances of its subversion with destructive effects. The article underlines, therefore, how such subversions of value, in various forms, is in line with Tsing’s (2015) general argument that critical explorations of capitalism and regimes of valuation and production are best undertaken in peri-capitalist zones—such as urban and rural Mozambique.