A wolf in sheep's clothing: HPV-negative cervical cancer

Author: Chen Yongning, attending physician of the First Affiliated Hospital of Jinan University

Reviewer: Gong Shipeng, Chief Physician, Nanfang Hospital, Southern Medical University

"Have you ever had a human papillomavirus (HPV) test? Have you received the HPV vaccine?" As people's awareness of health care and physical examinations increases, female friends often mention HPV in daily conversations. We all know that HPV is an important cause of cervical cancer. When people get a positive HPV test result, they often start searching online, and the results often make people panic. There are often jokes about "cervical cancer per capita" on the Internet, which has led to a lot of excessive examinations and treatments. A negative result makes people feel relieved temporarily.

Does a negative HPV mean you won't get cervical cancer? Obviously not. There is another rare type of cervical cancer, namely HPV-negative cervical gastric adenocarcinoma. It is like a wolf in sheep's clothing, easily deceiving many gynecologists and pathologists. Cervical gastric adenocarcinoma is very cunning. Unlike other common cervical cancers that have irregular vaginal bleeding and contact bleeding as typical symptoms, most of them are mainly vaginal discharge and increased leucorrhea, and are often misdiagnosed as common gynecological diseases. The surface of the cervix is ​​basically smooth, and most of the lesions are located deep in the cervical canal. Conventional cervical scrapings are easily missed, and HPV is negative, making it even more difficult to detect. Even if a tumor is removed by biopsy or cervical canal scraping, its morphology under the microscope is not much different from normal cervical cells, and it is very easy to be misdiagnosed as normal.

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Ms. Li, 51 years old, recently went to the local hospital for an outpatient examination due to increased watery leucorrhea and repeated lower abdominal pain. The HPV test was negative, and the cervical liquid-based cytology (TCT) was normal. Only B-ultrasound indicated that the cervical canal was thickened. Subsequently, a colposcopy biopsy was performed, and multiple points on the appearance of the cervix and the cervical canal scraping tissue were considered to be chronic cervicitis. Because the problem could not be solved, the patient visited the doctor again. After another biopsy, cervical canal scraping and communication with the pathology department, it was finally diagnosed as adenocarcinoma. After admission, the magnetic resonance imaging showed that there was a tumor of about 3 cm in the cervical canal. Because it was in the early stage, the common adenocarcinoma tumor markers CA199, carbohydrate antigen 125 (CA125), and carcinoembryonic antigen (CEA) were all normal. After surgical treatment, the lymph nodes have not yet metastasized. Although it is in the early stage, due to the special pathological type, accompanied by medium-risk factors such as adenocarcinoma, large mass, and infiltration of the outer 1/3 muscle layer, he also received radiotherapy and chemotherapy after surgery and is currently tumor-free.

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The age range of onset of cervical gastric adenocarcinoma is wide, and young women to elderly women may be affected, especially patients with Peutz-Jeghers syndrome have a higher risk of disease. Peutz-Jeghers syndrome, also known as hereditary mucosal pigmented gastrointestinal polyposis, is a clinically rare autosomal dominant genetic disease and a hereditary colorectal cancer. It is divided into two parts. One is the pigmentation of the lips, mouth, eyes, nose, fingertips, palms, heels, perianal area, etc., among which the pigment spots on the lower lip are the most obvious; the other is the gastrointestinal hamartoma polyps, which are prone to complications such as intussusception and intestinal obstruction. These patients have a higher risk of developing various types of cancer than ordinary people. Female patients should pay special attention to the risk of gynecological malignancies. If necessary, STK11 gene testing should be performed to determine whether Peutz-Jeghers syndrome exists.

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Considering that the symptoms of cervical gastric adenocarcinoma are atypical, TCT and HPV tests are often negative, and it is not easy to be detected. We recommend:

(1) Women who have sex should undergo TCT examination at least every 3 years or HPV test every 5 years. If there are any abnormalities, they should seek medical attention in time and the doctor will assess whether further examination is needed.

(2) Testing for tumor markers during physical examinations is also of certain significance. About half of patients with cervical gastric adenocarcinoma have elevated CA199, and about one-third have elevated CA125. Elevated CA125 often indicates the presence of pelvic and abdominal metastasis. A small number of patients have elevated serum CEA.

(3) HPV-negative results should not be taken lightly. If there is any abnormal vaginal discharge, it should be taken seriously and medical attention should be sought promptly. If the cause cannot be found or the treatment is ineffective, it is recommended to see several doctors, including experts in gynecology, oncology and other fields. Early detection and early treatment can achieve good results.