SARS-CoV-2 RNA may rarely be present in a uterine cervix LBC sample at the asymptomatic early stage of COVID 19 disease.

OBJECTIVE: Currently, it is thought that uterine cervix mucosal samples present a low risk of SARS-CoV-2 exposure. So far, there is no evidence of SARS-CoV-2 detection in Papanicolaou (Pap) smears. Nevertheless, clinicians could be exposed unaware to the coronavirus while performing and handling a Pap smear. We aimed to retrospectively evaluate the presence of SARS-CoV-2 RNA in cervical liquid-based cytology (LBC) samples in women who tested positive for a nasopharyngeal COVID-19 PCR test. METHODS: From our laboratory database, we identified patients with data on a cervical cancer screening LBC sample paired with a positive nasopharyngeal COVID-19 PCR test. Relevant LBC samples taken within an incubation period of 14 days and post-onset RNA shedding interval of 25 days were subsequently tested for SARS-CoV-2 RNA using RT-PCR tests. RESULTS: The study group consisted of 102 women. Of those, 23 LBC samples were tested. SARS-CoV-2 RNA was detected in one LBC sample from a 26-year-old asymptomatic woman taken six days before reporting headaches and knee arthralgia with a positive nasopharyngeal SARS-CoV-2 RT-PCR test. CONCLUSIONS: It is possible to detect SARS-CoV-2 RNA in cervical LBC samples at an early asymptomatic stage of COVID-19. In general, this finding is infrequent in asymptomatic women who tested SARS-CoV-2 positive within an incubation of 14 days and a post-onset RNA shedding period of 25 days. We fully support the current thinking that cervical LBC samples from asymptomatic women pose a low risk of SARS-CoV-2 exposure and can be handled in the frame of good microbiological practice and procedures.

The newly proposed International Endocervical Adenocarcinoma Criteria and Classification and its relevance to cervical cytology screening assessed in a prospective 2-year study of 118 cases.

BACKGROUND: It is generally acknowledged that interobserver variability for the histological diagnosis of endocervical adenocarcinoma (EA) subtypes is suboptimal. The recently proposed International Endocervical Adenocarcinoma Criteria and Classification (IECC) system is based on the presence of associated human papilloma virus (HPV) infection. It recognises HPV-associated EAs and non-HPV-associated EAs. METHODS: This prospective cytology-histology and molecular genetics-based study investigated the potential effect of IECC being applied to Papanicolaou (Pap) test with regard to the diagnostic accuracy of severe glandular lesions reported at least as adenocarcinoma in situ (AIS). RESULTS: Out of 118 liquid-based cytology Pap tests with AIS+ lesion, complete information on follow-up biopsy and HPV status was available in 51 cases. AIS and EA category correlated with histologically confirmed AIS/EA in 88.5% (23/26) and 70.5% (12/17) of cases, respectively. Interestingly, 93% (40/43) of cases diagnosed as AIS/EA were HPV positive and 7% (3/43) were HPV negative (originating in the cervix, endometrium and adnexa). CONCLUSIONS: Our findings suggest that this approach could possibly divide Pap tests containing severe glandular lesion into two groups: (a) robust diagnosis of HPV-associated EA and (b) non-HPV associated glandular lesions of heterogeneous origin, requiring further clinical preoperative diagnostic workup.

The detection of DNA methylation of tumour suppressor genes in cervical high-grade squamous intraepithelial lesion: A prospective cytological-histological correlation study of 70 cases.

BACKGROUND: DNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa-miR-124 genes in high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) samples with a histological correlation. METHODS: Seventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3-month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in-house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa-miR-124 was performed by multiplex methylation-specific real-time polymerase chain reaction. RESULTS: A positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied. CONCLUSION: The DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi-infection.