Human Papilloma Virus (HPV): Screening Tests

Human Papilloma Virus (HPV) is a DNA virus of which more than 200 types have been determined (Figure-1). Although there is direct or indirect transmission from contaminated surfaces, skin lesions and birth canal, the most important one is sexually transmitted. There are about 60 types causing infections in humans. Although the genital tract infections have the most clinical significance; the other localizations such as skin, eyes, nose, mouth, and trachea are also seen.

The main importance of HPV is that it is the causative agent of more than 99% of cervical cancer, which is common among female cancers and is among the cancers that cause the most deaths. About 90% causative agents of genital warts are types 6 and 11, which are in the low risk group in terms of cancer. Whereas, types 16, 18, 31, 33, 45, 52 and 58, which are in the high risk group, are held responsible for the development of cervical cancer by 90%. In addition to cervical cancer, the types specified as high-risk HPV types in terms of cancer play an important role in the development of various cancers, including vaginal, vulvar, anal, penile and oropharyngeal carcinoma.

Figure-1: General schematic structure of HPV (type-16 is given here)

HPV types 16 and 18 (these two types are the causative agent of 70% of cervical cancers) and types such as 31, 33, 35, 39, 45, 51, 56, 58, 59, 68, 73 and 82 are considered in the high-risk group. Types 6 and 11 (these two types are the cause of 90% of genital warts), 40, 42, 43, 44, 54, 55 and 62 are among the low risk groups.

Can Cervical Cancer Be Prevented?

There is no drug that destroys the HPV virus and treatment is aimed at removing the lesions. If HPV warts are not treated, the warts may remain the same, grow, or may occur regression/complete disappearing spontaneously.

Fortunately, an important feature of cervical cancer is that it is preventable with the implementation of appropriate vaccination and screening programs. Therefore, screening programs for HPV and vaccine planning according to regional characteristics is of great importance. There are three types of HPV vaccines that have been approved so far:

Table-1: Approved HPV vaccines and ingredients, *Not available in Turkey

All three types of the vaccines protect against HPV types 16 and 18 that cause most HPV cancers. The nine-valent HPV vaccine is the only HPV vaccine currently distributed in the U.S.

From the Table-1, it can be predicted that 70% of cervical cancers can be prevented with the bivalent vaccine. Whereas, 70% of cervical cancers as well as 90% of genital warts can be prevented by the quadrivalent vaccine. It can be predicted that 85% of cervical cancers and 90% of genital warts can be prevented by the nine-valent vaccines, which are not available in our country.

Cervical Cancer Screening and Its Importance

In the clinical stage, HPV infection can be diagnosed by visual examination of the existing lesions. Subclinical infections can be detected during Pap smear examinations or routine screening examinations. However, due to the fact that the evaluation for Pap smear requires expertise and is not based on objective criteria, it is not sufficient without another supporter criteria. Especially in the case of latent asymptomatic HPV infection, the diagnosis can only be made by demonstrating viral nucleic acids in the tissue or cells at the infection site.

As mentioned above, not all HPV types have the same clinical significance. Therefore, besides screening the agent, typing is also of great importance.

Pap smear and molecular tests have an indispensable place in screening. Because, on the one hand, the vast majority of HPV infections are temporary, on the other hand, the degree of clinical significance differs between the types. For this reason, screening algorithms have been developed according to the patient’s condition.

HPV Screening Tests

HPV screening tests can be performed for the prediction of cervical cancer, as well as for follow-up after abnormal Pap smear and even for oropharyngeal cancer treatment planning. Because the paths to be followed in HPV positive and negative cancer treatments are different.

Tests that can be used in HPV follow-up generally give priority to the screening of certain types in order to reveal clinically important types first:

1. HPV DNA Tests: With this method, besides showing whether the virus is present in the sample taken, it is also possible to detect certain types (Figure-2).

Figure-2: A DNA test study that detected 28 HPV types (19 high, 9 low risk) in a single study (also used by Denge Laboratory)

2. HPV RNA Tests:  Ongoing infections are the main cause of cervical cancer. These tests determine the risk of development of cervical carcinoma and dysplastic pre-stages by detecting E6/E7-mRNA oncogenes.

3. Cellular Marker Tests: Instead of the genetic material, these kind of tests look for evidence of two proteins, elevated in cell samples that are infected with the HPV virus, called p16 and Ki-67.

References: (Access: 02.11.2021)

Kadıoğlu BG, Tanrıverdi EÇ, Alay H, Uçar M. Mikrobiyol Bul. 2018 Oct;52(4):367-375. doi: 10.5578/mb.67419.

Şahiner F. Genital İnsan Papillomavirus Enfeksiyonlarının Moleküler Tanısında Karşılaşılan Sorunlar ve Yeni Gelişmeler. Mikrobiyol Bul 2014; 48(4): 689-706 (Access: 02.11.2021) (Access: 02.11.2021)