HPV is a 55 nm in diameter, non-enveloped double-stranded DNA virus that infect epithelial cells such as those in the skin and mucous membranes.8 HPV, multiplies in the nucleus as an episome, and is primarily found in the cytoplasm in that form.9 HPV genome is a circular DNA double-stranded chain of about 8 kb, an open reading frame (ORF) is applied to the transformation of its DNA replication and E1, E2, E4, E5, E6, E7 genes.9 More than 150 different types of HPV have been confirmed till today and among these 60 types have genotypes which can cause infection of the human genital organs. About one in four women will get infected with the types of HPV that are related to cervical cancer in their lifetime, although most of the HPV infected people do not have any signs.10 HPV is classified into three groups according to its carcinogenic potential; high-risk (HR), probable HR, low-risk (LR).11 Genotypes that belong to the HR group are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 types, and genotypes that belong to the probable HR group are 26, 53, and 66 types, and genotypes that belong to the LR group are 6, 11, 40, 42, 43, 44, 54, 61, 70, 72, and 81 types.10 Nearly all cases of cervical cancer are caused by infection with oncogenic or HR type of HPV. HPV types 16 and 18 have been found in 70% of cervical cancer patients around the world. LR HPV types are commonly detected in genital warts.10 These sexually transmitted HPV viruses also cause most of the anal cancers; many vaginal, vulvar, and penile cancers; and some oropharyngeal cancers.10 Although HPV infection is very common, most infections will be suppressed by the immune system within 1 to 2 years without causing cancer.11 If a cervical infection with a HR HPV type persists, the cellular changes can eventually develop into more severe precancerous lesions.12 If precancerous lesions are not treated, they can progress to cancer.13 It can take 10 to 20 years or more for a persistent infection with a HR HPV type to develop into cancer.14 Persistent HPV infection has been found to be the main cause of cervical cancer.4

Precancerous lesion of cervical cancer can be cured in 98% of patients.15 Once cancer develops or transition occur the five-year survival rate is 20%. Cervical cancer is more important than the lesions detected early through regular screening. Currently in Korea, the primary screening test for cervical cancer is the Pap test for observing the cells scraped off the uterine cervix, but traditional Pap smear has limitations in terms of sensitivity and specificity. A discussion about the need for the HPV test is becoming active in order to compensate for the limitation of cytology. Screening guidelines for HPV test in Korea stated that women younger than 30 years should not be screened because of the high false positive rate and infection clearance rate of HPV test (Table 1). In women more than 30 years of age, HPV test cannot replace cytology, but co-testing (cytology and HPV test) is recommended because it can yield a false negative cervical cytology. In women with HR HPV types 16 and 18 in whom a normal Pap smear was obtained, the probability of developing precancerous cervical lesions is 35 times higher.16

Many methods have been developed for molecular detection of HPV. Among HPV tests, only 5 HPV detection methods were approved by the FDA in United States until the year 2015.17 These five HPV tests include 3 polymerase chain reaction (PCR) tests, HPV E6/E7 RNA test, and HPV DNA chip test.

The Korean HPV screening guidelines, stated that HPV test cannot replace cytology. However, co-testing (cytology and HPV test) is recommended because it can yield a false negative cervical cytology when used alone (Table 1). In our country, all women more than 30 years of age undergo cytology without any cost every two years for national insurance. Although physicians are aware of the importance of the HPV DNA test, the public is still not aware of its importance; hence, primary screening with the HPV test is restricted and limited. The application of the test for detecting HR HPV types has allowed clinicians to identify women at highest risk of cervical cancer more accurately and earlier during the progression of the disease.17 Cytology, while valuable, merely detects abnormal cellular changes which may be the consequences of HPV infection or possibly inflammation.22 HPV DNA testing is less subjective and more sensitive in detecting precancerous lesion than cytology alone, particularly for the detection of adenocarcinoma precursors. In a systematic evidence review of randomized studies conducted for the U.S. Preventive Services Task Force, HPV DNA testing was found to demonstrate an average of 35.7% greater sensitivity than cytology in the detection of CIN2 or CIN3.17 Based on these data, it should come as no surprise that the potential benefit of HPV DNA testing have been recognized in the U.S. guidelines, to help clinicians identify and triage women at the highest immediate risk of high-grade cervical disease.15 Lesions more than CIN2 in post-menopausal women are not recognized by a single Pap smear, but a large fraction of pre-invasive cervical cancer cases in post-menopausal women result from infections by HPV types.23 There is no difference in the screening tests according to the menopausal condition. The HR HPV test was three times as sensitive as the Pap test in detecting grade 2 and 3 CIN lesions in women aged 50 to 65 years.24 Postmenopausal women are infected with persistent oncogenic HPV at a substantial rate, supporting the need for continued screening in postmenopausal women to detect pre-neoplastic genital lesions.25 In postmenopausal women, cervical cancer primary screening with HPV test show various results, but cervical cancer screening can help to determine future directions of the HR treatment. The major cause of cervical cancer is HPV, and early diagnosis and early treatment are possible, and it is a possibly curable disease. Cervical cancer screening guidelines differ from country to country, but cervical cancer prevention and early detection is done through the national support programs. Current guidelines recommend that all women 21 years or older with atypical squamous cells of undetermined significance (ASCUS) cytology should be tested for HR HPV, and that only those women with ASCUS who are positive for HR HPV should be referred for colposcopy.15 Also, in women aged 30 to 65 years, co-testing using the combination of Pap cytology plus HPV DNA testing is the preferred cervical cancer screening method.15 In Korea, women aged more than 20 years, Pap test is recommended every year.26 After the role of HPV in cervical cancer was identified, the importance of HPV detection test as a screening test was emphasized. Several tests have been developed and each test has its own advantages and disadvantages, and a new test method to overcome the disadvantages is still being developed. As the main aim of cervical cancer screening is to prevent morbidity and mortality from cervical cancer, the ideal screening test should be able to identify cervical cancer precursors likely to progress to invasive cancer, while minimizing unnecessary treatment for LR types. Today's guidelines aim to do that, while balancing varying levels of risk for women of different ages and encouraging clinicians to make recommendations based on individual patient histories. Today's guidelines and tests are those you would choose from among the large number of cervical cancer screening guidelines and tests, based on consideration that the selected guidelines and tests are effective. According to the menopausal condition, there is no difference in the screening tests for cervical cancer, and HPV test can help to determine future directions of the HR treatment. But, how it will recommend the HPV test as cervical cancer screening? The choice of tests will depend upon you.

In conclusion, HPV test can be used in cervical cancer screening. Also, depending on the HPV DNA test results may be further performed cytology and colposcopy.