I. What is cervical cancer?

As the most common malignant tumor in the female reproductive system, cervical cancer is the leading cause of death in women.

According to the World Health Organization (WHO) report, in 2020 alone, an estimated 604,000 women worldwide were diagnosed with cervical cancer, and about 342,000 women died of the disease. Cervical cancer is the most common cancer in 23 countries worldwide and the leading cause of death by cancer in 36 countries. 

The incidence of cervical cancer in China is quite high. In 2018, 106,430 new cases and 47,739 deaths by cervical cancer were reported in the country, accounting for 18.2 percent and 17.3 percent of global cervical cancer incidence and mortality, respectively. In recent years, the incidence of this cancer in China has significantly increased, especially in younger people. The number of cases has increased at a rate of 2-3 percent every year. Persistent high-risk human papillomavirus (HPV) infection is the main cause of cervical intraepithelial neoplasia and cervical cancer. 

Cervical cancer is currently the only human cancer with a clear etiology and can be prevented at an early stage, treated and completely eradicated. The five-year survival rate with early treatment is almost 100 percent, but only 20-50 percent with late treatment.

Early screening of healthy people and early diagnosis of unhealthy people are the main ways to prevent the occurrence and development of cervical cancer.

II. What is HPV?

HPV is divided into high-risk and low-risk categories, and the main cause of cervical cancer is a persistent infection of high-risk HPV, which means that the same type of HPV can be detected on two HPV aetiological tests at least 12 months apart. 

In addition, different types of HPV infections can cause different diseases:

Persistent infection of high-risk HPV can cause precancerous lesions and invasive cancers in body parts such as the cervix, vagina, vulva, anus, penis, head and neck.

Infection of low-risk HPV can cause benign diseases such as skin warts, anogenital warts, and recurrent respiratory papillomas.

III. How does HPV spread?

1. Sexual transmission: This is the most common way it is transmitted.

2. Mother-to-child transmission: Neonates are infected during childbirth, such as recurrent respiratory papillomas in children.

3. Skin mucous membrane contact: Contact via the oral cavity, throat, skin and anus in addition to the cervix.

IV. Development of HPV infection

Cervical infection with HPV is mostly transient, and most HPV infections do not cause abnormal cell morphology.

About 30 percent of HPVs in the free state will produce corresponding cytopathological changes, causing low-grade squamous intraepithelial lesions. But they are not precancerous lesions, and the natural course of the disease tends toward spontaneous clearance.

Persistent infection of high-risk HPV increases the probability of HPV and human DNA integration, and about 10 percent of infections will progress to high-grade squamous intraepithelial lesions – the precancerous stage. Lesions usually stay for a long time at this stage, and the most important part of cervical cancer screening is the detection of high-grade squamous intraepithelial lesions, after which treatment will be given.

V. Common HPV screening methods

1. Hybrid Capture 2 (HC-2): Regarding the second generation of hybrid capture assay, or HC-2, the Kaiser Permanente Medical Center in the United States has more than 1 million pieces of clinical validation data, and Science Citation Index (SCI) literature has published more than 10 million pieces of clinical research data. The "full-length cocktail" probe technique covers all regions of HPV DNA. The new generation of HC-2 can detect 14 types of high-risk HPV DNA. It is the current gold standard for HPV clinical detection, with a sensitivity of nearly 97 percent and a negative predictive value of 99.96 percent.

2. HPV E6/E7 mRNA detection: This method features high specificity. A positive result means that HPV is in an integrated state and has a high risk of developing into cervical precancerous lesions and invasive cancer. Without intervention, it will definitely lead to cancer. Therefore, the detection of HPV E6/E7 mRNA can avoid unnecessary psychological distress caused by the transient positive result brought by the single detection of HPV DNA.

3. HPV capsid protein detection: This method features high sensitivity and specificity. A positive result indicates HPV infection, but with a good prognosis. A negative result means there is no HPV infection or there is an HPV infection with a poor prognosis.

4. PCR polymerase chain reaction-HPV typing test: This method can identify the type of HPV infection. Advantages: (1) The pathogenic risks of different types of HPVs are different, and typing can better guide diagnosis and treatment; (2) Typing helps to determine whether the same type of HPV causes persistent infection, which helps with risk assessment. Disadvantages: Certain false negatives and false positives may occur for various reasons, such as the high requirements for the laboratory, the primer design region (such as the L1 region) may be lost, and DNA extraction and nucleic acid amplification are required.