Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical int

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Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report Shiho Fukui1, Kazunori Nagasaka1* , Naoko Iimura1, Ranka Kanda1, Takayuki Ichinose1, Takeru Sugihara1, Haruko Hiraike1, Shunsuke Nakagawa2, Yuko Sasajima3 and Takuya Ayabe1

Abstract Background: Stratified mucin-producing intraepithelial lesion (SMILE) is a rare precursor lesion in the uterine cervix that is considered a variant of adenocarcinoma in situ (AIS). Although human papillomavirus (HPV) is thought to be related to the development of SMILE, there is little information available on the detection of HPV integrated into the lesion. Case presentation: A 30-year-old female underwent a routine uterine cervical cancer screening, and her Pap smear indicated the possible existence of atypical glandular cells. A cervical biopsy with endocervical curettage was performed. The histopathological analysis showed that she had SMILE and high-grade squamous intraepithelial lesion (HSIL) on her cervix. The lesion was found to be positive for HPV genotypes 52 and 68 by multiplex PCR. In situ hybridization with HPV RNA probes revealed that these HPV types were involved in the onset of HSIL and SMILE, respectively. Conclusions: Rare, high-risk HPV genotypes may contribute to the development of SMILE, and their detection can be useful for preventing the progression to carcinoma and ensuring adequate patient management. Keywords: Stratified mucin-producing intraepithelial lesion, Cervical intraepithelial lesion, Cancer stem cell, Human papillomavirus

Background Uterine cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer death among women in developed countries [1]. Although cervical screening including the human papillomavirus (HPV) test has reduced the incidence and mortality rate of cervical cancer worldwide [2], there is still little information about the role of less prevalent and rare HPV genotypes, such as HPV68, during cervical carcinogenesis [3]. Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix [4]. It is thought to arise from the reserve cells of the transformation zone throughout the full epithelial * Correspondence: [email protected] 1 Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan Full list of author information is available at the end of the article

thickness of a lesion, with some overlap with the architecture of squamous intraepithelial lesion (SIL) or adenocarcinoma in situ (AIS) [4]. SMILE is characterized by several histopathological features, including epithelial stratification, diffuse mucin production throughout the epithelial layers, and an absence of classic gland formation [5]; nuclear atypia, hyperchromasia, mitosis, and apoptotic bodies are often observed in the lesion, which is similar to other forms of intraepithelial neoplasia including usualtype AIS of the en