Low-grade squamous intraepithelial lesion co-infected with human papillomavirus and Chlamydia

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Human papillomavirus (HPV) is the most common sexually transmitted infection (STI) in the United States. The genital area, mouth and throat are most commonly affected. Research has shown that HPV is a cause of cervical cancer and Chlamydia trachomatis is a potential cofactor in the development of cervical intraepithelial neoplasia (CIN). However, only limited cases have been reported to understand this coinfection and its mechanism through the lens of molecular biology. We present a case of a 22-year-old woman with complaints of persistent lesions on the labia for more than 6 months that have been increasing in number. Histopathology suggested HPV. This case report emphasizes the importance of HPV and Chlamydia co-infection as major causes of persistence of condyloma acuminatum and low-grade squamous intraepithelial lesions (LSIL) and the importance of screening and clinical management of vaginal HPV.

introduction

Cervical pathologies that present abnormal cervical cells, whether precancerous or cancerous, are often associated with human papillomavirus (HPV). Most commonly, high-risk HPV such as HPV 16 and HPV 18 have been found to play a role in cervical epithelial cell transformation by inhibiting tumor suppressors such as TP53 and pRb [1]. Although HPV plays a major role in cervical dysplasia and carcinoma, there are other factors and events that lead to the development of dysplasia and cancer. One of these factors is the co-infection of Chlamydia trachomatis (C. trachomatis) which has the potential to disrupt the cervical epithelium and thus increase HPV persistence and increase the risk of dysplasia and neoplasia [2]. Its role in oncogenesis has been linked to its effect on inhibiting the mismatch repair pathway (MMR) and causing DNA breaks, which together can lead to uncontrolled proliferation [3]. This case study focuses on HPV and Chlamydia co-infection as a driving factor for the persistence of both condyloma acuminatum and low-grade squamous intraepithelial lesions (LSIL) at the molecular level.

case presentation

A 22-year-old woman with a history of polycystic ovary syndrome (PCOS) presented to the Family Medicine Clinic to establish care with a primary care physician. The patient complained of lesions around her labia that had been present for at least 6 months. She has never had a cervical exam and has never been tested for STDs in the past. Pelvic examination revealed multiple (>20) 1-2 mm wart-like lesions on the labia majora (Figure 1). At this time, the lesions were light brown, similar to the patient’s skin, soft, cauliflower-like and without discomfort such as pain, redness or itching. The rest of the physical examination was unremarkable. Papanicolaou (Pap) smear and screening specimens for sexually transmitted diseases (STIs) were collected.

The patient was positive for C. trachomatis Infection and cervical cytology led to LSIL. She was treated promptly C. trachomatis with doxycycline. The patient returned to the clinic for biopsy of the vulval lesions. Because of the LSIL diagnosis, an HPV sample was also taken at the time. The biopsy revealed that the culprit of the lesions was condyloma acuminatum. E6/E7 viral messenger RNA from 14 high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68) was not detected.

The patient was advised to return for another pap smear test in 6 months for LSIL with no high-risk HPV finding and to return earlier to discuss treatment of genital warts with trichloroacetic acid (TCA). When the patient returned, the lesions around the labia were spread bilaterally with no improvement in number or appearance; However, the patient complained of severe discomfort due to itching. She agreed to continue TCA treatment (Fig 2). The patient tolerated the first TCA treatment well. Several warts remained after treatment, but five larger warts reduced in size. The patient agreed to continue TCA treatment weekly and will be followed up for a Pap smear in 6 months.

Vulvar Lesions Immediately After First Trichloroacetic Acid (TCA) Treatment

discussion

C. trachomatis is a common sexually transmitted disease. Although it is easily treatable, it is often asymptomatic and causes damage to the female reproductive tract through the formation of scar tissue [4]. Not only can it cause such permanent damage, but it also has the potential to alter the cervical epithelium.

C. trachomatis affects the MMR pathway by inhibiting the expression of MMR genes [3]. The role of this pathway is to correct post-replication errors such as insertions or substitutions. When this pathway is defective, genomic stability cannot be maintained. This leads to microsatellite instability (MSI), which is associated with many types of cancer, including cervical cancer [5]. C. trachomatisMMR is inhibited via the proteasomal degradation of E2F1, a transcription factor. Such inhibition of this pathway is believed to promote mutation and hence oncogenesis [3].

The role of HPV in cervical pathology is well known and has played a role in current cervical screening practices. The American College of Obstetricians and Gynecologists (ACOG) recommends beginning screening with cytology only at ages 21 to 29. Between the ages of 30 and 65, one can have either cytology-only testing every 3 years, HPV only testing every 5 years, or HPV and cytology co-testing every 5 years [6]. Although many HPV infections can clear up on their own, co-infection with C. trachomatis has been shown to be a risk factor for HPV persistence [2,7].

However, C. trachomatis and other possible co-infections currently play no role in cervical cancer screening guidelines.

Our patient presented with diffuse and persistent vulvar warts, which were soon identified as condyloma acuminatum. During further evaluation, our patient was diagnosed C. trachomatis. Although the patient was determined to be negative for high-risk HPV types, cervical cytology revealed LSIL.

Conclusions

This case illustrates the role that C. trachomatis plays in cellular reprogramming. At a young age, HPV infection is expected to resolve on its own and poses a low risk of disease. However, this case demonstrated that when Chlamydia was co-infected, the patient’s HPV-related illness, even without evidence of high-risk HPV, resulted in persistent and numerous warts and a diagnosis of LSIL. Although the role of chlamydia in cellular reprogramming continues to be studied, this case supports current studies that such co-infection plays a role in disease. This should prompt doctors to frequently screen for chlamydia to treat it before it can play a role in cellular reprogramming and increase the risk of cervical and vulvar disease. Although it would be advisable to observe and examine patients with current or previous histories C. trachomatis For cervical cancer, more studies need to be done before new preventive guidelines are established.

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